MXPA97001789A - Antiviral nucleosid analogues containing a substitute benzymidazole base united to a carbocicl ring - Google Patents

Abstract

The antiviral nucleoside analogs contain a substituted benzimidazole base attached to a carbocyclic ring in place of the conventional sugar residue. In formulas (I) and (I-1), R1 is H, CH3, or CH2OH, R2 is H or OH, R3 is H or OH, or R2 and R3 together form a bond, R4 is amino, cyclopropylamino, cyclobutylamino, isopropylamino , terbutylamino, or -NR8R9, where R8R9, together with the nitrogen atom to which they are attached, form a heterocyclic ring of 4, 5, or 6 members, R5 is H, and R6 and R7 are Cl, excluding the compound (+ -) - (1R *, 2S *, 3S *, 5S *) - 5- [5,6-dichloro-2- (cyclopropylamino) -1H-benzimidazol-1-yl] -3- (hydroxymethyl) -1, 2 -cyclopentanediol, and in the understanding that at least one of R1, R2, and R3 is or contains OH. The compounds have activity against infections by herpes virus, especially cytomegalovirus, and also by hepatitis virus

Description

ANALOGUES OF NUMBERS IDEALS THAT CONTAIN A SUBSTITUTED BENZYMIDAZOLE BASE LINKED TO T N. CARBYCLICAN The present invention relates to certain purine nucleoside analogs containing a carbocyclic ring in place of the sugar residue, to pharmaceutically acceptable derivatives thereof, and to their use in medical therapy, particularly for the treatment of certain viral infections. Hepatitis B virus (HBV) is a virus that contains a small DNA that infects humans. It is a member of the class of closely related viruses known as the hepadnaviruses, each member of which selectively infects either mammalian or bird hosts, such as the marmot and the duck. Throughout the world, the hepatitis B virus is a viral pathogen of great consequence. It is more common in Asian countries, and prevails in Sub-Saharan Africa. The virus is etiologically associated with primary hepatocellular carcinoma, and is thought to cause 80 percent of the liver cancer in the world. In the United States, more than ten thousand people are hospitalized for hepatitis B virus disease each year, and an average of 250 die with the fulminating disease.

The United States currently contains an estimated group of 500,000-1 million infectious carriers. Chronic active hepatitis develops in more than 25 percent of carriers, and often progresses to cirrhosis. It is estimated that 5,000 people die of cirrhosis related to hepatitis B virus each year in the United States of America, and that perhaps 1000 die of liver cancer related to hepatitis B virus. Even when there is a universal vaccine against the virus of hepatitis B, the need to have effective compounds against the hepatitis B virus will continue. The erratic pool of persistently infected carriers, estimated at 220 million worldwide, will not receive a benefit from vaccination, and will continue to be at high risk. Liver disease induced by the hepatitis B virus. This carrier population serves as the source of infection of susceptible individuals, perpetuating the disease instance particularly in endemic areas or in high risk groups, such as drug addicts IV and Homosexuals Accordingly, there is a need for effective antiviral agents, both to control chronic infection, and to reduce progress to hepatocellular carcinoma. The clinical effects of infection with hepatitis B virus are headache, fever, malaise, nausea, vomiting, anorexia, and abdominal pain. The replication of the virus is normally controlled by the immune response, with a course of recovery that lasts for weeks or months in humans, but the infection can be more severe, leading to chronic persistent liver disease, as mentioned above. In "Viral Infections of Humans" (second edition, Ed., Evans, A.S. (1982) Plenum Publishing Corporation, New York), Chapter 12 describes in detail the etiology of viral hepatitis infections. Of the .DNA viruses, the herpes group is the source of many viral diseases common in man. The group includes cytomegalovirus (CMV), vi cus Epstein-Barr (EBV), varicella zoster virus (VZV), herpes simplex virus (HSV), and human herpes virus 6 (VHH6). In common with other herpes viruses, infection with CMV leads to a long-lived association of virus and host, and after a primary infection, the virus can spread over a number of years. The clinical effects are from the death and disease of great magnitude (microcephaly, hepatosplenomegalea, jaundice, mental retardation) to poor development, susceptibility to infections of the chest and ears, and even a lack of any obvious disease effect. Infection with CMV in AIDS patients is a predominant cause of mortality, since 40 to 80 percent of the adult population is present in a latent form, and can be reactivated in immunocompromised patients. EBV causes infectious mononucleosis, and is also suggested as the causative agent of nasopharyngeal cancer, immunoblastic lymphoma, Burkitt's lymphoma, and hairy leukoplakia. VZV causes chickenpox and chicken shingles. Chickenpox is the primary disease produced in a host without immunity. In young children, it is usually a mild disease characterized by vesicular itching and fever. Herpes is the recurrent form of the disease that occurs in adults who were previously infected with chickenpox. The clinical manifestations of herpes include neuralgia and a vesiculeir itching of the skin that is of a unilateral and dermal distribution. The extent of the inflammation can lead to paralysis or convulsions, and it can occur, if the meninges are affected. In immunodeficient patients, VZV can spread, causing serious illness or even death. HSV 1 and HSV 2 are some of the most common infectious agents in man. Most of these viruses can persist in the neural cells of the host. Once infected, individuals are at risk of a recurrent clinical manifestation of infection, which can be both physically and psychologically disruptive. Infection with HSV is often characterized by extensive lesions of the skin, mouth, and / or genitals. Primary infections may be subclinical, although they tend to be more severe than infections of individuals previously exposed to the virus. Eye infections due to HSV can lead to keratitis or cataracts. Infection in the newborn, in immunocompromised patients, or penetration of the infection in the central nervous system, can be fatal. VHH6 is the causative agent of roseola infantum (exanthum subitum) in children, which is characterized by fever and the appearance of rash after the fever has declined. VHH6 has also been implicated in syndromes of fever and / or skin rash and pneumonia or hepatitis in immunocompromised patients. It has now been found that certain substituted benzimidazole compounds, as referred to below, are useful for the treatment or prophylaxis of certain viral infections. In accordance with a first aspect of the present invention, novel compounds of the formulas (I) and (1-1) are provided: wherein: R1 is H, CH3, or CH2OH; R2 is H or OH; R3 is H or OH; or R2 and R3 together form a bond; R 4 is amino, cyclopropylamino, cyclobutylamino, isopropylamino, terbutylamino, or -NR 8 R 9, wherein R 8 and R 9, together with the nitrogen atom to which they are attached, form a 4, 5, or 6 membered heterocyclic ring; R5 is H, and R6 and R7 are Cl, excluding the compound (+) - (IR *, 2S *, 3S *, 5S *) -5- [5,6-dichloro-2- (cyclopropylamino) -1H-benzimidazole -1-yl] -3- (hydroxymethyl) -1,2-cyclopentanediol, and provided that at least one of R1, R2, and R3 is or contains OH. The preferred compounds of the formulas (I) and (I-1) are those wherein R 4 is cyclopropylamino, isopropylamino, or terbutylamino, and especially, isopropylamino or terbutylamino. Preferred compounds of the formulas (I) and (I-1) are those of the formulas (IA) or (IA-1) wherein R2 is H or OH; R 4 is amino, cyclopropylamino, isopropylamino, terbutylamino, especially isopropylamino or terbutylamino, or -NRβR 9, wherein R 8 and R 9, together with the nitrogen atom to which they are attached, form a 4, 5, or 6 membered heterocyclic ring; Rs is H; and R6 and R7 are Cl, and excluding the compound (+) - (IR *, 2S *, 3S *, 5S *) - 5- [5,6-dichloro-2- (cyclopropylamino) -1H-benzimidazole-1- il] -3- (hydroxymethyl) -1,2-cyclopentanediol, and pharmaceutically acceptable derivatives thereof. Particularly preferred compounds of formulas (IA) and (IA-1), are those wherein R 4 is cyclopropylamino, isopropylamino, or terbutylamino; R5 is H; and R6 and R7 are both Cl; and the pharmaceutically acceptable derivatives thereof. It should be understood that the present invention encompasses the particular enantiomers illustrated in formulas (I) and (1-1), including purine tautomers, alone and in combination with their mirror image enantiomers. The enantiomers illustrated by formula (I) are preferred, and are preferably provided substantially free of the corresponding enantiomer, to the extent that it is generally mixed with less than 10 weight percent / weight, preferably less than 5 percent in weight / weight, more preferably less than 2 weight percent / weight, and most preferably 1 weight percent / weight of the corresponding enantiomer, based on the total weight of the mixture. The enantiomers illustrated by the formula (1-1) are more preferred, and are preferably provided substantially free of the corresponding enantiomer, to the extent that it is generally mixed with less than 10 weight percent / weight, preferably less than 5 percent by weight / weight, more preferably less than 2 percent by weight / weight, and most preferably less than 1 percent by weight / weight of the corresponding enantiomer, based on the total weight of the mixture. Particularly preferred examples are: (IR, 2S,; 3S, 5S) -5- [5,6-dichloro-2- (cyclopropylamino) -lH-benzimidazol-1-yl] -3- (hydroxymethyl) -1,2-cyclopentanediol; (+) - (l *, 2S *, 3S *, 5S *) - 5- [5,6-dichloro-2- (isopropylamino) -lH-benzimidazol-1-yl] -3- (hydroxymethyl) -1, 2-cyclopentanediol; (IR, 2S, 3S, 5S) -5- [5,6-dichloro-2- (isopropylamino) -1H-benzimidazol-1-yl] -3- (hydroxymethyl) -1,2-cyclopentanediol. (IR, 2S, 3S, 5S) -5- [2- (tert-butylamino) -5,6-dichloro-lH-benzimidazol-1-yl] -3- (hydroxymethyl) -1,2-cyclopentanediol; and (+) - (IR *, 2S *, 3S *, 5S *) -5- [2- (terbutylamino) -5,6-dichloro-lH-benzimidazol-1-yl] -3- (hydroxymethyl) -1 , 2-cyclopentanediol; (SS, 2R, 3R, 5R) -5- [5,6-dichloro-2- (isopropylamino) -1H-benzirtidazol-1-yl] -3- (hydroxymethyl) -1,2-cyclopentanediol; (SS, 2R, 3R, 5R) -5- [2- (tert-butylamino) -5,6-dichloro-lH-benzimidazol-1-yl] -3- (hydroxymethyl) -1,2-cyclopentanediol; (+) - (lR *, 2S *, 3S *, 5S *) - 5- [5,6-dichloro-2- (l-acetidinyl) -lH-benzimidazol-1-yl] -3- (hydroxymethyl) - 1,2-cyclopentanediol; (1 R, 2S, 3S, 5S) -5- [5,6-dichloro-2- (l-acetidinyl) -lH-benzimidazol-1-yl] -3- (hydroxymethyl) -1,2-cyclopentanediol; Y (1S, 2R ,, 3R, 5R) -5- [5,6-dichloro-2- [1-acetidinyl) -1H-benzimidazol-1-yl] -3- (hydroxymethyl) -1,2-cyclopentanediol; and pharmaceutically acceptable salts thereof.

The compounds of the formulas (I) and (1-1) above, and their pharmaceutically acceptable derivatives, are referred to herein as the compounds according to the invention. In a further aspect of the invention, the compounds according to the invention are provided, for use in medical therapy, particularly for the treatment or prophylaxis of viral infections, such as viral herpes infections. To date, the compounds of the invention have been shown to be active against infections by hepatitis B virus (HBV) and cytomegalovirus (CNV), although the first results suggest that the invention could also be active against other herpes virus infections. , such as VEB, VZV, VHSI and II, and VHH6. The compounds of the present invention are particularly useful for the treatment or prophylaxis of CMV infections. The use of the compounds of the invention in the preparation of a medicament for the treatment of viral infections is also described. Other viral conditions that can be treated according to the invention have been described in the introduction herein. In a still further aspect of the present invention, there are provided: a) a method for the treatment or prophylaxis of a hepadnaviral infection such as hepatitis B or herpes viral infection, such as CMV, which comprises treating the patient with an amount Therapeutically effective of a compound according to the invention. b) The use of a compound according to the invention in the manufacture of a medicament for the treatment or prophylaxis of any of the aforementioned infections or conditions. "A pharmaceutically acceptable derivative" means any salt, ester, or salt of said ester pharmaceutically or pharmacologically acceptable of a compound according to the invention, or any compound that, when administered to the recipient, is capable of providing (directly or indirectly) a compound according to the invention, or an antivirally active metabolite or residue thereof.

The term "heterocyclic ring" means a saturated, unsaturated, or partially saturated ring containing one or more heteroatoms independently selected from nitrogen, oxygen, and sulfur. Examples of these groups include acetidinyl, pyrrolidinyl, and piperidinyl. Preferred esters of the compounds of the invention include carboxylic acid esters, wherein the non-carbonyl moiety of the ester grouping is selected from straight or branched chain alkyl, e.g., normal propyl, butyl tertiary, normal butyl, alkoxylalkyl (e.g., methoxymethyl), aralkyl (e.g., benzyl), aryloxyalkyl (e.g., phenoxymethyl), aryl (e.g., phenyl optionally substituted by halogen, 1 to 4 carbon atoms, or alkoxy of 1 to 4 carbon atoms, or amino); sulfonate esters such as alkyl- or aralkyl sulfonyl (e.g., methanesulfonyl); amino acid esters (e.g., L-valyl or L-isoleucyl); and mono-, di-, or tri-phosphate esters. The phosphate esters can be further esterified, e.g., with an alcohol of 1 to 20 carbon atoms, or a reactive derivative thereof, or with a 2,3-diacyl (of 6 to 24 carbon atoms) glycerol. With respect to the above-described esters, unless otherwise specified, any alkyl moiety present conveniently contains from 1 to 18 carbon atoms, particularly from 3 to 6 carbon atoms, such as pentanoate. Any aryl fraction present in these esters conveniently comprises a phenyl group. Any reference to any of the above compounds also includes a reference to a pharmaceutically acceptable salt thereof. Physiologically acceptable salts include salts of organic carboxylic acids, such as acetic, lactic, tartaric, malic, and cetionic, lactobionic, p-aminobenzoic, and succinic acids; organic sulfonic acids such as methanesulfonic, ethanesulfonic, benzenesulfonic, and p-toluenesulfonic acids, and inorganic acids such as hydrochloric, sulfuric, phosphoric, and sulfamic acids. The above compounds according to the invention, and their pharmaceutically acceptable derivatives, can be used in combination with other therapeutic agents for the treatment of the above infections or conditions. Additional examples of these therapeutic agents include agents that are effective for the treatment of viral infections, or associated conditions, such as acyclic nucleosides (e.g., acyclovir), immunomodulatory agents such as thymosin, ribonucleotide reductase inhibitors such as cyclosporine. -acetylpyridin-5- [(2-chloroanilino) thiocarbonyl] thiocarbonohydrazone, interferons such as a-interferon, l-jS-arabinofuranosyl-5- (1-propynyl) uracil, 3 '-azido-3' -deoxythymidine, ribavirin, and phosphonoformic acid. The component compounds of this combination therapy can be administered simultaneously, either in separate or combined formulations, or at different times, for example, in sequence, such that a combined effect is achieved. The compounds according to the invention, also referred to herein as the active ingredient, can be administered for therapy by any suitable route, including oral, rectal, nasal, local (including transdermal, buccal, and sublingual), vaginal and parenteral. (including subcutaneous, intramuscular, intravenous, and intradermal). It will be appreciated that the preferred route will vary with the condition and age of the recipient, the nature of the infection, and the active ingredient selected. In general, a suitable dose for each of the aforementioned conditions will be in the range of 0.01 to 250 milligrams per kilogram of body weight of the recipient (eg, a human being) per day, preferably at the scales of 0.1 to 100 milligrams per kilogram of body weight per day, and more preferably on the scale of 1.0 to 20 milligrams per kilogram of body weight per day. (Unless otherwise indicated, all weights of the active ingredient are calculated as the parent compound of the formula (I), for the salts or esters thereof, the weights would increase in a proportional manner). The desired dose of preference is presented as two, three, four, five, six, or more sub-doses administered at appropriate intervals throughout the day. These sub-doses can be administered in unit dosage forms, for example, containing from 10 to 1,000 milligrams, preferably from 20 to 500 milligrams, and more preferably from 100 to 400 milligrams of active ingredient per unit dosage form. Ideally, the active ingredient should be administered to achieve peak plasma concentrations of the active compound from about 0.025 to about 100 μM, preferably from about 0.1 to 70 μM, more preferably from about 0.25 to 50 μM. This can be achieved, for example, by intravenous injection of a solution of 0.1 to 5 percent of the active ingredient, optionally in serum, or it can be administered orally as a bolus containing from about 0.1 to about 250 milligrams per kilogram of the ingredient. active. Desirable blood levels can be maintained by continuous infusion to provide from about 0.01 to about 5.0 milligrams / kilogram / hour, or by intermittent infusions containing from about 0.4 to about 15 milligrams / kilogram of the active ingredient. Although it is possible for the active ingredient to be administered alone, it is preferable to present it as a pharmaceutical formulation. The formulations of the present invention comprise at least one active ingredient, as defined above, together with one or more acceptable vehicles thereof, and optionally other therapeutic agents. Each vehicle must be "acceptable" in the sense of being compatible with the other ingredients of the formulation, and not harmful to the patient. The formulations include those suitable for oral, rectal, nasal, local (including transdermal, buccal, and sublingual), vaginal or parenteral (including subcutaneous, intramuscular, intravenous, and intradermal) administration. The formulations may conveniently be presented in a unit dosage form, and may be prepared by any methods well known in the art of pharmacy. These methods include the step of bringing the active ingredient into association with the vehicle that constitutes one or more accessory ingredients. In general, the formulations are prepared by uniformly and intimately bringing into association the active ingredient with the liquid carriers, or the finely divided solid carriers, or both, and then, if necessary, configuring the product. Compositions suitable for transdermal administration may be presented as separate patches adapted to remain in intimate contact with the hepidermis of the recipient for a prolonged period of time. These patches suitably contain the active compound 1) in an optionally regulated aqueous solution, or 2) dissolved and / or dispersed in an adhesive, or 3) dispersed in a polymer. A suitable concentration of the active compound is from about 1 percent to 25 percent, preferably from about 3 percent to 15 percent. As a particular possibility, the active compound can be applied from the patch by electrotransport or iontophoresis, as generally described in Pharmaceutical Research, 3 (6), 318 (1986). Formulations of the present invention suitable for oral administration may be presented as separate units, such as capsules, dragees, or tablets, each containing a predetermined amount of the active ingredient.; as a powder or granules; as a solution or suspension in an aqueous or non-aqueous liquid; or as an oil-in-water liquid emulsion or a water-in-oil liquid emulsion. The active ingredient can also be presented as a bolus, electuary, or paste. A tablet can be made by compression or molding, optionally with one or more auxiliary ingredients. Compressed tablets can be prepared by compressing in a suitable machine the active ingredient in a free-flowing form, such as a powder or granules, optionally mixed with a binder (e.g., povidone, gelatin, hydroxypropylmethylcellulose), lubricant, inert diluent, preservative, disintegrant (eg, sodium starch glycolate, crosslinked povidone, crosslinked sodium carboxymethyl cellulose), or with a surface active or dispersing agent. The molded tablets can be made by molding in a suitable machine, a mixture of the powdered compound moistened with an inert liquid diluent. The tablets may optionally be coated or scored, and may be formulated to provide a slow or controlled release of the active ingredient thereof, using, for example, hydroxypropylmethylcellulose in different proportions, to provide the desired release profile. The tablets may optionally be provided with an enteric coating, to provide release in portions of the intestine other than the stomach. Formulations suitable for local administration in the mouth include dragees, which comprise the active ingredient in a flavored base, usually sucrose and acacia or tragacanth; pills comprising the active ingredient in an inert base, such as gelatin and glycerin, or sucrose and acacia; and mouth rinses comprising the active ingredient in a suitable liquid vehicle.

