WO2006105728A1

WO2006105728A1 - Diarylheptanoids, preparation and the use thereof

Info

Publication number: WO2006105728A1
Application number: PCT/CN2006/000596
Authority: WO
Inventors: Jianmin Yue; Zhixin Liao; Shengping Yang; Chengqi Fan; Lei Dong; Yan Wu
Original assignee: Shanghai Institute Of Materia Medica, Chinese Academy Of Sciences
Priority date: 2005-04-05
Filing date: 2006-04-04
Publication date: 2006-10-12
Also published as: CN1686091A; CN100531725C

Abstract

The present invention provides diarylheptanoids , such as diphenyl heptanone , diphenyl heptenone , diphenyl heptanedione , and the use of pharmaceutical composition thereof for treating infection caused by helicobacter pylori or the diseases associated with ulcer in intestine and stomach . They have good effect on helicobacter pylori (Hp), and can restore mucous membrane lesions caused by helicobacter pylori .

Description

Diphenylheptanone compound, preparation method and use thereof

The invention belongs to the technical field of pharmaceutical application, and particularly relates to the use of diarylheptanoids compounds (such as diphenylheptanone, diphenylheptenone and diphenylheptanedione) and pharmaceutical compositions thereof. , especially in the pharmaceutical field. Background technique

Chronic active gastritis, gastric ulcer and duodenal ulcer, gastric MALT lymphoma and gastric cancer are diseases that seriously endanger human health and life. Medical research has confirmed that these diseases are associated with Helicobacter pylori (Hp) infection. According to the data, more than 50% of the world's population is infected with Helicobacter pylori, especially in developing countries, reaching 60-80% among adults. In 1994, the International Agency for Research on Cancer (IARC) listed Hp as a human Class I carcinogen. At present, anti-endocrine drugs and antibiotic combination therapy are used at home and abroad to treat Hp infection. However, due to large side effects, patients are poorly tolerated, and drug resistance is produced, and the efficacy and application are affected. Therefore, finding new ways to combat Hp infection and treatment of related diseases has become a research topic of concern.

However, to date, there have been no reports on anti-Helicobacter pylori infection or treatment of intestinal and gastric ulcers with diphenylheptanone compounds (eg diphenylheptanone, dipyridylheptenone and diphenylheptanedione) 4 rumors about sexually transmitted diseases.

Based on the screening of a large number of compounds for anti-HP activity, the present invention has found for the first time that diphenylheptanone compounds (such as: dipyridyl heptyl steel, diphenylheptenone and diphenylheptanedione) have surprisingly Good anti-Helicobacter pylori (Hp) effect, and has a repairing effect on gastric mucosal damage caused by Helicobacter pylori. Summary of the invention It is an object of the present invention to provide a class of diphenylheptanone compounds.

Another object of the present invention is to provide such a compound for the treatment of active gastritis caused by Helicobacter, particularly against Helicobacter pylori, gastric erosion, gastric ulcer (with or without complications such as gastric bleeding, gastric perforation) and ten Application of drugs for duodenal ulcer.

The compound of the present invention is represented by the following formula (I):

RR ² , R ³ , R ⁴ , R ⁵ and R ⁶ are each independently H, a decyloxy group or a hydroxy group.

The present invention further provides a pharmaceutical composition for anti-Helicobacter pylori infection or for treating a disease associated with intestinal and gastric ulcer, the pharmaceutical composition comprising a therapeutically effective amount of a diphenylheptanone compound having the structure of formula (I) And a pharmaceutically acceptable carrier.

The diphenylheptanone compound of the present invention exhibits a good anti-Helicobacter pylori effect in both in vitro and in vivo tests, and has a repairing effect on gastric mucosal damage caused by Helicobacter pylori, and has significant inhibition of Helicobacter pylori ( Hp) activity; Moreover, the eradication rate of Helicobacter pylori is significantly better than the current "triple therapy", and it is highly promising to become a new anti-Helicobacter pylori or a drug for treating intestinal and gastric ulcer-related diseases.

Specific compounds of the invention are

Examples of the compounds of the invention are shown in Table 1 below:

Table 1: fi number R ¹ to R ⁶ RX

0 ox

1 R^R^R^ II R ⁴ = R = R ⁶ =HH

0 ox

2 Me

II

〇 0 ox

3 R ^1: =R ² =R ³ = R ⁴ = H, R ⁵ =OH, R ⁶ =OMe H

II 0 ox

4 ER ² =R ³ = R ⁴ = R ⁶ =H, R =O 〇H Me

0 ox

5 R^R^R ³ ^ R ⁴ = R ⁵ = R ⁶ =H Me

_R i 0 ox

6 = _R 2 = _R 3 _{= R} 4 _{= R} 6 = _H , _R 5 _=0H H

0

7 R'=R ² =R ³ = R ⁴ = R ⁵ = R ⁶ =H

8 R^R^R ³ ^ R ⁴ = H, R ⁵ =03⁄4 R ⁶ =OMe ―

0

9 R^R^R ³ ^ R ⁴ = R ⁶ =H, R ⁵ =OH ―

0

10 R ^l = R ³ = R ⁴ = R ⁶ = H, R ² = R ⁵ = OH -

0

11 R ¹⁼ R ⁴ = H, R ² =R ⁵ =OH ₅ R ³ =R ⁶ =OMe -

0

12 R ^J =R ² =R ³ = H, R ⁴ =R ⁵ =OH, R ⁶ =OMe ―

0

13 R]= H, R ² =R ⁵ =OH, R ³ = R ⁴ =R ⁶ =OMe -

0

14 R ⁴ = H, R ² =R ⁵ =OH, ^! =R ³ = R ⁶ =OMe -

0

15 R'=R ⁴ =R ⁶ = H, R ² = R ⁵ =OH, R ³ =OMe -

0 0

16 R'=R ² =R ³ = R ⁴ = R ⁵ = R ⁶ =H -

0 0

17 R'= R ⁴ = R ⁵ = R ⁶ =H, ² =OH ₅ R ³ = OMe - Physicochemical properties and data of the compounds in Table 1:

Compound 1: 5-hydroxy-1,7-diphenyl-3-heptanone (dihydroyashabushiketol), molecular weight: 282, molecular formula: C ₁₉ 3⁄4 ₂ 0 ₂ , its trait is white needle crystal, mp. 48.5-49.5 °C, soluble in ethanol;

Compound 2 : 1-phenyl-5-decyloxy-7-(4-hydroxy-3-indolylphenyl)-3-heptanone (7-(4-hydroxy-3-methoxyphenyl)-5-methoxy - 1 -phenyl-3 -heptanone ) , Molecular Weight: 342, Molecular Formula: C ₂₁ _3⁄4 ₆ 0 ₄ , its trait is a colorless oil, soluble in ethanol;

'Compound 3: 1-phenyl-5-hydroxy-7-(4-hydroxy-3-indolylphenyl)-3-heptanone (5-hydroxy-7-(4-hydiOxy-3-methoxyphenyl)- L-phenyl-3-heptanone), molecular weight: 328, molecular formula: C ₂₀ H ₂₄ O ₄ , its trait is colorless needle crystal mp. 60.0-61.5 ° C, soluble in ethanol;

Compound 4 : 1-phenyl-5-hydroxy-7-(4-hydroxyphenyl)- 1 -phenyl-3 -heptanone, molecular weight: 298, the molecular formula is: C ₁₉ H ₂₂ 0 ₃ , its trait is a colorless oil, soluble in ethanol;

Compound 5 : 1,7-diphenyl-5-methoxyphenyl-heptanone, molecular weight: 296 , molecular formula: C _2Q H ₂₄ 0 ₂ , its trait is a colorless oil, soluble in ethanol;

Compound 6 : 1-phenyl-5-hydroxy-7-(4-hydroxyphenyl)-3-heptanone (5-hydroxy-7-(4-hydroxyphenyl)- 1 -phenyl-3 -heptanone ) , Molecular weight: 298, the molecular formula is: C ₁₉ H ₂₂ 0 ₃ , its trait is a colorless oil, soluble in ethanol;

Compound 7: 1,7-diphenyl-4-heptan-3-one (l,7-diphenyl-4-hepten-3-one), molecular weight: 264, molecular formula: C ₁₉ H ₂ . 0, its trait is a colorless oil, soluble in ethanol;

Compound 8: 1-phenyl-7-(4-hydroxy-3-indolylphenyl)-4-hepten-3-one (7-(4-hydi'oxy) -3 -methoxyphenyl)- 1 -phenyl-4-hepten-3 -one ), molecular weight: 310, molecular formula: C ₂ . H ₂₂ 0 ₃ , its trait is a colorless oil, soluble in ethanol;

Compound 9: 1-phenyl-7-(4-hydroxyphenyl)-4-hepten-3-one (7-(4-hydroxyphenyl)-1(phenyl-4-hepten-3-one), Molecular Weight: 280, the molecular formula is: C ₁₉ H ₂ Q0 ₂ , the trait is a colorless oil, soluble in ethanol;

Compound 10: 1,7-bis(4-hydroxyphenyl)-4-hepten-3-one (1,7-bis(4-hydroxyphenyl)-4-hepten-3-one ), Molecular Weight: 296, Molecular Formula It is: C ₁₉ H ₂₀ O ₃ , its trait is colorless oil, soluble in ethanol;

Compound 11: 1,7-bis(4-hydroxy-3-indolylphenyl)-4-glycos-3-one (Gingerenone A), molecular weight: 356, molecular formula: C ₂₁ H ₂₄ 0 ₅ , Its trait is a colorless oil, soluble in ethanol; Compound 12: 1-phenyl-7-(4,5-dihydroxy-3-methoxyphenyl)-4-heptyl-3-one (7 -(4,5-dihydroxy-3 -methoxyphenyl)- 1 -phenyl-4-hepten-3 -one ) , Molecular Weight: 326 , Molecular Formula: C ₂₀ _3⁄4 ₂