Formulations for rectal administration may be presented as a suppository with a suitable base comprising, for example, cocoa butter or a salicylate. Formulations suitable for vaginal administration may be presented as pessaries, buffers, creams, gels, pastes, foams, or spray formulations containing, in addition to the active ingredient, vehicles that are known in the art as appropriate. Formulations suitable for parenteral administration include sterile aqueous and non-aqueous isotonic injection solutions, which may contain anti-oxidants, pH regulators, bacteriostats, and solutes which render the formulation isotonic with the blood of the intended recipient; and aqueous and non-aqueous sterile suspensions, which may include suspending agents and thickening agents. The formulations can be presented in sealed single-dose or multi-dose containers, for example, ampoules and flasks, and can be stored in a freeze-dried (lyophilized) condition, requiring only the addition of the sterile liquid carrier, for example , water for injections, immediately before use. Extemporaneous injection solutions and suspensions can be prepared from sterile powders, granules, and tablets of the kind described above. Preferred unit dosage formulations are those containing a daily dose or unit, a daily sub-dose as mentioned hereinabove, or an appropriate fraction thereof, of an active ingredient. It should be understood that, in addition to the ingredients particularly mentioned above, the formulations of this invention may include other agents conventional in the art, considering the type of formulation in question, for example, those suitable for oral administration may include other agents such as Sweeteners, thickeners, and flavoring agents. The present invention also includes the following process, illustrated schematically, for the preparation of the compounds of this invention: Base, v.gr. K2C0j or triethylamine Solvent such as (Where is a tertiary butanol group removable dioxane, dimethylformamide for example, halogen, in particular chlorine) 1) RYO2H, heat (for RI * = H, alkyl, perfluoroalkyl) Oi). - (i) 2) N-halosuccinimide (for R4 = halogen) 3) Cyanogen bromide (for R ** = NH2) Accordingly, in accordance with a further feature of the present invention, we provide a process for the preparation of compounds of formulas (I) and (1-1), alone or in combination with their mirror image enantiomers, and their derivatives pharmaceutically acceptable, which comprises (A) reacting: or the mirror image enantiomer thereof, with a) either a compound of the formula R4C02H, wherein R4 is H, alkyl of 1 to 4 carbon atoms, or perfluoroalkyl of 1 to 4 carbon atoms, preferably a an elevated temperature, or a compound of the formula R 4 C (0R) 3, wherein R 4 is H, alkyl of 1 to 4 carbon atoms, or perfluoroalkyl of 1 to 4 carbon atoms, and R is alkyl of 1 to 4 atoms carbon, preferably at room temperature and in an acid medium, to form a compound of the formula (I) or (1-1), wherein R4 is H, or b) cyanogen bromide, to form a compound of the formula (I) or (1-1), wherein R 4 is NH 2; or (B) a) converting a compound of the formula (I) or (I-1), wherein R4 is hydrogen, into an additional compound of the formula (I) or (1-1), wherein R * is a releasable group, e.g., by treating it with an N- (C1, Br, or I) succinimide, to form a compound wherein R4 is Cl, or Br, and b) converting a compound of the formula (I) or (I-1), wherein R4 is Cl or Br, in an additional compound of the formula (I) or (1-1), wherein R4 is an amino or substituted amino-NR8R9 group as defined above, by its treatment with an alkylamine of 1 to 4 carbon atoms or dialkylamine of 1 to 4 carbon atoms, or R8R9NH, wherein R8 and R9 are defined as above, or (C) reacting a compound of the formula: (wherein R 4, R 5, R 6, and R 7 are as defined above herein), or a functional equivalent thereof, with a compound of the formula: wherein R1, R2, and R3 are as defined above, and L is a releasable group, for example, an organosulfonyloxy group (e.g., p-toluenesulfonyloxy or methanesulfonyloxy), halogen, or a triflate group (0S02CF3), e.g., in the presence of a base, such as sodium carbonate or sodium hydride, in a solvent such as dimethylformamide, conveniently at an elevated temperature, e.g., from 80 ° C to 100 ° C, for forming a compound of the formula (I) or (1-1), wherein R4 is hydrogen, halogen, or NR8R9; and optionally converting a compound of the formula (I) or (1-1) to a pharmaceutically acceptable derivative thereof. Alternatively, in the process (C) above, the compound of the formula (IV) can be replaced with a compound wherein the L and R3 groups are replaced with a cyclic sulfate group. All the structures shown above are intended to represent the illustrated enantiomers, as well as their mirror image isomers, as well as mixtures thereof. Accordingly, the present invention is intended to encompass both the racemates and the pure enantiomers, substantially free of their mirror image isomers. A compound of formula (I) or (1-1) can be converted to a pharmaceutically acceptable ester by its reaction with an appropriate esterifying agent, e.g., an acid halide or anhydride. The compound of the formula (I) or (1-1), including the esters thereof, can be converted to pharmaceutically acceptable salts thereof in a conventional manner, e.g., by treatment with an appropriate acid. An ester or a salt of an ester of the formula (I) or (I-1) can be converted into the parent compound, e.g., by hydrolysis. The following Examples are intended for illustration only, and are not intended to limit the scope of the invention in any way. The term "active ingredient", as used in the examples, means a compound of the formula (I) or (I-1), or a pharmaceutically acceptable derivative thereof. Example A: Tablet Formulations The following formulations A and B were prepared by wet granulation of the ingredients with a povidone solution, followed by addition of magnesium stearate, and compression. Formulation A ms / tablet a / tablet (a) 250 250 active ingredient (b) lactose B.P. 210 26 (c) Povidone B.P. 15 9 (d) Starch glycolate of so > ddiioo 20 12 (e) magnesium stearate 5 3 500 300 Formulation B ma / tablet ma / tablet (a) 250 250 active ingredient (b) lactose 150 - (c) Avicel PH 101 60 26 (d) Povidone B.P. 15 9 (e) Sodium starch glycolate 20 12 (f) Magnesium stearate 5 3 500 300 Formulation B ma / tablet Active ingredient 100 Lactose 200 Starch 50 Povidone 5 Magnesium stearate 4 359 The following formulations D and E were prepared by direct compression of the mixed ingredients. The lactose used in formulation E was of the direct compression type (Dairy Crest - "Zeparox"). Formulation D mq / tablet Active ingredient 250 Pregelatinized starch NF15 150 400 Formulation E ma / tablet Active ingredient 250 Lactose 150 Avicel 100 500 Formulation F (Controlled Release Formulation) The formulation was prepared by wet granulation of the ingredients (below), with a povidone solution, followed by the addition of magnesium stearate, and compression. ma / tablet (a) active ingredient 500 (b) hydroxypropylmethylcellulose 112 (Methocel K4M Premium) (c) Lactose B.P. 53 (d) Povidone B.P.C. 28 (e) Magnesium stearate 7 700 Example B; Capsule Formulation Formulation A A capsule formulation was prepared by mixing the ingredients of Formulation D of Example 1 above, and filling into a two part hard gelatin capsule. Formulation B (infra) was prepared in a similar manner. Formulation B ma / capsule (a) Active ingredient 250 (b) Lactose B.P. 143 (c) Sodium starch glycolate 25 (d) Magnesium stearate 2 420 Formulation C ma / capsule * (a) Active ingredient 250 (b) Macrogol 4000 BP 350 600 Capsules were prepared by melting the macrogol 4000 BP, dispersing the active ingredient in the melt, and filling the melt in a two part hard gelatin capsule. Formulation D mq / capsule Active ingredient 250 Lecithin 100 Arachis oil 100 450 Capsules were prepared by dispersing the active ingredient in the lecithin and arachis oil, and filling the dispersion in soft elastic gelatin capsules. Formulation E (Controlled Release Capsule) The following controlled release capsule formulation was prepared by extruding ingredients a, b, and e, using an extruder, followed by spheronization of the extrudate, and drying. The dried granules were then coated with a release control membrane (d), and filled into a two-piece hard gelatin capsule. a / capsule (a) Active ingredient 250 (b) Microcrystalline cellulose 125 (c) Lactose BP 125 (d) Ethylcellulose 13 513 Example C: Injectable Formulation Formulation A Active ingredient 0.200 grams Hydrochloric acid solution, 0. IM c.s. to a pH of 4.0 to 7.0 Sodium hydroxide solution, 0. IM c.s. to a pH of 4.0 to 7.0 Sterile water q.s. up to 10 ml The active ingredient was dissolved in most of the water (35 ° C to 40 ° C), and the pH was adjusted between 4.0 and 7.0 with hydrochloric acid or sodium hydroxide, as appropriate. Then the batch was filled up to the volume with water, and filtered through a sterile micropore filter, towards an amber glass bottle of; 10 milliliters sterile (type 1), and sealed with sterile closures and seals.

Formulation B Active ingredient 0.125 grams Phosphate regulator with a pH of 7, sterile, free of pyrogen. c.s. to 25 ml Example D; Intramuscular injection Active ingredient 0.20 grams Benzyl alcohol 0.10 grams Glycofurol 1.45 grams Water for injection q.s. up to 3.00 ml The active ingredient was dissolved in the glycofurol. Then the benzyl alcohol was added and dissolved, and water was added to 3 milliliters. The mixture was then filtered through a sterile micropore filter, and sealed in sterile 3 milliliter amber glass jars (type 1).

Example E; Syrup Active ingredient 0.2500 grams Sorbitol solution 1.5000 grams Glycerol 2.0000 grams Sodium benzoate 0.0050 grams Flavor, peach, 17.42.3169 0.0125 milliliters Purified water q.s. Up to 5.0000 ml The active ingredient was dissolved in a mixture of glycerol and most of the purified water. Then an aqueous solution of sodium benzoate was added to the solution, followed by the addition of the sorbitol solution, and finally the flavoring. The volume was filled with purified water, and mixed well. Example F: Suppository ma / suppository Active ingredient (63 m) * 250 Hard fat, BP (Witepsol H15 - Dynamit Nobel] 1770 2020 * The active ingredient was used as a powder, where at least 90 percent of the particles were of a diameter of 63 microns or less One-fifth of the Witepsol H15 was melted in a steam jacket at a maximum of 45 ° C. The active ingredient was sliced through a 200 micron sieve and added to the base melted by mixing, using a silverson adapted with a cutting head, until a smooth dispersion was achieved.Maintaining the mixture at 45 ° C, the remaining Witepsol H15 was added to the suspension, and stirred to ensure a homogenous mixture. the suspension was passed through a stainless steel mesh of 250 microns, and with continuous agitation, it was allowed to cool to 40 ° C. At a temperature of 38 ° C to 40 ° C, 2.02 grams of the mixture were filled into molds. of 2 milliliters of suitable plastic. suppositories were allowed to cool to room temperature. Example G; Pesarios ma / pesario Active ingredient (63 micras) 250 Dextrose anhydrate 380 Potato starch 363 Magnesium stearate 7 1000 The above ingredients were mixed directly, and pessaries were prepared by direct compression of the resulting mixture. Antiviral Test 1. Anti-CMVH Human cytomegalovirus (HCMV) is tested in monolayers of MRC5 (human embryonic lung) cells in multi-well trays. The activity of the compounds is determined in the plaque reduction assay, wherein a cell monolayer is infected with a suspension of HCMV. A range of concentrations of the compound to be tested (of a known molarity) is then incorporated into the superimposition of carboxymethylcellulose. The plate numbers of each concentration are expressed as a percentage of the control, and a response curve is drawn to the dose. From this curve, an inhibitory concentration of 50 percent (IC50) is estimated. • Anti-CMVH Activity Compound Cl50 (um) Example 4 1.9 2. Anti-HBV a. Panorama; The anti-HBV activity of the compounds of the formulas (I) and (1-1) was determined with a high capacity assay to evaluate the efficacy. Supernatants of growing HBV producing cells (HepG22.2.15 cell line, P5A) are applied in 96-well dishes, the microtiter dish wells which have been coated with a monoclonal antibody specific for the HBV surface antigen (HBsAG). The virus particles present in the supernatants bind to the antibody, and remain immobilized, while other debris is removed by washing. These virus particles are then denatured to release the HBV DNA strands, which are subsequently amplified by the polymerase chain reaction, and detected by a hybrid capture colorimetric assay. Quantification is achieved by adjusting a standard curve to dilutions of a cell supernatant with a known HBV gDNA content. By comparing the HBV gDNA levels of the supernatants of the untreated control cells, with the supernatants containing a compound of the formula (I) or (I-1), a measure of effectiveness against HBV is obtained. b. Immunoaffinity Capture of HBV: VHB producing cells, 2500 cells / well, were seeded in 96-well culture dishes, in RPMI / 10 percent fetal bovine serum / 2mM glutamine (RPMI / 10/2 :). The media was filled on days 1, 3, 5, and 7 with dilutions of a compound of the formula (I) or (1-1) in RPMI / 10/2, to a final volume of 150 microliters. 50 microliters of anti-HBsAG mouse monoclonal antibody (10 micrograms / milliliter in PBS) was added to each well of a round bottom microtiter dish. After incubation overnight at 4 ° C, the solutions were aspirated and replaced with 100 microliters of 0.1% bovine serum albumin in PBS. The samples were incubated for 2 hours at 37 ° C, and washed three times with PBS / 0/01% Tween-20 (PBS / T) using a Nunc Washer. Then 10 microliters of 0.035% Tween 20 in PBS was added to all the cavities by means of Pro-Pette. The cell supernatants (25 microliters) containing the extracellular virion DNA were transferred to the cavities by Pro / Pette; The final Tween concentration is 0.01 percent. Dilutions of 25 microliter standard VHB medium in RPMI / 10/2 were added to two rows of wells to serve as a standard internal curve for quantification, and dishes were sealed and incubated at 4 ° C overnight. The samples were washed five times with PBS / T and twice with PBS, aspirating the last wash. Next, 25 microliters of 0.09N NaOH / 0.040% NP40 was added to each cavity by Pro / Pette, and the sample cavities were sealed and incubated at 37 ° C for 60 minutes. The samples were then neutralized with 25 microliters of 0.09 N HCl / 100 mM tris (pH 8.3). c. Polymerase chain reaction (PCR); The polymerase chain reaction (Saiki, R.K. et al., Science, 239 (4839) 487-91 (1988)) was carried out on 5 microliter samples, using a Perkin Elmer polymerase chain reaction kit. The polymerase chain reaction is performed in "MicroAmp tubes" in a final volume of 25 microliters. Primers were selected from the conserved regions of the HBV genome, determined by alignment of the different sequences. A primer is biotinylated at the primer end 5 to facilitate detection of the hybrid capture of the polymerase chain reaction products. All primers were purchased from Sybthecell Corp., Rockville, MD, 20850. d. Detection of Hybrid Capture of Polymerase Chain Reaction Products; The products of the polymerase chain reaction were detected with oligonucleotide probes labeled with horseradish peroxidase (Synthecell Corp., Rockville, MD 20850), which hybridize in biotinylated chains of denatured products of the polymerase chain reaction directly into cavities of microtiter plates coated with streptavidin, essentially using the method of Holodiniy, M. et al., BioTechniques, 12 ( 1) 37-39 (1992). The modifications included the use of polymerase chain reaction volumes of 25 microns, and denaturation with sodium hydroxide instead of heat. The simultaneous binding of the biotin fraction to the streptavidin fixed to the dish during hybridization serves to "capture" the hybrids. The unfixed labeled probes were washed before the co-calorimetric determination of the fixed strong rooted peroxidase (hybridized). Amounts of HBV DNA present in the original samples were calculated by comparison with the standards. These values were then compared with those from untreated cell cultures, to determine the degree of anti-HBV activity. The IC50 '(the average inhibitory concentration) is the amount of compound that produces a 50 percent decrease in HBV DNA. The approximate IC 50 is tabulated for the compounds of Examples 4, 13, and 69. Anti-HCMV Activity Compound CI »(μM) Example 4 0.74, 2.5 Example 32 1.3, 0.79 Example 33 0.44, 0.50 Example 40 2.0, 1.4 Example 41 0.4, 0.40 ganciclovir (control) 1.1 (average of 10 values) Example 1 Diacetate (+) (-1R * .2S * .3S * .5S *) -3- (Acetoxy ethyl) -5- (4,5-dichloro-2-nitroanilino) -l., 2-cyclopentanediyl N- [2,3-dihydroxy-4- (hydroxymethyl) -1-cyclopent y 1] carbamate from (±) - (IR *, 2S *, 3S *, 5S *) -terbutyl (6.27 grams, 25.1 mmol) and IN hydrochloric acid (50 milliliters). The resulting clear solution was concentrated in vacuo and dried by evaporation of methanol and ethanol, to give the hydrochloride of (+) - (IS *, 2R *, 3R *, 5R *) -3-amino-5- (hydroxymethyl) -1,2-cyclopentanediol as a solid foam (4.73 grams). This solid foam was vigorously refluxed with triethylamine (7.5 grams, 75 millimoles), 1, 2, 4-trichloro-5-nitrobenzene (5.84 grams, 25.0 millimoles at 97 percent, Aldrich), and 2-methoxyethanol (75 milliliters) ) for 24 hours. The resulting black mixture was evaporated to dryness, and the residue was chromatographed on silica gel, and the product was leached with methanol: chloroform / 1: 10, as a dark orange crystal (6.9 grams). Crystallization from ethanol-water gave an orange powder (3.00 grams), which was stirred in acetic anhydride (3.0 milliliters) -pyridine (20 milliliters), at room temperature overnight. Evaporation of the volatiles, followed by crystallization from ethyl acetate-hexanes, gave the title compound as orange needles (2.82 grams, 24 percent), m.p. 153-156 ° C; 1 H-NMR (DMS0-d6) d: 8.25 and 7.51 (both s, 1 each, C6H2), 8.07 (d, J = 7.8 Hz, 1, NH), 5.23 and 5.09 (both, 2, 2 CHO), 4.3 (m, 1, CHN), 4.2-4.0 (m, 2, CH20), 2.5-2.35 (m, 2, 2CH), 2.04, 2.03, 2.02 (all s, 9, 3CH3CO), 1.5-1.4 (m , 1, CH). Analysis calculated for C 15 H 20 N 2 O 5 Cl 2: C, 46.67; H, 4.35; N, 6.05; Cl, 15.31. Found: C, 46.66; H, 4.37; N, 6.02; Cl, 15.38. Example 2 Diacetate (+) - (lR * g.2S *, 3S *, 5S ») - 3- (acetoxymethyl) -5- (5,6-dichloro-lH-benzimidazol-1-yl) -1.2 -cyclopentanediyl) (+) - (IR *, 2S *, 3S *, 5S *) -3- (acetoxymethyl) -5- (4,5-dichloro-2-nitroanilino) -1,2-cyclopentanediyl diacetate were stirred. (2.75 grams, 5.93 millimoles) and Raney nickel (slurry, Aldrich, 300 milligrams wet) in isopropanol (250 milliliters) under hydrogen (2.8 kg / cm2) on a Parr shaker for 2.25 hours. The catalyst was filtered with celite, and the filtrate was acidified with 98 percent formic acid (5 milliliters), and concentrated to an orange oil. The oil was diluted with additional 98 percent formic acid (45 milliliters), and the resulting orange solution was refluxed for 40 minutes. The volatiles were removed, and the remaining dark oil was dissolved in chloroform (100 milliliters). The chloroform solution was washed with saturated aqueous sodium bicarbonate (3 x 10 milliliters), dried (sodium sulfate), and evaporated to a foam, which was chromatographed on silica gel. The title compound was leached with methanol: chloroform / 3: 97 as a white foam from ethyl acetate (2.26 grams, 86 percent); ^ -NMR (DMSO-d6) 5: 8.57, 8.17, 7.97 (all s, 1 each, 3 benzimidazole CH), 5.6 (m, 1, CHO), 5.3-5.1 (m, 2, CHO and CHN), 4.35-4.15 (m, 2, CH20), 2.6-2.4 (m, overlapping solvent, 2 CH), 2.10, 2.06, 1.92 (all s) removed by 2.0 (, total 10, 3CH3CO and CH). Analysis calculated for C19H2ON206C12: C, 51.49; H, 4.55; N, 6.32; Cl, 16.00. Found: C, 51.39; H, 4.58; N, 6.22; Cl, 16.07. Example 3 Diacetate of (+) - (1R ».2S *, 3S * .5S *) -3- (acetoxymethyl) -5- (2-bromo-5,6-dichloro-lH-benzimidazole-i-yl) -1, 2-cyclopentanediyl) Diacetate of (+) - (IR *, 2S *, 3S *, 5S *) -3- (acetoxymethyl) -5- (5,6-dichloro-lH-benzimidazol-1-yl) - was heated 1,2-cyclopentanediyl) (1.32 grams, 2.98 mmol) in dry N, N-dimethylformamide (6 milliliters) at 60 ° C. Portions (approximately 1 millimole each) of N-bromosuccinimide (1.59 grams) were added, 8.93 millimoles) for 5 hours. The heating was continued for an additional 4 hours. The volatiles were removed in vacuo, and the residue was chromatographed on silica gel. The title compound was leached with 1: 1 hexane-ethyl acetate as a tan powder (1.1 grams, 69 percent), 1 H-NMR identical to that of the recrystallized sample. This sample was recrystallized from ethanol-water to obtain a white powder, m.p. 156-159 ° C; XH-NMR (DMSO-d6) 5: 8.34, 7.97 (both s, 1 each, 2 benzimidazole CH), 5.6 (m, 1, OCH), 5.3 (m, 1, OCH), 5.2-5.0 (, 1 , NCH), 4.4-4.2 (m, 2, OCH2), 2.7-2.5 (m, 1, CH), 2.4-2.0 (m) overlapped 2.1 and 2.07 (both s, total 8, CH2 and 2CH3CO), 1.92 ( s, 3, CH3C0); mass spectrum (Cl): 527 (6.6), 525 (45), 523 (100), 521 (65, M + 1), 257 (48, M-B). Analysis calculated for C19H19N206 BrCl2: C, 43.71; H, 3.67; N, 5.37; total halogen as Br, 45.91. Found: C, 43.64; H, 3.63; N, 5.30; total halogen as Br, 45.77. Example 4 (+) - (1R *, 2S * .3S * .5S *) -5- (2-bromo-Sg, 6-dichloro-lH-benzimidazol-1-yl) -3- (hydroxymethyl) -l. 2-cyclopentanediol (+) - (IR *, 2S *, 3S *, 5S *) -3- (acetoxymethyl) -5- (2-bromo-5,6-dichloro-1H-benzimidazole-1-diacetate) was added. il) -1,2-cyclopentanediyl (600 milligrams, 1.15 millimoles) to a stirred mixture of sodium carbonate (122 milligrams) in water (2 milliliters) -ethanol (10 milliliters) -methanol (10 milliliters). After 2.5 hours at room temperature, the pH was adjusted to 7 with glacial acetic acid. The volatiles were removed in vacuo, and the residue was triturated with water (5 milliliters), and filtered to give a white solid. Recrystallization of the solid from 1: 1 ethanol-methanol gave the title compound as a white powder (282 milligrams, 62 percent), m.p. 208-211 ° C; ^ -H-NMR (DMSO-d6) 5: 8.23 (s, 1, benzimidazole H7), 7.95 (s, benzimidazole H4), 5.13 (t, J = 4.1 Hz, 1, CH2OH), 5.03 (d, J = 6.2 Hz, 1, OH), 5.0-4.85 (, 1, H5), 4.71 (d, J = 3.5 Hz, 1, OH), 4.55-4.45 (m, 1, Hl), 3.85-3.80 (, 1, H2), 3.7-3.6 and 3.55-3.45 (both m, 1 each, OCH2), 2.2-1.95 (m, 3, H3, and 2H4); mass spectrum (Cl): 395 (M + l). Analysis calculated for C 13 H 13 N 203 Cl 2 Br: C, 39.43; H, 3.31; N, 7.07; total halogen as Br, 60.52. Found: C, 39.50; H, 3.33; N, 7.02; total halogen as Br, 60.61. Example 5 Benzoate of (la.3ß.4ß) - (3,4-dihydroxy-1-cyclopentyl) methyl To a stirred and cooled (0 ° C) solution of 4-hydroxymethylcyclopentene (J.-P. Depres and AE Green , J. Ora, Chem. 1984. 49, 928-931, and references therein) (37.0 grams, 276 millimoles) in pyridine (450 milliliters), was added benzoyl chloride (32.1 milliliters, 276 millimoles) for 30 minutes. minutes The resulting mixture was stirred at room temperature for 1.25 hours. Water (50 milliliters) was added, and the volatiles were removed in vacuo. The residual oil was dissolved in chloroform, and the solution was extracted with water, and then dried over sodium sulfate. Evaporation of the solvent gave (3-cyclopenten-1-yl) methyl benzoate as a yellow oil (53.94 grams, 91 percent), pure enough to be used; XH-NMR (DMS0-d6) < S: 7.98, 7.67, 7.56 (m, 5, C6H5), 5.72 (s, 2, CH = CH), 4.19 (m, 2, OCH2), 2.71 (m, 1, CH), 2.56-2.77 (m, overlapping solvent, 2CH), 2.21-2.14 (m, 2, 2CH). Benzoate (3-cyclopenten-1-yl) methyl (37.6 grams, 0.161 mole) in acetone (200 milliliters) was added dropwise over 2 hours to a stirred solution of N-methylmorpholine N-oxide (33.1 grams, 70%). percent in water, 0.169 moles), osmium tetroxide (2.5 percent in tertiary butanol, Aldrich, 3.0 milliliters), and acetone 8200 milliliters), at room temperature. Stirring was continued for an additional 16 hours. Chloroform (500 milliliters) and water (150 milliliters) were added. The organic layer was separated, washed with cold IN hydrochloric acid (2 x 150 milliliters), and then with saturated aqueous sodium bicarbonate (100 milliliters), and dried (MgSO4). The volatiles were removed, and the residual solid was crystallized from toluene (200 milliliters), to give the title compound as white crystals (26.9 grams, 73 percent), m.p. 92-94 ° C; 1 H-NMR (DMSO-d 6) S: 7.96, 7.65, 7.56 (, 5, C6H5), 4.38 (d, J = 4.1 HZ, 2, 20H), 4.14 (d, J = 6.6 Hz, 2, CH20), 3.90 (, 2, 2 OCH), 2.58 (m, overlapping solvent, CH), 1.75 (m, 2, 2CH), 1.55 (m, 2, 2CH). Analysis calculated for C13H1604: C, 66.09; H, 6.83. Found: C 66.19; H, 6.86. The concentration of the mother liquors yielded 10.33 grams of a white solid, which contained additional title compound contaminated with (+) - (la, 3ß, 4ß) - (3,4-dihydroxy-1-cyclopentyl) methyl benzoate, in a ratio of approximately 2: 3 by means of - '? - NMR. Example 6 S-benzoate oxide of (3a-a, 5a, 6a-a) - (tetrahydro-4H-cyclopenta-1,3,2-dioxathiol-5-yl) methyl Thionyl chloride (6.04 grams, 50.8 mmol) was added to a benzoate solution of (l, 3a, 4a) - (3,4-dihydroxy-l-cyclopentyl) methyl (10.0 grams, 42.3 mmol) in carbon tetrachloride (150 milliliters). The solution was refluxed for 1.5 hours. The solvent was evaporated to leave the title compound as a thick oil, sufficiently pure to be used (see the following example). This sample was crystallized as a waxy solid from toluene, m.p. 48-57 ° C; 1 H-NMR (DMS0-d 6) 5: 7.96, 7.66, 7.52 (m, 5, C6H5), 5.46 and 5.32 (both m, 1, 2 OCH, due to a mixture of approximately 1: 1 of S-isomeric oxides) , 4.28 (m, 2, 0CH2), 2.90 and 2.43 (both m, 1, CH of two isomeric S-oxides), 2.10 and 1.74 (both, 4, 4CH). Analysis calculated for C13H1405S: C, 55.31; H, 5.00; S, 11.36. Found: C, 55.41; H, 5.04; S, 11.30. Example 7 SS-benzoate dioxide of (3a-a.5a.6a-a) - (tetrahydro-4H-cyclopenta-1, 3.2-dioxathiol-5-yl) methyl S-benzoate oxide of (3a-a) was stirred , 5a, 6a-a) - (tetrahydro-4H-cyclopenta-1, 3,2-dioxathiol-5-yl) ethyl (foregoing example, 42.3 mmol) in carbon tetrachloride (40 milliliters) -acetonitrile (40 milliliters-water (60 milliliters), while adding sodium metaperiodate (8.98 grams, 42.3 milliequivalents) and ruthenium trichloride (44 milligrams, 0.21 milliequivalents) .Additional sodium metaperiodate (179 milligrams) was added after 30 minutes, to finish the reaction, as judged by thin layer chromatography (silica gel, methanol: chloroform / 1: 19, visualized in iodine) After a total of 1.0 hour, methylene chloride (300 milliliters) was added.The organic layer was separated, and The aqueous layer was extracted with additional methylene chloride (300 milliliters), The combined organic layers were washed with aqueous sodium bicarbonate. The mixture was dried (100 milliliters), and then saturated aqueous sodium chloride (100 milliliters), dried (MgSO 4), and concentrated in vacuo to give the title compound as a white powder (12.37 grams, 98 percent), m.p. 114-119 ° C; ^ -H-FtMN (DMSO-d6) d: 8.02, 7.70, 7.55 (all m, 5, C6H5), 5.62 (m, 2, OCH), 4.34 (d, J = 5.8 Hz, 2 0CH2), 2.79- 2.64 (m, 1, CH), 2.32-2.21 and 1.97-1.79 (m, 4, 2 CH2). Analysis calculated for C13H14S06: C, 52.35; H, 4.73; S, 10.75. Found: C, 52.32; H, 4.73; S, 10.69. Example 8 (±) - (lR * .2R * .4S *) - 2- (5,6-dichloro-lH-benzimidazol-1-yl) -4- (hydroxymethyl) cyclopentyl Sodium hydride (416 milligrams, 10.4 milliequivalents as a dispersion in oil at 60 percent) to a solution of 5,6-dichlorobenzimidazole (LB Townsend and GR Revankar, Chem. Rev. 1970, 70, 389, and references thereof (1.50 grams, 8.00 millimoles) in dry N, N-dimethylformamide (35 milliliters) The mixture was stirred for 45 minutes at 25 ° C. S, S-benzoate dioxide of (3a-a, 5a, 6a-a- (tetrahydro-4H-) was added. cyclopenta-1,3,2-dioxathiol-5-yl) methyl (3.05 grams, 10.2 mmol) (prepared in Examples 7, 8, and 9) in portions over 5 hours.The stirring was continued overnight at room temperature The volatiles were removed in vacuo, and the residual oil was dissolved in 1,4-dioxane (130 milliliters) -water (10 milliliters), at reflux, with 4M sulfuric acid (2.3 milliliters) .After 10 minutes at reflux , the solution was based on h 5N sodium hydroxide, heated for an additional 1 hour at 50 ° C, and then neutralized with additional acid. Evaporation of the volatiles in vacuo gave residual solids which were extracted with chloroform to remove the unreacted 5,6-dichlorobenzimidazole, and then crystallized from ethanol-water to give the title compound as a white powder (2.09 grams, 87 percent). Recrystallization of this sample from ethanol-water gave the title compound as white granules, m.p. 244-245 ° C; 1 H-NMR (DMS0-d 6) d: 8.47, 8.05, 7.93 (all s, 3, aryl CH), 5.19 (d, J = 5.3 Hz, 1, CHOH), 4.71 (T, J = 5.3 Hz, 1, CH2OH), 4.6-4.5 (m, 1, NCH), 4.37-4.25 (m, 1, OCH), 3.41 (m, 2 OCH2), 2.4-2.2 and 1.95-1.62 (m, 5, 5CH). Analysis calculated for C13H14N202C12 »0.02 C2H5OH: C, 51.85; H, 4.71; N, 9.27; Cl, 23.47. Found: C, 51.87; H, 4.74; N, 9.28; Cl, 23.60. Example 9 Acetate of (±) - (lR * .2R *, 4S *) -4- (acetoxymethyl) -2- (5,6-dichloro-lH-benzimidazol-1-yl) cyclopentyl It was dissolved (+) - ( IR *, 2R *, 4S *) -2- (5,6-dichloro-lH-benzimidazol-1-yl) -4- (hydroxymethyl) -cyclopentanol (7.80 grams, 25.8 mmol) in pyridine (50 milliliters) -anhydride acetic acid (50 milliliters), and the solution was stirred overnight. The volatiles were removed in vacuo, and the residual oil was divided between methylene chloride 8150 milliliters) and saturated aqueous sodium bicarbonate (100 milliliters). The organic layer was dried (sodium sulfate) and evaporated to a glass (9.91 grams, 99 percent); - "? - NMR (DMSO-dg) d: 8.58, 8.08, 7.96 (s, 3, aryl CH), 5.39-5.32 (m, 1, OCH), 5.09-5.04 (m, 1, NCH), 4.11 ( d, J = 6.6 Hz, 2, OCH2), 2.59-2.60 (m overlapped solvent, CH), 2.41-2.35 (m, 1, CH), 2.17-1.86 (m overlapped 2.06 and 1.94, both s, total 9, 3CH and 2CH3CO) Analysis calculated for C17H18N2O2Cl2 * 0.1 CH2C12: C, 52.96; H, 4.70; N, 7.26; Cl, 18.55. Found: C, 52.86; H, 4.74; N, 7.25; Cl, 18.50 Example 10 Acetate of (±) - (1R *, 2R *, 4S *) -4- (acetoxymethyl) -2- (2-bromo-5,6-dichloro-lH-benzimidazol-1-yl) -cyclopentyl N-bromosuccinimide was added (4.54 grams, 25.5 mmol) to a solution of (±) - (IR *, 2R *, 4S *) -4- (acetoxymethyl) -2- (5,6-dichloro-lH-benzimidazole-1-yl) acetate ) cyclopentyl (8.95 grams, 23.2 mmol) in dry N, N-dimethylformamide (46 milliliters) The solution was maintained at approximately 70 ° C (oil bath) for 5 hours The volatiles were removed under vacuum, and the syrup was orange residual was passed through chromatography on silica gel The title compound was leached with chloroform as a pale yellow solid (5.14 grams, 48 percent), m.p. 122-125 ° C; 1 H-NMR (DMSO-d6) d: 8.16 (s, 1, benzimidazole H7), 7.95 (s, 1, benzimidazole H4), 5.60-5.55 (m, 1, OCH), 5.12-5.03 (m, 1, NCH) ), 4.15 (d, J = 6.3 Hz, OCH2), 2.66-2.60 (m, 1, CHCH2), 2.29-2.14 (m, 3, CH), 2.06 (s, 3, CH3CO), 1.93 (s overlapped by m, 4, CH 3 CO + CH); mass spectrum (Cl): 469 (5.8), 467 (37.5), 465 (95), 463 (54, M + 1), 199 (100, M-B). Analysis calculated for C 17 H 17 N 2 Cl 2 Br 04: C, 43.99; H, 3.69; N, 6.04; total halogen as Br, 51.65. Found: C, 44.06; H, 3.70; N, 5.97; total halogen as Br, 51.74. Example 11 Analysis of (-) - (ls, 4R) -4-amino-2-cyclopentene-l-methanol? its enantiomer (+) - (IR, 48) -4-amino-2-cyclopentene-1-methanol Samples of the title compounds were characterized by the method of Brückner, H., Wittner, R., and Godel, H., " Automated Enantioseparation of Amino Acids by Derivatization with o-Phthaldialdehyde and N-acylated Cysteines ", J. Chrom., 476 (1989) 73-82. O-phthaldialdehyde and N-acetyl-L-cysteine were used as bypass reagents. The chromatographic separation used a column of 3 micras Optimum II ODS 100 x 4.5 millimeters (III Supplies Co., Meriden, CT), and a leaching gradient of 0.9 milliliters / minute, initially using a 100 percent sodium acetate regulator , 40 mM, pH 6.5, with a linear ramp up to 18 percent acetonitrile for 15 minutes, and a subsequent hold on 18 percent acetonitrile for 15 minutes. The detection was at 338 nanometers. The samples were dissolved in a 0.01 molar borate regulator, pH of 10.4. The identity and purity of the samples were established by a comparison with authentic standards (see European Patent Number EP 434450 (June 26, 1991)). The retention time of the isomer (1R, RS) was approximately 25 minutes. The retention time of the isomer (1R, 4S) was approximately 22 minutes. Example 12 (±) -cis-4-amino-2-cyclopentene-1-methanol A dry, 2-liter, three-necked flask was equipped with a mechanical stirrer, thermometer with gas inlet adapter connected to the nitrogen supply , and sept. The flask was purged with nitrogen, immersed in an ice-acetone bath, and a solution of lithium-aluminum hydride in tetrahydrofuran (1.0 molar, 800 milliliters, 0.80 moles, Aldrich) was added via a cannula. Dry tetrahydrofuran (2 x 15 milliliters) was used to rinse the lithium aluminum hydride solution. When the solution had cooled to 0 ° C, the paste of 4-toluenesulfonate salt of (±) -cis-4-amino-2-cyclopentene-1-carboxylic acid in tetrahydrofuran was cannulated with good agitation, at a high speed such to maintain the temperature at less than 10 ° C, and to moderate the evolution of hydrogen (approximately 1 hour). The flask was rinsed with dry tetrahydrofuran (2 x 15 milliliters), and the septum was replaced by a reflux condenser. The resulting clear light amber solution was heated slowly to a slight reflux during the course of 2 hours, at which point it became cloudy. After refluxing overnight (16 hours), the heating bath was removed, sodium fluoride (136.3 grams, 3.25 moles, reagent grade powder) was added, and the condenser was restored for downward distillation. The mixture was distilled to a thin paste (700 milliliters of distillate was collected), and then cooled in an ice bath. Diethyl ether (dry, 500 milliliters) was added, and the condenser was replaced by an addition funnel containing water (43 milliliters, 2.4 moles). The water was added very slowly (2 hours), taking care to control the rate of evolution of hydrogen, and to maintain the temperature at 10 ± 5 ° C. Meanwhile, water (54 milliliters) was added to the previous recovered distillate, and sufficient additional tetrahydrofuran was added to bring the total volume up to 900 milliliters (H20 at 6 percent). The reaction mixture was filtered by suction, and the cake was washed with tetrahydrofuran (100 milliliters). Part of the 6 percent water-tetrahydrofuran solution (300 milliliters) was used to wash the paste from the cake, which was then returned to the reaction flask. The cake was triturated (25 minutes) in 6 percent water-tetrahydrofuran (400 milliliters), filtered, and washed with 6 percent water-tetrahydrofuran (200 milliliters). The combined filtrates were concentrated to a pale yellow oil under vacuum (44.07 grams, 67.8 percent by high performance liquid chromatography, see Example 3). This oil, which contained the pure title compound, water, and a trace of tosylate salt, darkens rapidly under ambient conditions. It was immediately reacted to form the N-BOC derivative, a stable crystalline solid (see the following example). The filter cake was returned to the flask, and triturated in methanol (800 milliliters) for 48 hours. The resulting paste was filtered under a rubber charm, and the cake was washed with methanol (200 milliliters). The filtrate was concentrated in vacuo to give a yellow solid (56.80 grams, 20.9 percent yield by high performance liquid chromatography).; total yield 88.7 percent). Example 13 (±) -cis-4-amino-2-cyclopenten-l-methanol By the method of Example 12, but on about twice the scale (97.40 grams, 0.8924 moles of (±) -2-azabicyclo [2.2 1] -hept-5-en-3-one), the title compound was obtained as extracts containing the title compound (0.7926 moles, 88.8 percent of theory, allowing aliquots to be removed, determined by the method of Example 11). Example 14 N- (4-hydroxymethyl) -2-cyclopenten-1-yl '| (±) -cis-tertbutyl carbamate The combined tetrahydrofuran extracts from the previous example were concentrated in vacuo to 1031 grams, cooled in an ice water bath, and a mixture of sodium bicarbonate (97.46 grams, 1.16 moles) was added. in water (500 milliliters). This was followed by diterbutyl dicarbonate (204.5 grams, 0.9501 moles). The mixture was stirred at 5 ° C for 2 days. The methanol extracts from the previous example were evaporated to an oily solid (136.64 grams), which was added to the mixture. After warming to room temperature, the organic solvents were evaporated in vacuo, and the resulting paste was extracted with hexanes, 3 portions of methylene chloride, then hexanes again (200 milliliters of each). The organic extracts were evaporated to an oil, which was crystallized from hexanes (approximately 300 milliliters) to give the title compound (154.15 grams, 0.7229 moles). Additional product was obtained by chromatography of the mother liquors (10.5 grams, 0.0491 moles, 86.6 percent of theory from the starting lactam, allowing aliquots to be removed). Example 15 (±) -cis-f4- (4,5-dichloro-2-nitroanilino) -2-cyclopenten-l-i1 * | methanol N- [4- (Hydroxymethyl) -2-cyclopenten-1-yl was stirred ] (+) - cis -tertbutyl carbamate (50.0 grams, 0.230 moles) in 25 percent trifluoroacetic acid in methylene chloride (1.5 liters) at 0 ° C for 1.0 hour. The evaporation of the volatiles left the trifluoroacetic acid salt of the amine described in Example 27 as a dark oil. To this oil was added tertiary butanol (350 milliliters), potassium carbonate (65 grams), and 1, 2, 4-trichloro-5-nitrobenzene (Aldrich, 54.7 grams, 0.230 moles as 97 percent). The resulting mixture was refluxed with vigorous stirring for 3 days. The volatiles were removed in vacuo, and the residue was triturated with methanol. The material soluble in methanol was passed through chromatography on silica gel. The crude product was leached with 2 percent methanol-chloroform, to give an orange solid (38.0 grams). Crystallization from: ethyl acetate-hexanes gave the title compound as orange crystals (34.0 grams, 49 percent), m.p. 96-98 ° C; 1 H-gRMN (DMS0-d6) and mass spectrum (Cl) consistent with the structure and identical to that of the chiral enantiomer samples described in Examples 18 and 26. Analysis calculated for C12H12N2C1203: C, 47.55; H, 3.99; N, 9.24; Cl, 23.39. Found: C, 47.75; H, 4.10; N, 9.20; Cl, 23.52. Continuous leaching of the column gave additional fractions containing the title compound with minor impurities of low Rf. These fractions were combined with the mother liquor of the previous crystallization, and recrystallized from ethyl acetate-hexanes, to give an additional orange solid (16.7 grams), which had an identical 1 H-NMR spectrum, and bore the yield total to 73 percent.

Example 16 Diacetate of (±) - (1R »2S», 3S ».5S *) -3- (acetoxymethyl) -5- (4,5-dichloro-2-nitroanilino) -1,2-cyclopentanediyl and (±) (lR *, 2S ».3S» .5S *) - 3- (acetoxymethyl) -5- (4,5-dichloro-2-nitroanilino) -1,2-cyclopentanediyl To a solution of (+) - cis- [4- (4 , 5-dichloro-2-nitroanilino) -2-cyclopenten-l-yl] methanol (20.0 grams, 66.0 mmol) and N-methylmorpholine N-oxide (Aldrich, 60 percent aqueous solution, 12.0 milliliters, 69 mmol) in acetone 8280 milliliters), osmium tetroxide (2.5 percent in terbutyl alcohol, Aldrich, 1.24 milliliters) was added. After being stirred at room temperature for 18 hours, the volatiles were removed in vacuo, and the residue was stirred with pyridine (200 milliliters) -acetic anhydride (40 milliliters) for an additional 18 hours. The solution was concentrated to a thick red oil, which was divided between saturated aqueous sodium carbonate and chloroform. The chloroform layer was dried (sodium sulfate), and then concentrated to a vacuum oil. A mixture of the isomeric title compounds was leached from a column of silica gel with 2 percent methanol-chloroform, and crystallized from ethyl acetate-hexanes (with a seed of crystals of the isomer (1R * , 2S *) prepared by the method of Example 1), to give diacetate of (+) - (IR *, 2S *, 3S *, 5S *) -3- (acetoxymethyl) -5- (4,5-dichloro- 2-nitroanilino) -1, 2-cyclopentanediyl as orange crystals (17.4 grams, 57 percent), mp 154-156 ° C; - "- H-NMR (DMSO-d6) identical to that of the sample described in Example 1. The continuous crystallization of the content of the mother liquor from ethyl acetate-hexanes, gave diacetate of (+) - (IR * , 2S *, 3S *, 5S *) -3- (acetoxymethyl) -5- (4, 5-dichloro-2-nitroanilino) -1, 2-cyclopentanediyl as orange crystals (8.82 grams, 29 percent), mp 105 -107 ° C; 1H-NMR (DMSO-d6) Analysis calculated for C18H20N2Cl2O8: C, 46.67; H, 4.35; N, 6.05; Cl, 15.31, Found: C, 46.50; H, 4.33; N, 5.96; Cl , 15.23 Example 17 Diacetate of (+) - (1R * .2B * .3S * .5S ») -3- (acetoxymethyl) -5- (2-bromo-5,6-dichloro-lH-benzimidazol-1-yl) -1.2-cyclopentanediyl (+) - (IR *, 2S *, 3S *, 5S *) -3- (acetoxymethyl) -5- (4,5-dichloro-2-nitroanilino) -1, 2-diacetate was stirred. Cyclopentanediyl (5.00 grams, 10.8 mmol) in ammonia / methanol (approximately 2 N, 100 milliliters) at room temperature for 18 hours The evaporation of the volatiles in vacuo left a residual orange solid of (+) - (lR *, 2S *, 3S *, 5S *) - 5- (4,5-dichloro-2-nitroanilino) -3- (hydroxymethyl) -1,2-cyclopentanediol, with an identical Rf on layer chromatography plates thin on silica gel, to that of the chiral sample described in Example 19. This solid was reduced with Raney nickel / hydrogen (3.15 kg / cm2) in isopropanol (200 milliliters). The catalyst was filtered with celite. The washing of the filtrate was evaporated to dryness in vacuo. The residue was refluxed in formic acid (96 percent, 50 milliliters) for 1 hour, as described in Example 2. The remaining oil upon evaporation of the formic acid was dissolved in methanol. The pH was adjusted to 13 with 5N aqueous sodium hydroxide, and the solution was stirred at room temperature for 1 hour to hydrolyze the formates. The pH was adjusted to 7 with IN hydrochloric acid, and the volatiles were removed by evaporation in vacuo. Pyridine (100 milliliters) and acetic anhydride (4 milliliters) were added to the residue, and the mixture was stirred at room temperature overnight. Evaporation of the volatiles in vacuo, followed by chromatography on silica gel with 1 percent methanol-chloroform, gave diacetate of (+) - (1R *, 2S *, 3R *, 5R *) -3 - (acetoxymethyl) ) -5- (5,6-Dichloro-1H-benzimidazol-1-yl) -1,2-cyclopentanediyl as white crystals from ethanol-water (2.6 grams, 53 percent), 1 H-NMR (DMS0-d6) ) consistent with the structure. The diacetate of (+) (IR *, 2S *, 3R *, 5R *) -3- (acetoxymethyl) -5- (5, 6-dichloro-lH-benzimidazol-1-yl) -1,2-cyclopentanediyl (2.5 grams, 5.7 mmol) was dissolved in dry dioxane (15 milliliters), and the solution was refluxed while adding fresh N-bromosuccinimide. recrystallized (2.10 grams, 11.5 millimoles) all at once. After 5 minutes at reflux, the red-brown solution was evaporated in vacuo to a red oil. A chloroform solution of this oil was washed with water and then dried (sodium sulfate). The chloroform solution was concentrated until an oil was obtained, which was chromatographed on silica gel, the fractions containing the product were leached with 2-4% methanol-chloroform. Crystallization from ethyl acetate-hexanes gave a white solid (1.5 grams, 50 percent); • '• H-NMR (DMS0-d6) consistent with the structure of the title compound. This sample was again passed through chromatography on silica gel with leaching by chloroform, to give diacetate of (+) (IR *, 2S *, 3R *, 5R *) -3- (acetoxymethyl) -5- (2- bromo-5,6-dichloro-lH-benzimidazol-1-yl) -1,2-cyclopentanediyl as white crystals, after crystallization from ethyl acetate-hexanes, mp 166-167 ° C; ^ -H-NMR (DMS0-d6) d: 8.14 and 7.96 (both s, 1 each, 2 aromatic CH), 5.6-5.35 (, 3, 2 OCH and NCH), 4.4-4.1 (m, 2, 0CH2 ), 2.8-2.4 (m overlapped solvent, 2 CH), 2.4-2.1 (m overlapped in 2.25, total 4, CH and CH3), 2.04 (s, 3, CH3), 1.37 (s, 1, CH3); mass spectrum (Cl): 525 (53), 523 (100), 521 (54, M + 1). Analysis calculated for C19H19N2BrCl206: C, 43.70; H, 3.67; N, 5.37; total halogen as Cl, 20.37. Found: C, 43.65; H, 3.68; N, 5.35; total halogen as Cl, 20.32. Example 18 (lB, 4R) - [4- (4,5-dichloro-2-nitroanilino) -2-cyclopentenyl-methanol N- [4-hydroxymethyl] -2-cyclopenten-l-yl] carbamate was converted of (-) - (IR, 4S) -terbutyl (15.00 grams, 70.3 mmol) by the method of Example 1, in (lS, 4R) - [4- (4,5-dichloro-2-nitroanilino) -2- cyclopenten-1-yl] methanol, was isolated as a yellow powder after leaching from a column of silica gel with 1: 1 hexanes-chloroform, and resolidification from ethyl acetate-hexanes (9.97 grams, 47 percent), pf 94.5-96.5 ° C; - "- H-NMR (DMSO-d5) 6; 8.24 (s, 1, benzimidazole CH), 8.09 (d, J = 8.1 Hz, 1, NH), 7.51 (s, 1, benzimidazole CH), 5.95 and 5.85 (both m, 2, CH = CH), 4.9-4.7 (m overlapping t at 4.78, J = 5.1 Hz, total 2, CHN and OH), 3.4 (m, 2, CH20), 2.80 (m, 1, CH ), 2.6-2.4 (m overlapped solvent, CH), 1.5-1.4 (m, 1, CH), mass spectrum (Cl): 303 (M + l); [a] 20589 + 199 °, [a] 20578 + 222 or [a] 20546 + 333 ° (c = 0.267, methanol). Analysis calculated for C12H12N2C1203 »0.18 CQH- ^: C, 49. 30; H, 4.59; N, 8.79; Cl, 22.25. Found: C, 49.64; H, 4. 64; N, 8.68; Cl, 22.10. Example 19 (IS, 2R.3R, 5R) -5- (4. S-dichloro-2-nitroanilino) -3- (hydroxymethyl) -1,2-cyclopentanediol and (IR, 2S, 3R, 5R) -5- (4.5 -dichloro-2-nitroanilino) -3- (hydroxymethyl) -1,2-cyclopentanediol To a solution of (ÍS, 4R) - [4- (4,5-dichloro-2-nitroanilino) -2-cyclopenten-l- il] methanol (8.60 grams, 27.6 millimoles) and N-methylmorpholine N-oxide (Aldrich, 60 percent aqueous solution, 5.02 milliliters, 29.0 millimoles) in acetone (90 milliliters), osmium tetroxide (Aldrich, 2.5 percent in terbutyl alcohol, 0.51 milliliters). After stirring at room temperature for 18 hours, an additional 0.25 milliliters of aqueous N-methylmorpholine N-oxide was added, and the solution was stirred for an additional 5 hours. The volatiles were evaporated in vacuo, and the residue was recrystallized twice from 95 percent ethanol, to give (1S, 2R, 3R, 5R) -5- (4,5-dichloro-2-nitroanilino) -3 - (hydroxymethyl) -1, 2-cyclopentanediol as a yellow powder (1.78 grams, 19 percent), mp 197-199 ° C; 1 H-NMR (DMS0-d 6) 5: 8.23 (s, 1, benzimidazole CH), 8.1 (d, J = 7.0 Hz, 1, NH), 7.50 (s, 1, benzimidazole CH), 5.02 (d, J = 4.9 Hz, 1, OH), 4.74 (t, J = 5.1 Hz, 1, CH20H), 4.58 (d, J = 5.1 Hz, OH), 4.0-3.8 (m, 1, NCH), 3.8-3.7 (m , 2, 2 OCH), 3.5-3.4 (m, 2, CH20), 2.45-2.25 (m, 1, CH), 2.1-1.9 (m, 1, CH), 1.4-1.2 (m, 1, CH); mass spectrum (Cl): 337 (M + 1); [a] 20589-106 °, [al20578-118 °, [a] 20546-182 ° (c = 0.273, methanol). Analysis calculated for C12H14N2C1205: C, 42.75; H, 4. 19; N, 8.31; Cl, 21.03. Found: C, 42.84; H, 4.21; N, 8.24; Cl, 21.09.

Chromatography of the mother liquor content on silica gel gave the isomer (IR, 2S) on leaching with 7-8 percent methanol-chloroform; two resolidifications from 90 percent ethanol gave (IR, 2S, 3R, 5R) -5- (4,5-d-chloro-2-nitroani-lino) -3- (hydroxymethyl) -1,2-cyclopentanediol as a yellow powder (1.57 grams, 17 percent), mp 179-181 ° C; XH-NMR (DMSO-d6) S: 8.70 (d, J = 7.1 Hz, NH), 8.22 and 7.32 (both s, 1 each, 2 benzimidazole CH), 5.28 (d, J = 5.6 Hz, 1, OH ), 4.77 (d, J = 3.9 Hz, 1 OH), 4.45 (t, J = 4.9 Hz, 1, CH20H), 4.1-3.9 (m, 3, 2 OCH and NCH), 3.6-3.5 and 3.45-3.35 (both m partially overlapping to H20, 2, CH20), 2.45-2.25 (m, 1, CH), 2.1-3.9 (m, 1, CH), 1.35-1.25 (m, 1, CH); mass spectrum (Cl): 337 (M + 1); [a] 20589-l5.6o, [a] 20578-13.2 °, [a] 20546-4.00 ° (c = 0.250, methanol). Analysis calculated for C12H14N2C1205: C, 42.75; H, 4. 19; N, 8.31; Cl, 21.03. Found: C, 42.87; H, 4.15; N, 8.30; Cl, 21.14. The leaching with 8-10 percent methanol-chloroform gave a white solid (2.9 grams), which showed in - *? gRMN which was a mixture of approximately 1: 1 of the two isomers. Continuous leaching of the column with 10-20 percent methanol-chloroform, gave fractions containing (SS, 2R, 3R, 5R) -5- (4,5-dichloro-2-nitroanilino) -3- (hydroxymethyl) -1,2-cyclopentanediol additional, which was solidified with 90% ethanol percent to a white powder (2.23 grams), bringing the total yield of this isomer up to 43 percent. EXAMPLE 20 (lS, 2R, 3R, 5R) -3- (Acetoxymethyl) -5- (4,5-dichloro-2-nitroanilino) -1,2-cyclopentanediyl diacetate Acetylated (IS, 4R) - [4- (4,5-dichloro-2-nitroanilino) -2-cyclopenten-1-yl] methanol (3.75 grams, 11.1 mmol) in pyridine-acetic anhydride as in Example 16. The crude product was leached from a column of silica gel with 2 percent methanol-chloroform, and solidified from ethyl acetate, to give (1S, 2R, 3R, 5R) -3- (acetoxymethyl) -5- (4,5-dichloro) diacetate -2-nitroanilino) -1,2-cyclopentanediyl as a yellow powder (5.13 grams, 100 percent), NMR identical to that of Example 1. This sample was crystallized from ethyl acetate-hexanes, to give the title as a yellow powder, mp 128-130 ° C; 1 H-NMR (DMSO-d 6) and mass spectrum (Cl) identical to those of Example 1; [a] 20589-95.8 °, [a] 20578-107 °, [a] 20546-165 ° (c = 0.259, methanol). Analysis calculated for C 18 H 20 N 2 Cl 2 O 8: C, 46.67; H, 4.35; N, 6.05; Cl, 15.31. Found: C, 46.74; H, 4.36; N, 5.96; Cl, 15.38. Example 21 (lS.2R, '3R, 5R) -3- (Acetoxymethyl) -5- (5,6-dichloro-lH-benzimidazol-1-yl) -1,2-cyclopentanediyl diacetate Diacetate was converted from , 2R, 3R, 5R) -3- (acetoxymethyl) -5- (4,5-dichloro-2-nitroanilino) -1,2-cyclopentanediyl (4.42 grams, 9.97 mmol) in the title compound as with the racemic sample described in Example 2. The crude product was chromatographed on silica gel with leaching by 5 percent methanol-chloroform, and the solvents were evaporated to give (1S, 2R, 3R, 5R) -3- diacetate ( acetoxymethyl) -5- (5,6-dichloro-lH-benzimidazol-1-yl) -1,2-cyclopentanediyl as a white solid foam from ethanol (4.0 grams, 90 percent); • "• H-NMR (DMSO-d6) and mass spectrum (Cl) identical to those of the racemate described in Example 2; [a] 20 558899 + 25.5 ' [a] 20578 + 26.7 °, [a] 20546 + 30.6 ° (c = 0.255, methanol). Analysis calculated for C 19 H 20 N 2 Cl 2 O 6: C, 51.49; H, 4. 55; N, 6.32; Cl, 16.00. Found: C, 51.33; H, 4.58; N, 16. 27; Cl, 15.90. Example 22 (1S.2R, 3R, 5R) -5- (5,6-Dichloro-1H-benzimidazol-1-yl) -3- (hydroxymethyl) -1,2-cyclopentanediol Diacetate was stirred (1S, 2R, 3R, 5R) -3- (α ce tox imetil) -5- (5,6-dichloro-lH-benzimidazol-1-yl) -1,2-cyclopentanediyl (0.96 grams, 2.17 mmol) and sodium carbonate (0.230 grams, 2.17 mmol) in water (3 milliliters) -ethanol (15 milliliters) -methanol (15 milliliters), at room temperature for 24 hours. The pH was adjusted to 7 with acetic acid, and the volatiles were removed in vacuo. The residual solid was formed in a paste with water (25 milliliters), and filtered. Residification from 2: 1 ethanol-methanol gave (SS, 2R, 3R, 5R) -5- (5,6-dichloro-1H-benzimidazol-1-yl) -3- (hydroxymethyl) -1, 2 -cyclopentanediol as a white powder (408 milligrams, 60 percent), mp 222-225 ° C; 1 H-NMR (DMS0-d6) d: 8.49, 8.09, and 7.96 (all s, 1 each, 3 benzimidazole CH), 5.04 (d, J = 7.0 Hz, 1, OH), 4.87 (t, J = 5.1 Hz, 1, CH2OH), 4.8-4.6 (m overlapping d in 4.76, J = 4.3 Hz, 2, NCH and OH), 4.25-4.10 (m, 1, OCH), 3.9-3.8 (m, 1, OCH) , 3.6-3.45 (m, 2, CH20), 2.45-2.25 (m, 1, CH), 2.2-2.0 (m, 1, CH), 1.85-1.65 (m, 1, CH); mass spectrum (Cl): 317 (M + l); [a] 20589-12.2 °, [a] 20578-12.9 °, [a] 20546-14.1 °, (c = 0.255, methanol). Analysis calculated for C 13 H 14 N C1203: C, 49.23; H, 4.45; N, 8.83; Cl, 22.36. Found: C, 49.25; H, 4.47; N, 8.83; Cl, 22.46. Example 23 (1S.2R.3R, 5R) -5- (2-Bromo-5,6-dichloro-1H-benzimidazol-1-yl) -3- (hydroxymethyl) -1,2-cyclopentanediol Diacetate was dissolved (1S, 2R, 3R, 5R) -3- (acet-oxymethyl) -5- (5,6-dichloro-1H-benzimidazol-1-yl) -1,2-cyclopentanediyl (2.00 grams, 4.51 mmol) in dry N, N-dimethylformamide ( 9 milliliters), and warmed to 90 ° C.

N-bromosuccinimide (1.62 grams, 9.02 millimoles) was added in four portions for 5 hours. The volatiles were evaporated in vacuo. The residue was chromatographed on silica gel, and the product was leached with 30-50 percent ethyl acetate-hexanes as a yellow crystal (1.00 grams, 43 percent); 1 H-NMR (DMS0-d6) consistent with the structure. This sample was deblocked with sodium carbonate (203 milligrams, 1.9 millimoles) in water (3 milliliters) -ethanol (15 milliliters) -methanol (15 milliliters), at room temperature for 5 hours. The pH was adjusted to 7 with acetic acid. The solution was evaporated to dryness in vacuo, and the residue was triturated with water to give a white powder, which was passed through chromatography. The leaching of a column of silica gel with 10-12 percent methanol-chloroform gave (S, 2R, 3R, 5R) -5- (2-bromo-5,6-dichloro-1H-benzimidazole-1- il) -3- (hydroxymethyl) -1,2-cyclopentanediol as a white powder after solidification from 1: 1 ethanol-methanol (410 milligrams, 54 percent), mp 212-215 ° C; 1 H-NMR (DMS0-d 6) and mass spectrum identical to those of the racemate described in Example 4; [a] 20589-31.2 °, [a] 20578-32.3o, [a] 205 6-37.3o (c = 0.260, methanol). Analysis calculated for C 13 H 13 N 2 BrCl 203: C, 39.43; H, 3.31; N, 7.07; total halogen as Cl, 26.86. Found: C, 39.62; H, 3.37; N, 7.02; total halogen as Cl, 26.75.

Example 24 (1S, 2R, 3R, 5R) -5-G5, 6-dichloro-2- (cyclopropylamino) -1H-benzimidazole-1-ill -3- (hydroxymethyl) -1,2-cyclopentanediol Diacetate was refluxed ( ÍS, 2R, 3R, 5R) -3- (acetoxymethyl) -5- (2-bromo-5,6-dichloro-lH-benzimidazol-1-yl) -1,2-cyclopentanediyl (500 milligrams, 0.958 mmol) in water: ethanol / 2: 1 (7.5 milliliters) with cyclopropylamine (0.66 milliliters, 9.6 mmol) under nitrogen for 18 hours. Thin layer chromatography (silica gel, 10 percent methanol-chloroform) showed complete conversion to a single spot with a lower Rf than the starting material. Sodium hydroxide IN (0.96 milliliters) was added, and the volatiles were evaporated. The residue was passed through chromatography on a silica gel evaporation column. The title compound was leached with 10 percent methanol-chloroform as a colorless crystal, which was solidified from water: ethanol / 2: 1 (5 milliliters), to give a white powder (207 milligrams, 59 percent , mp 116-118 ° C decomposition; 1 H-NMR (DMS0-d 6) d and mass spectrum: identical to those of the enantiomer described in Example 74; [a] 20589-12.2 '°, [a] 2057812.5 °, [a] 20546-13.5 ° (c = 0.312, methanol). Analysis calculated for C16H19N3C1203: C, 51.63; H, 5.15: N, 11.29; Cl, 19.05. Found: C, 51.37; H, 5.10; N, 11.16; Cl, 19.25.

Example 25 (lR, 4S) -4-amino-2-cyclopenten-l-methanol A mixture of (-) - (ÍS, 4R) -4-amino-2-cyclopentene-1-carboxylic acid (Chiroscience Ltd., Cambridge , England: 40.00 grams, 0.315 moles) in dry tetrahydrofuran (300 milliliters), was stirred in an ice bath, while IVM lithium aluminum hydride in tetrahydrofuran (Aldrich, 485 milliliters) was added for 1.5 hours. The temperature during this addition was not allowed to exceed 0 ° C. The mixture was brought to room temperature, and then refluxed for 1 hour, and refluxed for 2.5 hours. The mixture was allowed to cool to room temperature, and sodium fluoride (89.6 grams) was added, and stirring was continued for an additional 0.5 hours. The mixture was cooled (ice bath), and water (23 milliliters) was slowly added. Stirring was continued for 0.5 additional hours. The precipitate was filtered and extracted with 40 percent methanol-tetrahydrofuran (2 x 300 milliliters). Washing of the filtrate was concentrated in vacuo to a colorless oil, which darkened rapidly to air and light, and was used immediately (Example 16). This sample was dried at room temperature / 0.2 mm Hg until a pale yellow oil was obtained; 1 H-NMR (DMS0-d 6) identical to that of the enantiomer described in Example 22, d: 5.67 (m, 2, CH = CH), 3.8-3.7 (m, 1, CHN), 3.32 (d, J = 6.0 Hz, overlapped by interchangeable peak with wide D20 centered at 3.18, CH20, OH, NH2 and H20 in solvent), 2.68-2.56 (m, 1, Hl), 2.28-2.18 (m, 1, 1/2 CH2), 1.08 -0.98 (m, 1, 1/2 CH2); mass spectrum (Cl): 114 (M + 1); [a] 20589 + 55.0 °, [a] 20578 + 58.3 °, [a] 20546 + 67.4 °, [a] 20436 + 119 ° (c = 0.242, methanol). Analysis calculated for CgH- YNOFO.Sl H20: C, 60.69; H, 9.86; N, 11.80. Found: 61.12; H, 9.79; N, 11.38. Example 26 (! R, 4S) -r4- (4,5-dichloro-2-nitroani ino) -2-cyclopenten-l-i 1 * | me tanol The washing of the filtrate of Example 25 was concentrated, and terbutanol (400 milliliters) was added to the residual oil. This solution was used for the condensation with 1,2,4-trichloro-5-nitrobenzene (Aldrich, 71.3 grams, 0.315 moles as 97 percent) by the method of Example 10. The reaction mixture, after the evaporation of Volatiles in vacuo were chromatographed on a column of silica gel leached with 1: 1 hexanes-ethyl acetate and ethyl acetate. The rechromatography of the crude product on silica gel was carried out with leaching of 4-6% methanol-chloroform. Fractions containing the combined product yielded 58 grams of a reddish solid as the solvents evaporated. This solid was resolidified from ethyl acetate-hexanes to give (IR, 4S) - [4- (4,5-dichloro-2-nitroanilino) -2-cyclopenten-1-yl], ethanol as a yellow powder ( 34.5 grams, 36 percent from '(-) (1S, 4R) -4-amino-2-cyclopentene-1-carboxylic acid); p.f. 95-97 ° C; 1 H-NMR (DMSO-d 6) and mass spectrum (Cl) identical to those of the enantiomer described in Example 18; [a] 20589-195 °, [a] 20578-217 °, [a] 20546-326 ° (c = 0.350, methanol). Analysis calculated for C12H12N2C1203: C, 47.55; H, 3.99; N, 9.24; Cl, 23.39. Found: C, 47.56; H, 4.01; N, 9.25; Cl, 23.30. Continuous leaching of the column (above) gave an additional yellow powder (18.0 grams, 19 percent), whose ^ • H-NMR showed that the additional title compound was contaminated by approximately 15 percent of (1R, 4S) - [4- (2, 5-dichloro-4-nitroanilino) -2-cyclopenten-1-yl] methanol. Example 27 Diacetate of (1R, 2S, 3S, 5S) -3- (acetoxymethyl) -5- (4,5-dichloro-2-nitroanilino) -1,2-cyclopentanediyl and diacetate of (ÍS.2R.3S.5S) -3- (Acetoxymethyl) -5- (4,5-dichloro-2-nitroanilino) -1,2-cyclopentanediyl It was hydroxyl (IR, 4S) - [4 - (4, 5 Dichloro-2-nitroanilino) -2-cyclopenten-1-yl] methanol (17.00 grams, 56.1 mmol), and the triol mixture was acetylated as in Example 16. The crude red oil isolated after acetylation was passed through chromatography on silica gel and a mixture of title compounds was lixiviated with 2 percent methanol-chloroform. Fractional crystallization from ethyl acetate-hexanes gave diacetate of (IR, 2S, 3S, 5S) -3- (acetoxymethyl) -5- (4,5-dichloro-2-nitroanilino) -1,2-cyclopentanediyl as yellow needles in two crops (12.78 grams, 49 percent), mp 127-128 ° C; -? - NMR (DMSO-d6) and mass spectrum (Cl) identical to those of the racemic sample described in Example 1 and the enantiomer described in Example 55; [a] 20589 + 106 °, [a] 20578 + 119 °, [a] 20546 + 184 ° (c = 0. 275, methanol). Analysis calculated for C 18 H 20 N 2 Cl 2 O 8: C, 46.67; H, 4.35; N, 6.05; Cl, 15.31. Found: C, 46.74; H, 4.40; N, 6. 09; Cl, 15.22. Continuous fractional crystallization of the mother liquor content from ethyl acetate-hexanes gave (1S, 2R, 3S, 5S) -3- (acetoxymethyl) -5- (4,5-dichloro-2-nitroanilino) diacetate -1, 2-cyclopentanediyl as orange crystals (2.45 grams, 10 percent), mp 122-124 ° C; 1 H-NMR (DMS0-d 6). The evaporation of the combined mother liquors gave 9. 50 additional grams (40 percent) of a mixture of approximately 1: 1 (by 1 H-NMR) of the title compounds. Example 28 Diacetate of (IR, 28, 38, 58) -3- (Acetoxymethyl) -5- (5,6-dichloro-lH-benzimidazol-1-yl) -1,2-cyclopentanediyl Diacetate was converted from (IR, 2S, 3S, 5S) -3- (acetoxymethyl) '-5- (4,5-dichloro-2-nitroanilino) -1,2-cyclopentanediyl in the title compound as in Example 2. The crude product, after the Treatment with formic acid was carried out by chromatography on silica gel with leaching by means of 10 percent ethyl acetate-hexanes. Evaporation of the fractions containing the product left diacetate of (IR, 2S, 3S, 5S) -3- (acetoxymethyl) -5- (5,6-dichloro-lH-benzimidazol-1-yl) -1, 2- cyclopentanediyl as a white solid foam from ethyl acetate (1.85 grams, 95 percent); ^? - NMR (DMS0-d6) and mass spectrum (Cl) identical to those of the racemate described in Example 2 and the enantiomer described in Example 56; [a] 589-25.5 °, [a] 20578-27.0 °, [a] 20546-31.2 ° (c = 0.333, methanol). Analysis calculated for C19H 0N2Cl2O6 »0.1 EtOAc: C, 51.54; H, 4.64; N, 6.20; Cl, 15.68. Found: 51.29; H, 4. 69; N, 6.19; Cl, 15.91. Example 29 (18.2R.3S.5S) -5- (5,6-Dichloro-lH-benzimidazol-1-yl) -3- (hydroxymethyl) -1,2-cyclopentanediol and (IR, 28, 38, 58) -5 - (5,6-dichloro-lH-benzimidazol-1-yl) -3- (hydroxymethyl) -1,2-cyclopentanediol A mixture of about 1: 1 diacetate of (IR, 2S, 3S, 5S) -3- (acetoxymethyl) -5- (4,5-dichloro-2-nitroanilino) -1,2-cyclopentanediyl and diacetate (SS, 2R, 3S, 5S) -3- (acetoxymethyl) -5- (4,5-dichloro) -2-nitroanilino) -l, 2-cyclopentanediyl (4.30 grams, 9.28 mmol), was deacetylated with sodium carbonate (97 milligrams) in 1: 1: 1 water-ethanol-methanol (100 milliliters) at room temperature during 24 hours. The pH was adjusted to 7 with acetic acid, and the volatiles were removed in vacuo. The residual solid was extracted with methanol. The methanol filtrate was evaporated to dryness in vacuo. The residual solid was dissolved in methanol (55 milliliters) -water (20 milliliters), adjusted to a pH of 5 to 6 with sulfuric acid, and refluxed with iron powder (325 mesh, 99.9 percent, Aldrich, 5.18 grams, 93 milliequivalents) and iron sulfate heptahydrate (II) (Aldrich, 98 +%, 1.30 grams, 4.58 milliequivalents) for 4 hours. The solids were filtered and the washing of the ethanol filtrate was concentrated until an oil was obtained. Triethyl orthoformate (55 milliliters) and methanesulfonic acid (0.05 milliliters) were added to the oil, and the resulting solution was stirred at room temperature for 18 hours. Concentration in vacuo left an oil which was redissolved in IN hydrochloric acid (50 milliliters) -dioxane (5 milliliters). After 2.5 hours, the pH was adjusted to 7 with IN sodium hydroxide, and the volatiles were evaporated in vacuo. The residual solids were passed through chromatography on silica gel. The leaching with 10-12 percent methanol-chloroform gave fractions containing (ÍS, 2R, 3S, 5S) -5- (5,6-dichloro-lH-benzimidazol-1-yl) -3- (hydroxymethyl) - 1,2-cyclopentanediol, which was isolated as white crystals (540 milligrams, 18 percent) after crystallization from ethyl acetate-hexanes, mp. 201-2'02 ° C; -NRM (DMSO-d6) d: 8.42, 8.07, and 7.92 (all s, 1 each, 3 benzimidazole CH), 5.1-4.8 (m overlapping d in 5.02, J = 5.7 Hz, and d in 4.93, J = 3.9 Hz, total 3, NCH and 2 OH), 4.54 (t, J = 4.8 Hz, 1, OH), 4.2-4.0 (m, 2, 2 OCH), 3.75-3.45 (m, 2, 0CH2), 2.4- 1.9 (m, 3, CH2 and CH); mass spectrum (Cl): 317 (M + l); [a] 20589-61.4 °, [a] 20578-63.1 °, [a] 20546-72.9 ° (c = 0.350, methanol). Analysis calculated for C ^ H- ^ N ^ l-jO-j: C, 49.23; H, 4. Four. Five; N, 8.83; Cl, 22.36. Found: C, 49.20; H, 4.45; N, 8.78; Cl, 22.37. Continuous leaching of the column with 15-20 percent methanol-chloroform, gave fractions containing a mixture of the title compounds, followed by fractions containing only (1R, 2S, 3S, 5S) -5- (5, 6-dichloro-lH-benzimidazol-1-yl) -3- (hydroxymethyl) -1,2-cyclopentanediol, which was isolated as white crystals (605 milligrams, 21 percent) when crystallized from 10 percent methanol ethyl acetate, mp 221-222 ° C; 1H-JRMN (DMSO-d6) and mass spectrum (Cl) 317 (M + 1); [a] 20589 + 14.5 °, [a] 20578 + 15.2 °, [a] 20546 + 16.9 ° (c = 0.290, methanol). Analysis calculated for C13H14N2C1203: C, 49.23; H, 4.45; N, 8.83; Cl, 22.36. Found: C, 49.29; H, 4.46; N, 8.87; Cl, 22.26.

Example 30 Diacetate of (IR, 28.38, 58) -3- (Acetoxymethyl) -5- (2-bromo-5,6-dichloro-lH-benzimidazol-1-yl) -1,2-cyclopentanediyl Brominated diacetate of (1R, 2S, 3S, 5S) -3- (acetoxymethyl) -5- (5,6-dichloro-lH-benzimidazol-1-yl) -1,2-cyclopentanediyl (1.40 grams, 2.94 mmol) as in Example 3. The The volatiles were removed in vacuo, and the residue was chromatographed on silica gel. The crude product was leached with 20-30 percent hexane-ethyl acetate as a colorless oil. A chloroform solution of the oil was washed with water in order to remove contaminating succinimide. The chloroform solution was dried (sodium sulfate) and evaporated to dryness in vacuo to give the title compound as a soft solid foam from ethanol (760 milligrams, 50 percent), 1 H-NMR (DMSO-d6). ) and mass spectrum (Cl) identical to the racemate described in Example 3; [a] 20589 + 43.8 °, [a] 20578-45.2 °, [a] 20546 52.2 ° (c = 0.345, methanol). Analysis calculated for C19H19N2BrCl2O6 »0.05 EtOH: C, 43.74; H, 3.71; N, 5.34; total halogen as Cl, 20.28. Found: C, 43.74; H, 3.69; N, 5.35; total halogen as Cl, 20.41. Example 31 (IR, 28, 38, 58) -5- (2-Bromo-5,6-dichloro-lH-benzimidazole-li) -3- (hydroxymethyl) -1,2-cyclopentanediol Diacetate was deacetylated from (IR, 2S, 3S, 5S) -3- (acetoxymethyl) -5- (5,6-dichloro-1H-benzimidazol-1-yl) -1,2-cyclopentanediyl (660 milligrams, 1.26 mmol) as in Example 4, to give the title compound as a white powder after solidification from 1: 1 ethanol-methanol (415 milligrams, 83 percent), mp 213-216 ° C; 1 H-NMR (DMSO-d 6) and mass spectrum (Cl) identical to those of the racemate described in Example 4; [a] 578 + 35.9 °, [a] 20578 + 36.8o, [a] 20546 + 42.1 ° (c = 0.340, methanol). Analysis calculated for C 13 H 13 N 2 BrCl 203: C, 39.43; H, 3. 31; N, 7.07; total halogen as Cl, 26.86. Found: C, 39.48; H, 3.29; N, 7.00; total halogen as Cl, 26.90. Example 32 (IR, 28, 3S, 5S) -5- f 5, 6-dichloro-2- (cyclopropylamino) -1H-benzimidazol-1-ill-3- (hydroxymethyl) -1,2-cyclopentanediol was refluxed Diacetate (IR, 2S, 3S, 5S) -3- (acetoxymethyl) -5- (2-bromo-5,6-dichloro-lH-benzimidazol-1-yl) -1,2-cyclopentanediyl (500 milligrams, 0.958) millimoles) in water: ethanol / 2: 1 (7.5 milliliters) with cyclopropylamine (Aldrich's freshly opened ampule, 0.66 milliliters, 9.6 mmol) under nitrogen for 18 hours. Thin layer chromatography (silica gel, 10 percent methanol-chloroform) showed complete conversion to a single spot with a lower Rf than the starting material. Sodium hydroxide IN (0.96 milliliters) was added, and the volatiles were evaporated. The residue was passed through chromatography on a silica gel evaporation column. The title compound was leached with 10 percent methanol-chloroform as a colorless crystal, which was solidified from water: ethanol / 2: 1 (5 milliliters), to give a white powder (170 milligrams, 48 percent) ), pf 219-220 ° C; 1 H-NMR (DMSO-d 6) d: 7.64 and 7.46 (both s, 2, aromatic CH), 7.11 (m, 1, NH), 5.11 (t, J = 4.3 Hz, 1, OH), 4.77 (d, J = 7.0 Hz, 1, OH), 4.67 (d, J = 3.7 Hz, 1, OH), 4.65-4.30 (m, 2, OCH and NCH), 3.85-3.75 (m, 1, OCH), 3.7- 3.4 (m, 2, OCH2), 2.85-2.70 (m, 1, cyclopropyl NCH), 2.15-1.80 (m, 3, CH2 and CH of cyclopentane), 0.80-0.50 (m, 4, 2 CH2 of cyclopropyl); mass spectrum (Cl): 372 (M + 1); [a] 20589 + 13.4 °, [a] 20578 + 15.5 °, [a] 20546 + 16.9 ° (c = 0.277, methanol) [See Examples 26-28 and 30]. Analysis calculated for C16H19N3C1203: C, 51.63; H, 5.15; N, 11.29; Cl, 19.05. Found: C, 51.36; H, 5.06; N, 11.25; Cl, 19.16. Example 33 (IR, 28, 3S, 58) -5- f5,6-dichloro-2- (isopropylamino) -1H-benzimidazole-l-ill-3- (hydroxymethyl) -1,2-cyclopentanediol Diacetate was refluxed of (IR, 2S, 3S, 5S) -3- (acetoxymethyl) -5- (2-bromo-5,6-dichloro-lH-benzimidazol-1-yl) -1,2-cyclopentanediyl (1.00 grams, 1.92 mmol) ) in ethanol (10 milliliters with isopropylamine (1.6 milliliters, Fluka) under nitrogen for 24 hours, a second portion of isopropylamine (0.80 milliliters) was added, and reflux was continued for an additional 4 hours. After dissolving in ethanol, IN sodium hydroxide (1.90 milliliters) was added and the volatiles were again evaporated, the residue was chromatographed on a column of silica gel.The title compound was leached with 10% methanol. ethyl acetate-100 as a colorless crystal.The concentration of a solution in ethanol gave the title compound as a white solid foam (360 milligrams , 46 percent.) This sample was solidified by trituration with 95 percent water-5 percent methanol, to give the title compound as a white powder (96 percent), p.f. 137-138 ° C; 1H-JRMN (DMSO-d6) < S 7.60 and 7.39 (both s, 2, aromatic CH), 6.64 (d, J = 7.4 Hz, 1, NH), 5.14 (t, J = 4.3 Hz, 1, OH), 4.81 (d, J = 7.3 Hz , 1, OH), 4.70 (d, J = 3.5 Hz, 1, OH), 4.70-4.50 (m, 1, NCH), 4.50-4.30 (m, 1, OCH), 4.10-4.00 (m, 1, NCH cyclopropylamino), 3.9-3.75 (m, 1, OCH), 3.70-3.50 (m, 2, OCH2), 2.20-1.80 (m, 3, CH2 and CH of cyclopentane), 1.24 (d, J = 6.6 Hz , 6.2 CH3); mass spectrum (Cl): 374 (M + 1); [a] 20589-3.72 °, [a] 20578-2.60 °, [a] 20546-2.23 °, [a] 20436-9.67 °, [a] 20365-51.7 ° (c = 0.269, methanol). [See Examples 16-18 and 20). Analysis calculated for C16H21N3C1203 «1.3 H20: C, 48.32; H, 5.98; N, 10.57; Cl, 17.83. Found: C, 48.08; H, 5.91; N, 10.41; Cl, 18.13. Example 34 (±) - (IR *, 28 *, 38 », 58») -5- (5,6-dichloro-2-amino-lH-benzimidazol-1-yl) -3- (hydroxymethyl) -1, 2-cyclopentanediol Diacetate of (±) - (IR *, 2S *, 3S *, 5S *) -3- (acetoxymethyl) -5- (2-bromo-5,6-dichloro-1H-benzimidazole-1- was dissolved. il) -1,2-cyclopentanediyl (750 milligrams, 1.44 millimoles) in ethanol (10 milliliters). Hydrazine hydrate (55 percent, 0.41 milliliter, 7.2 mmol) was added, and the solution was refluxed for 2 hours. The volatiles were evaporated, and the residual white solid was re-solidified from ethanol-water, and stirred with Raney nickel (pre-equilibrated under hydrogen) in methoxyethanol (20 milliliters) for 30 minutes. The catalyst was filtered, and the filtrate was made slightly basic with aqueous sodium hydroxide, to complete the removal of the acetate groups. The solution was neutralized, and the volatiles were evaporated. The residual solid was recrystallized from ethanol-water to give the title compound as a pale pink solid (97 milligrams, 20 percent), m.p. 283-284 ° C decomposition; - '"H-NMR (DMSO-d6) d: 7.61 and 7.30 (both s, 2, aromatic CH), 6.65 (br s, 2, NH2), 5.07 (t, J = 4.3 Hz, 1, OH), 4.80 (d, J = 7.0 Hz, 1, OH), 4.66 (d, J = 3.7 Hz, 1, OH), 4.65-4.50 (m, 1, NCH), 4.45-4.30 (m, 1, OCH), 3.90-4.80 (m, 1, OCH), 3.70-3.40 (two m, 2, 0CH2), 2.20-1.80 (m, 3, CH2 and CH of cyclopentane), mass spectrum (Cl): 332 (M + l ) [See Examples 1 to 3] Analysis calculated for C13H15N3C1203: C, 47.01; H, 4.55; N, 12.65; Cl, 21.35, Found: C, 46.72; H, 4.60; N, 12.46; Cl, 21.08. Example 35 (±) - (lR *, 2R », 4S *) - 2- (2-cyclopropylamino-5,6-dichloro-1H-benzimidazol-1-yl) -4- (hydroxymethyl) cyclopentanol Acetate was reacted (±) - (IR *, 2R *, 4S *) -4- (acetoxymethyl) -2- (2-bromo-5,6-dichloro-lH-benzimidazol-1-yl) -cyclopentyl (500 milligrams, 1.50 millimoles ) with cyclopropylamine (0.73 milliliters) in the manner of Example 32.

The crude product was passed through chromatography on silica gel, and the title compound was leached with 5 percent methanol-ethyl acetate as a colorless crystal, which was solidified from ethyl acetate-hexanes to give a powder white (180 milligrams, 48 percent), mp 251-253 ° C; XH-NMR (DMSO-d6) d: 7.54 and 7.45 (both s, 2, aromatic CH), . 04 (d, J = 5.1 Hz, 1, OH), 4.97 (t, J = 4.7 Hz, 1, OH), 4. 60-4.50 and 4.50-4.03 (amos m, 1 each, NCH and OCH), 3.50 (m, 2, OCH2), 2.80 (m, 1, CH), 2.35-2.10 (m, 1, CH), 2.05 -1.80 (m, 3, CH2 and CH of cyclopentane), 1.80-1.60 (m, 1, CH), 0.80- 0.50 (1 m, 4, 2CH2 of cyclopropyl); Mass spectrum (Cl): 356 (M + l). [See Examples 5-7]. Analysis calculated for C16H19N3C1202: C, 53.97; H, 5.34; N, 11.80; Cl, 19.91. Found: C, 53.72; H, 5.42; N, 11.52; Cl, 19.64. Example 36 (±) - (lR * .2S * .3S *, 5S ») - 5-r5,6-dichloro-2- (cyclobutylamino) -lH-benzimidazol-1-yl] -3- (hydroxymethyl) -1 , 2-cyclopentanediol Diacetate of (±) - (IR *, 2S *, 3S *, 5S *) -3- (acetoxymethyl) -5- (2-bromo-5,6-dichloro-1H-benzimidazole-1) was dissolved. -yl) -1,2-cyclopentanediyl (500 milligrams, 0.958 millimoles) in absolute ethanol (7 milliliters) and cyclobutylamine (0.41 milliliters, 4.8 millimoles). The solution was refluxed under nitrogen for 18 hours. The volatiles were evaporated, and the residue was stirred in medium methanol saturated with ammonia at 0 ° C (20 milliliters) for 18 hours. The volatiles were removed in vacuo, and the residue was crystallized from ethanol-water to give the title compound as a white solid, m.p. 250 ° C decomposition; XH-NMR (DMSO-d6) d 7.61 and 7.38 (both s, 1 each, aromatic CH), 7.07 (d, J = 7.4 Hz, 1, NH), 5.15 (t, J = 3.9 Hz, 1, OH ), 4.81 (d, J = 7.3 Hz, 1, OH), 4.71-4.45 (m overlapping d in 4.71, J = 3.5 Hz, total 2, OH and NCH), 4.40-4.30 (m, 2, OCH and NCH) ), 3.82-3.80 (m, 1, OCH), 3.72-3.42 (both, 1 each, OCH2), 2.32-1.67 (three m, 9, 4CH2 and CH); mass spectrum (Cl): 386 (M + l). [See Examples 5 to 7]. Analysis calculated for C17H21N3C1203 »0.15 H2O« 0.05 C2H5OH: C, 52.49; H, 5.56; N, 10.74; Cl, 18.12. Found: C, 52.34; H, 5.47; N, 10.52; CL, 17.99.

Example 37 (±) - (lR ».2S * .3S» .5S *) - 5-rs, 6-dichloro-2- (l-acetidinyl) -lH-benzimidazol-l-yl] -3- (hydroxymethyl) -1,2-cyclopentanediol Diacetate of (±) (IR *, 2S *, 3S *, 5S *) -3- (acetoxymethyl) -5- (2-bromo-5,6-dichloro-lH-benzimidazole- was dissolved. 1-yl) -1,2-cyclopentanediyl (500 milligrams, 0.958 mmol) in ethanol (7 milliliters). Acetidine (Aldrich, 250 milligrams, 4.4 millimoles as 98 percent) was added, and the solution was refluxed under nitrogen for 48 hours. Methanolic ammonia (saturated at 0 ° C, 20 milliliters) was added to the cooled solution, and this solution was stirred for an additional 18 hours. The volatiles were evaporated, the residue redissolved in ethanol (10 milliliters), and IN sodium hydroxide (0.96 milliliters) was added. The volatiles were evaporated, and the residual solids were triturated with water (3 milliliters) and filtered. Resolidification of the solid from acetonitrile-methanol gave the title compound as a white powder (146 milligrams, 41 percent), m.p. 221-222 ° C; 1 H-NMR (DMS0-d6) d 7.78 and 7.53 (both s, 1 each, 2, aromatic CH), 5.05 (t, J = 4.3 Hz, 1, OH), 4.91 (d, J = 5.3 Hz, 1 , OH), 4.59 (d, J = 3.7 Hz, 1, OH), 4.45-4.40 (m, 2, OCH and NCH), 4.25-4.15 (, 4, 2 CH2M), 3.82-3.79 (m, 1, OCH), 3.66-3.43 (both m, 1 each, OCH2), 2.40-2.32 (m, 2, CH2), 2.03-1.95 (m, 3, CH2 and NCH); mass spectrum (Cl): 372 (M + l). [See Examples 8-10].

Analysis calculated for C-L6HJ9N3C1203: C, 51.63; H, 5.14; N, 11.29; Cl, 19.05. Found: C, 51.45; H, 5.10; N, 11.27; Cl, 18.96. Example 38 (±) - (lR ».2S» .3R *, 5R ») - 5-r5,6-dichloro-2- (cyclopropylamino) -1H-benzimidazol-1-ill -3- (hydroxymethyl) -1, 2-Cyclopentanediol Diacetate of (±) - (IR *, 2S *, 3R *, 5R *) -3- (acetoxymethyl) -5- (2-bromo-5,6-dichloro-1H-benzimidazole) was refluxed. 1-yl) -1,2-cyclopentanediyl (Example 39, 1.00 grams, 1.87 mmol), cyclopropylamine (Aldrich, 1.7 milliliters, 24 mmol), and absolute ethanol (10 milliliters) under nitrogen for 48 hours. The reaction was cooled and IN sodium hydroxide (1.2 milliliters) was added. The volatiles were evaporated in vacuo, and the residual oily solid was passed through chromatography on silica gel. Leaching with 5 percent methanol-ethyl acetate gave fractions containing a white powder (200 milligrams). Recrystallization from 1: 1 of water-ethanol gave (+/-) - (IR *, 2S *, 3R *, 5R *) -5- [5,6-dichloro-2- (cyclopropylamino) -1H- benzimidazol-1-yl] -3- (hydroxymethyl) -1,2-cyclopentanediol as white crystals (180 milligrams, 40 percent); p.f. > 250 ° C; 1 H-NMR (DMS0-d 6) < S 7.70 (m, 1, NH), 7.62 and 7.39 (both s, 1 each, 2 benzimidazole CH), 5.77 (br s, 1, OH), 5.13 (d, J = 5.3 Hz, í, OH), 4.95 - 4.80 (m, 1, CHN), 4.48 (t, J = 4.7 Hz, CH2OH), 4.2 - 4.0 (m, 2, 2 OCH), 3.7 - 4.0 (m, 2, OCH2), 2.9 - 2.65 ( m, 1, OCH), 2.2-1.8 (m, 3, CH2 and CH); mass spectrum (Cl): 372 (M + l). [See Examples 10 to 14]. Analysis calculated for C16H19N3C1203: C, 51.63; H, 5.14; N, 11.29; Cl, 19.05. Found: C, 51.53; H, 5.18; N, 11.22; Cl, 18.97. Example 39 (±) - (IR *, 28 *, 3R », 58 *) -5-f5, 6-dichloro-2- (cyclopropylamino) -1H-benzimidazol-1-yl / -3-methyl-1, 2-cyclopentanediol Part A. (±) (lS », 2R», 3R *, 5R ») - 5- (5,6-dichloro-lH-benzimidazol-1-yl) -3- (hydroxymethyl) -1,2-cyclopentanediol Diacetate was dissolved (±) - (IR *, 2S *, 3S *, 5S *) -3- (acetoxymethyl) -5- (5,6-dichloro-lH-benzimidazol-1-yl) -1,2-cyclopentanediyl (Example 2 , 3.00 grams, 6.77 millimoles) in methanol (100 milliliters). Methanol saturated with ammonia was added at 0 ° C (100 milliliters), and the solution was stirred at room temperature overnight. The volatiles were evaporated in vacuo, and the residual solid was formed in a paste with water, and filtered to give the title compound as a tan powder (2.02 grams, 94 percent). Part B. (±) - (1R ».2S», 3R », 5S *) -5- (5,6-dichloro-lH-benzimidazol-1-yl) -3-? Odo-l, 2-cyclopentanediol dissolved (±) - (lS *, 2R *, 3R *, 5R *) - 5- (5, 6-dichloro-lH-benzimidazol-1-yl) -3- (hydroxymethyl) -1,2-cyclopentanediol (Part A, 2.00 grams, 6.31 mmol) in dry dimethylformamide (15 milliliters) under nitrogen, and cooled (bath of ice) while a solution of methyltriphenoxyphosphonium iodide (Aldrich, 3.27 grams, 6.94 millimoles) in dry dimethylformamide (15 milliliters) was added dropwise over 20 minutes. Stirring was continued in the ice bath for an additional 30 minutes, and then at room temperature for 18 hours. The volatiles were evaporated in vacuo, and the residue was chromatographed on silica gel. The product was leached with 2 percent methanol-chloroform, to give, after evaporation of the solvents, a pale yellow powder (750 milligrams, 28 percent); 1 H-NMR (DMS0-d6) d 8.51, 8.08, and 7.97 (all s, 1 each, 3, benzimidazole CH), 5.20 (d, J = 6.7 Hz, 1, OH), 5.04 (d, J = 4.9 Hz, 1, OH), 4.8-4.6 (m, 1, NCH), 4.3-4.2 (m, 1, OCH), 3.8-3.7 (m, 1, OCH), 3.6-3.4 (m, 2, CH21) , 2.55-2.40 (m, overlapping solvent CH), 2.35-2.20 (m, 1, CH), 1.75-1.50 (m, 1, CH). Part C. Diacetate of (±) - (lR », 2S» .3R * .5S ») -5- (5,6-dichloro-lH-benzimidazol-l-yl) -3-methyl-l, 2-cyclopentanediyl Stirred (±) - (IR *, 2S *, 3R *, 5S *) -5- (5,6-dichloro-lH-benzimidazol-1-yl) -3-iodo-1,2-cyclopentanediol (Part B) , 0.73 grams, 1.71 millimoles) in ethanol (200 milliliters) with 5 percent Pd on carbon (140 milligrams) with triethylamine (0.24 milliliters) under hydrogen (3.5 kg / cm2) on a Parr shaker for 7.5 hours. The catalyst was filtered (Celite), and the ethanol filtrate was evaporated to a white solid. To this solid was added pyridine (15 milliliters) and acetic anhydride (1.3 milliliters). The resulting solution was stirred at room temperature for 18 hours. The volatiles were evaporated, and the residual oil was dissolved in chloroform (50 milliliters). The chloroform solution was extracted with aqueous sodium bicarbonate, and dried (sodium sulfate). Evaporation of the chloroform left the title compound as a yellow crystal (560 milligrams, 85 percent); ^? - NMR (DMS0-d6) d 8.61, 8.15, and 7.97 (all s, 1 each, 3 benzimidazole CH), 5.60-5.45 (m, 1, OCH), 5.20-4.95 (m, 2, OCH and NCH), 2.50-2.15 (m, 3, CH2 and CH), 2.09 and 1.95 (both s, 3 each, 2 OAc), 1.20 (d, J = 6.5 Hz, 3, CHCH3). Part D: Diacetate of (±) - (lR *, 2S *, 3R * .5S *) - 5- (2-bromo-5,6-dichloro-lH-benzimidazol-1-yl) -3-methyl-1, 2 -cyclopentanediyl Diacetate of (±) - (IR *, 2S *, 3R *, 5S *) -5- (5,6-dichloro-1H-benzimidazol-1-yl) -3-methyl-1, 2 - was dissolved. cyclopentanediyl (Part C, 550 milligrams, 1.43 mmol) in dry tetrahydrofuran (15 milliliters). N-bromosuccinimide (520 milligrams, 2.92 millimoles) was added, and the resulting solution was refluxed vigorously for 10 minutes. An additional portion of N-bromosuccinimide (100 milligrams) was added, and reflux was continued for an additional 5 minutes. At this point, thin layer chromatography (silica gel plates developed with 5 percent methanol-chloroform) showed that the starting material had become an ultraviolet absorbing spot of a slightly higher Rf. The reaction mixture was quenched by cooling (ice bath), and diluted with chloroform (50 milliliters). This solution was washed with water and dried (sodium sulfate). The evaporation left a yellow solid, which was passed through chromatography on silica gel. The title compound was leached with 5 percent methanol-chloroform, and triturated in ethyl acetate to give a white powder (460 milligrams, 68 percent), m.p. 235-236 ° C decomposition; 1H-gRMN (DMS0-d6) < S: 8.38 and 7.97 (both s, 1 each, 2 benzimidazole CH), 5.75-5.65 (, 1, OCH), 5.2-5.0 (m, 2, OCH and NCH), 2.11 (s) overlapped by 2.2-2.05 (, total 6, OAc with CH2 and CH), 1.95 (s, 3, OAc), 1.22 (d, J = 6.3 Hz, 3, CHCH3); mass spectrum (Cl): 463 (M + l). Part E. (t) (1R *, 2S », 3R *, 5S») -5-.T5, 6-dichloro-2- (cyclopropylamino) -lH-benzimidazole-1-ill-3-methyl-2, 2- Cyclopentanediol Diacetate of (±) (IR *, 2S *, 3R *, 5S *) -5- (2-bromo-5,6-dichloro-1H-benzimidazol-1-yl) -3-methyl- was added to reflux. 1, 2-cyclopentanediyl (Part D, 350 milligrams, 0.75 mmol) and cyclopropylamine (Aldrich, 0.53 milliliters), in methoxyethanol (5 milliliters), for 5 hours. Sodium hydroxide IN (0.75 milliliters) was added to the cooled reaction mixture, and the volatiles were evaporated in vacuo. The residue was passed through chromatography on silica gel. The product was leached with 5 percent methanol-chloroform. Recrystallization from methanol-ethyl acetate gave (±) - (1R *, 2S *, 3R *, 5S *) -5- [5,6-dichloro-2- (cyclopropylamino) -1H-benzimidazole-1- il] -3-methyl-l, 2-cyclopentanediol as white crystals (170 milligrams, 64 percent); p.f. 231-233 ° C; 1 H-NMR (DMSO-d 6) 5: 7.48 and 7.39 (both s, 1 each, 2 benzimidazole CH), 7.10 (m, 1, NH), 4.83 (d, J = 5.9 Hz, a, OH), 4.74 (d, J = 5.1 Hz, 1, OH), 4.5-4.3 (m, 2, NCH and OCH), 3.7-3.6 (m, 1, OCH), 2.85-2.7 (m, 1, CHNH), 2.1- 1.8 (M, 2, CH2 and CH), 0.8-0.5 (m, 4, 2 CH2 of cyclopropyl); mass spectrum (Cl): 356 (M + l). [See Examples 1 and 2], Analysis calculated for C16H19N3C1202: C, 53.95; H, 5.38; N, 11.80; Cl, 19.90. Found: C, 53.75; H, 5.45; N, 11.71; Cl, 19.98. Example 40 (IR, 28.38.5S) -5-r2- (terbutylamino) -5,6-dichloro-lH-benzimidazol-1-ill -3- (hydroxymethyl) -1,2-cyclopentanediol A solution of (IR, 2S, 3S , 5S) -5- (2-bromo-5,6-dichloro-lH-benzimidazol-1-yl) -3- (hydroxymethyl) -1,2-cyclopentanediol (500 milligrams, 1.26 mmol), was stirred in terbutylamine ( Aldrich, 98 percent, 20 milliliters) in a Parr pump maintained at 148 ° C (oil bath) for 48 hours. The pump was cooled, and the resulting pale yellow solution was diluted with ethanol containing IN sodium hydroxide (1.2 milliliters). The volatiles were evaporated in vacuo, and the residue was chromatographed on silica gel. The title compound was leached with 10 percent methanol-chloroform as a colorless oil. The oil was dissolved in absolute ethanol, concentrated to an oil, and triturated with water (3 milliliters), to give (IR, 2S, 3S, 5S) -5- [2- (terbutylamino) -5,6- dichloro-lH-benzimidazol-1-yl] -3- (hydroxymethyl) -1,2-cyclopentanediol as a white powder (303 milligrams, 61 percent), mp: collapses to a crystal at 116-150 ° C; XH-NMR (DMSO-d6) d: 7.63 and 7.43 (both s, 2, aromatic CH), 6.15 (s, 1, NH), 5.08 (t, J = 4.3 Hz, 1, OH), 4.85 (d, J = 7.4 Hz, 1, OH), 4.71 (d, J = 3.8 Hz, 1, OH), 4.7-4.5 (m, 1, NCH), 4.45-4.3 (, 1, OCH), 3.80 (m, 1 , OCH), 3.7-3.4 (m, 2, OCH2), 2.2-1.85 (m, 3, CH2 and CH of cyclopentane), 1.47 (s, 9, 3 CH3); mass spectrum (Cl): 388 (M + 1); [a] 20589-4.0 °, [a] 20578-4.3 °, [a] 20546-6.0 °, [a] 20436-22.'6 °, [a] 20365-82.1 ° (c = 0.420, methanol). [See Examples 25-28, 30, and 31]. Analysis calculated for C 17 H 23 N 3 Cl 2 O 3 »0.40 H 20: C, 51.63; H, 6.07; N, 10.62; Cl, 17.93. Found: C, 51.50; H, 5.99; N, 10.54; Cl, 17.96. Example 41 (±) - (IR * .2S * .3S *, 5S *) -5- T2- (terbutylamino) -5,6-dichloro-lH-benzimidazole-1-in -3- (hydroxymethyl) -1,2- Cyclopentanediol A solution of (±) - (IR *, 2S *, 3S *, 5S *) -5- (2-bromo-5,6-dichloro-lH-benzimidazol-1-yl) -3- (hydroxymethyl) - 1,2-cyclopentanediol (750 milligrams, 1.44 mmol), was stirred in terbutylamine (Aldrich, 98 percent, 25 milliliters), in a Parr pump maintained at 90 ° C (oil bath) for 6 days. The volatiles were evaporated in vacuo, and the residual solids were refluxed in ethanol (30 milliliters) with aqueous dimethylamine (Aldrich, 40 percent, 2 milliliters) for 1 hour. The volatiles were evaporated, and the residual solids were passed through chromatography on silica gel. Leaching with 10 percent methanol-ethyl acetate gave the title compound as a colorless crystal. Solidification from water gave (±) - (IR *, 2S *, 3S *, 5S *,) -5- [2- (terbutylamino) -5,6-dichloro-lH-benzimidazol-1-yl] - 3- (hydroxymethyl) -1,2-cyclopentanediol as a white powder (150 milligrams, 26 percent); p.f. 130-132 ° C; 1 H-NMR (DMS0-d6) identical to that of the enantiomer described in Example 30. [See Examples 1 to 4]. Analysis calculated for C17H23N3Cl2O3 «0.65 H2O» 0.07 C2H5OH: C, 51.18; H, 5.94; N, 10.47; C, 17.63. Found: C, 51.34; H, 6.06; N, 10.37; Cl, 17.58. Example 42 (±) - (IR * .28 * .38 *, 58 *) -5-r5, 6-dichloro-2- (isopropylamino) -1H-benzimidazol-1-yl] - (hydroxymethyl) -1,2 -cyclopentanediol Reflux (±) _ (IR *, 2S *, 3S *, 5S *) -3- (acetoxymethyl) -5- (2-bromo-5,6-dichloro-1H-benzimidazole-1) diacetate was refluxed. -yl) -1,2-cyclopentanediyl (750 milligrams, 1.44 millimoles) in ethanol (10 milliliters) with isopropylamine (1.22 milliliters, Aldrich) under nitrogen for 18 hours. A second portion of isopropylamine (1.22 milliliters) was added, and the reflux was continued for an additional 24 hours. The volatiles were evaporated, the residue redissolved in ethanol, IN sodium hydroxide (1.44 milliliters) was added, and the volatiles were again evaporated. The residue was passed through chromatography on a column of silica gel. The title compound was leached with 10 percent methanol-chloroform as a colorless crystal. The crystal was crystallized from ethyl acetate-hexanes, to give (±) - (1R *, 2S *, 3S *, 5S *) - 5- [5,6-dichloro-2- (isopropylamino) -1H- benzimidazol-1-yl] -3- (hydroxymethyl) -1, 2-cyclopentanediol as white crystals (305 milligrams, 57 percent); p.f. 213-214 ° C; 1 H-NMR (DMS0-d6) identical to that of the enantiomer described in Example 23. [See Examples 1 to 4]. Analysis calculated for C16H21N3C1203: C, 51.35; H, 5.66; N, 11.23; Cl, 18.95. Found: C, 51.27; H, 5.69; N, 11.17; Cl, 18.88.

Claims (15)

1. NOVELTY OF THE INVENTION Having described the foregoing invention, it is considered as a novelty, and therefore, the content of the following is claimed as property: CLAIMS 1. A compound of the formula (I) or (1-1): wherein: R1 is H, CH3, or CH2OH; R2 is H or OH; R3 is H or OH; or R2 and R3 together form a bond; R 4 is amino, cyclopropylamino, cyclobutylamino, isopropylamino, terbutylamino, or -NR 8 R 9, wherein R 8 and R 9, together with the nitrogen atom to which they are attached, form a 4, 5, or 6 membered heterocyclic ring; R5 is H, and R6 and R7 are Cl, excluding the compound (+) - (IR *, 2S *, 3S *, 5S *) -5- [5,6-dichloro-2- (cyclopropylamino) -1H-benzimidazole -1-yl] -3- (hydroxymethyl) -1,2-cyclopentanediol, provided that at least one of R1, R2, and R3 is or contains OH; and pharmaceutically acceptable derivatives thereof.
2. 2. A compound according to claim 1, characterized in that R2 is OH.
3. 3. A compound according to claim 2, characterized in that R 4 is cyclopropylamino, isopropylamino, or terbutylamino.
4. 4. A compound according to claim 3, characterized in that R4 is isopropylamino or terbutylamino.
5. 5. A compound according to claim 1 of formula (IA) or (IA-1): wherein R2 is H or OH; R 4 is amino, cyclopropylamino, isopropylamino, terbutylamino, or -NRβR 9, wherein R 8 and R 9, together with the nitrogen atom to which they are attached, form a 4, 5, or 6 membered heterocyclic ring; R5 is H; and R6 and R7 are Cl, and excluding the compound (+) - (1R *, 2S *, 3S *, 5S *) -5- [5,6-dichloro-2- (cyclopropylamino) -1H-benzimidazole-1- il] -3- (hydroxymethyl) -1,2-cyclopentanediol, and pharmaceutically acceptable derivatives thereof.
6. 6. A compound according to claim 5, characterized in that R4 is cyclopropylamino, isopropylamino, or terbutylamino; Rs is H; and R6 and R7 are both Cl; and pharmaceutically acceptable derivatives thereof.
7. 7. A compound according to claim 6, characterized in that R4 is isopropylamino or terbutylamino.
8. 8. A compound according to claim 1, which is selected from: (IR, 2S, 3S, 5S) -5- [5,6-dichloro-2- (cyclopropylamino) -lH-benzyl -dazol-1-yl] -3- (hydroxymethyl) -1,2-cyclopentanediol; (IR, 2S, -3S, 5S) -5- [5,6-dichloro-2- (isopropylamino) -lH-benzimidazol-1-yl] -3- (hydroxymethyl) -1,2-cyclopentanediol; (±) - (IR *, 2S *, - 3S *, 5S *) - 5- (5,6-dichloro-2-amino-1H-benzimidazol-1-yl) -3- (hydroxymethyl) -1, 2 -cyclopentanediol; (±) - (IR *, 2R *, 4S *) -2- (2-cyclopropylamino-5,6-dichloro-lH-benzimidazol-1-yl) -4- (hydroxymethyl) cyclopentanol; (±) - (IR *, 2S *, 3S *, 5S *) -5- [5,6-dichloro-2- (cyclobutylamino) -lH-benzimidazol-1-yl] -3- (hydroxymethyl) -1, 2-cyclopentanediol; (±) - (1R *, 2S *, 3S *, 5S *) - 5- [5,6-dichloro-2- (l-acetidinyl) -lH-benzimidazol-1-yl] -3- (hydroxymethyl) - 1,2-cyclopentanediol; (±) - (IR *, 2S *, 3R *, 5R *) -5- [5,6-dichloro-2- (cyclopropylamino) -lH-benzimidazol-1-yl] -3- (hydroxymethyl) -1, 2-cyclopentanediol; (±) - (IR *, 2S *, 3R *, 5S *) -5- [5,6-dichloro-2- (cyclopropylamino) -lH-benzimidazol-1-yl] -3-methyl-1, 2- Cyclopen-tannediol; (IR, 2S, 3S, 5S) -5- [2- (tert-butylamino) -5,6-dichloro-lH-benzimidazol-1-yl] -3- (hydroxymethyl) -1,2-cyclopentanediol; (±) - (IR *, 2S *, 3S *, 5S *) -5- [2- (tert-butylamino) -5,6-dichloro-lH-benzimi-dazol-1-yl] -3- (hydroxymethyl) - 1,2-cyclopentanediol; (±) - (IR *, 2S *, 3S *, 5S *) - 5- [5,6-dichloro-2- (isopropylamino) -1H-benzimidazol-1-yl] -3- (hydroxymethyl) -1, 2-cyclopentanediol; (SS, 2R, 3R, 5R) -5- [5,6-dichloro-2- (isopropylamino) -lH-benzimide-zol-1-yl] -3- (hydroxymethyl) -1,2-cyclopentanediol; (1S, 2R, -3R, 5R) -5- [2- (tert-butylamino) -5,6-dichloro-lH-benzimidazol-1-yl] -3- (hydroxymethyl) -1,2-cyclopentanediol; (±) - (IR *, 2S *, 3S *, 5S *) - 5- [5,6-dichloro-2- (1-acetidini-1) -lH-benzimidazol-1-yl] -3- (hydroxymethyl) - 1, 2-cyclopentanediol; (IR, 2S, 3S, 5S) -5- [5,6-dichloro-2- (1-acetidinyl) -lH-benzimidazol-1-yl] -3- (hydroxymethyl) -1,2-cyclopentanediol; and (SS, 2R, 3R, 5R) -5- [5,6-dichloro-2- (1 -acetidinyl) -lH-benzimidazol-1-yl] -3- (hydroxymethyl) -1,2-cyclopentanediol, and pharmaceutically acceptable derivatives thereof.
9. 9. A method for the treatment of a viral herpes infection in a subject, which comprises treating the subject with a therapeutically effective amount of at least one compound of the formula (I) or (1-1) (as defined in claim 1), or a pharmaceutically acceptable derivative thereof.
10. 10. A method according to claim 9, characterized in that the viral herpes infection is a cytomegalovirus infection.
11. 11. A method according to claim 9 or claim 10, characterized in that this compound is selected from: (IR, 2S, 3S, 5S) -5- [5,6-dichloro-2- (cyclopropylamino) -lH-benzimidazol-1-yl] -3- (hydroxymethyl) -1,2-cyclopentanediol; (IR, 2S, 3S, 5S) -5- [5,6-dichloro-2- (isopropylamino) -lH-benzimidazol-1-yl] -3- (hydroxymethyl) -1,2-cyclopentanediol; (±) - (IR *, 2S *, 3S *, 5S *) -5- (5,6-dichloro-2-amino-lH-benzimidazol-1-yl) -3- (hydroxymethyl) -1, 2- cyclopentanediol; (±) - (1R *, 2R *, 4S *) -2- (2-cyclopropylamino-5,6-dichloro-lH-benzimidazol-1-yl) -4- (hydroxymethyl) cyclopentanol; (±) - (IR *, -2S *, 3S *, 5S *) - 5- [5,6-dichloro-2- (cyclobutylamino) -lH-benzimide-zol-1-yl] -3- (hydroxymethyl) -1,2-cyclopentanediol; (±) - (lR *, - 2S *, 3S *, 5S *) -5- [5,6-dichloro-2- (1-acetidinyl) -lH-benzimidazol-1-yl] -3- (hydroxymethyl) -1, 2-cyclopentanediol; (±) - (IR *, 2S *, - 3R *, 5R *) -5- [5,6-dichloro-2- (cyclopropylamino) -lH-benzyl-idazol-1-yl] -3- (hydroxymethyl) - 1,2-cyclopentanediol; (±) - (1R *, 2S *, - 3R *, 5S *) -5- [5,6-dichloro-2- (cyclopropylamino) -lH-benzimidazol-1-yl] -3-methy1-1, 2 -cyclopentanediol; (IR, 2S, 3S, 5S) -5- [2- (tert-butylamino) -5,6-dichloro-lH-benzimidazol-1-yl] -3- (hydroxy-methyl) -1,2-cyclopentanediol; (±) - (1R *, 2S *, 3S *, 5S *) - 5- [2- (terbutylamino) -5,6-dichloro-lH-benzimidazol-1-yl] -3- (hydroxymethyl) - 1,2-cyclopentanediol; (±) - (IR *, 2S *, 3S *, 5S *) -5- [5,6-dichloro-2- (isopropylamino) -lH-benzimidazol-1-yl] -3- (hydroxymethyl) -1, 2-cyclopentanediol; (SS, 2R, 3R, 5R) -5- [5,6-dichloro-2- (isopropylamino) -lH-benzimidazol-1-yl] -3- (hydroxymethyl) -1,2-cyclopentanediol; (SS, 2R, 3R, 5R) -5- [2- (tert-butylamino) -5,6-dichloro-lH-benzimidazol-1-yl] -3- (hydroxymethyl) -1,2-cyclopenta-nodiol; (±) - (lR *, 2S *, 3S *, 5S *) - 5- [5,6-dichloro-2- (1-acetidinyl) -lH-benzimidazol-1-yl] -3- (hydroxymethyl) - 1,2-cyclopentanediol; (IR, 2S, 3S, 5S) -5- [5,6-dichloro-2- (1-acetidinyl) -1H-benzimidazol-1-yl] -3- (hydroxymethyl) -1,2-cyclopentanediol; and (SS, 2R, 3R, 5R) -5- [5,6-dichloro-2- (1-acetidinyl) -lH-benzimidazol-1-yl] -3- (hydroxymethyl) -1,2-cyclopentanediol, and pharmaceutically acceptable derivatives thereof.
12. 12. The use of one or more of the compounds according to claim 1, in the preparation of a medicament for the treatment of viral infections, particularly infections by hepatitis B virus and cytomegalovirus.
13. 13. Pharmaceutical formulations comprising at least one compound of the formula (I) or (1-1) (as defined in claim 1), or a pharmaceutically acceptable derivative thereof, together with at least one pharmaceutically available carrier or excipient acceptable.
14. 14. A pharmaceutical formulation according to claim 13, characterized in that said compound is selected from: (IR, 2S, 3S, 5S) -5- [5,6-dichloro-2- (cyclopropylamino) - lH-benzimidazol-1-yl] -3- (hydroxymethyl) -1,2-cyclopentanediol; (IR, 2S, 3S, 5S) -5- [5,6-dichloro-2- (isopropylamino) -lH-benzimidazol-1-yl] -3- (hydroxymethyl) -1,2-cyclopentanediol; (±) - (IR *, 2S *, 3S *, 5S *) - 5- (5,6-dichloro-2-amino-lH-benzimidazol-1-yl) -3- (hydroxymethyl) -1,2- cyclopentanediol; (±) - (IR *, 2R *, 4S *) -2- (2-cyclopropylamino-5,6-dichloro-lH-benzimidazol-1-yl) -4- (hydroxymethyl) cyclopentanol; (±) - (IR *, 2S *, 3S *, 5S *) -5- [5,6-dichloro-2- (cyclobutylamino) -1H-benzimidazol-1-yl] -3- (hydroxymethyl) -1, 2-cyclopentanediol; (±) - (lR *, 2S *, 3S *, 5S *) - 5- [5,6-dichloro-2- (l-acetidinyl) -lH-benzimi-dazol-l-yl] -3- (hydroxymethyl) ) -1, 2-cyclopentanediol; (±) - (IR *, 2S *, 3R *, 5R *) -5- [5,6-diclors-2- (cyclopropylamino) -1H-benzimidazol-1-yl] -3- (hydroxymethyl) -1, 2-cyclopentanediol; (±) - (IR *, 2S *, 3R *, 5S *) -5- [5,6-dichloro-2- (cyclopropylamino) -1H-benzimidazol-1-yl], - 3-methyl-1, 2 -cyclopentanediol; (1R, 2S, -3S, 5S) -5- [2- (tert-butylamino) -5,6-dichloro-lH-benzimidazol-1-yl] -3- (hydroxymethyl) -1,2-cyclopentanediol; (±) - (IR *, 2S *, 3S *, 5S *) - 5- [2- (terbutylamino) -5,6-dichloro-lH-benzyl-idazol-1-yl] -3- (hydroxymethyl) -1 , 2-cyclopentanediol; (±) - (IR *, 2S *, 3S *, 5S *) -5- [5,6-dichloro-2- (isopropylamino) -lH-benzimidazol-1-yl] -3- (hydroxymethyl) -1, 2-cyclopentanediol; and pharmaceutically acceptable derivatives thereof.
15. 15. A process for the preparation of compounds of formulas (I) and (1-1) (as defined in claim 1), alone or in combination with their mirror image enantiomers, and pharmaceutically acceptable derivatives thereof, which comprises (A) reacting: 0 the mirror image enantiomer thereof, with a) either a compound of the formula RC02H, wherein R4 is H, alkyl 1 to 4 carbon atoms, or perfluoroalkyl of 1 to 4 carbon atoms, or a compound of the formula R 4 C (OR) 3, wherein R 4 is H, alkyl of 1 to 4 carbon atoms, or perfluoroalkyl of 1 to 4 carbon atoms, and R is alkyl of 1 to 4 carbon atoms, to form a compound of the formula (IA) or (1-1), wherein R 4 is H; or b) cyanogen bromide to form a compound of the formula (IA) or (IA-1), wherein R 4 is NH 2; (B) a) converting a compound of the formula (IA) or (IA-1) wherein R4 is hydrogen, into a further compound of the formula (IA) or (IA-1), wherein R4 is a removable group or b) converting a compound of the formula (IA) or (IA-1) in which R 4 is Cl, Br, or I, into a further compound of the formula (IA) or (IA-1), wherein R 4 is amino, or a substituted amino group-NRβR9 as defined above; or (C) reacting a compound of the formula: (wherein R4, RS, RS and R7 are as previously defined herein), or a functional equivalent thereof, with a compound of the formula: wherein R1, R2, and R3 are as defined above, and L is a releasable group, to form a compound of the formula (IA) or (IA-1), wherein R4 is hydrogen, halogen, or -ISJR8R9, and optionally converting a compound of the formula (IA) or (IA-1) into a pharmaceutically acceptable derivative thereof.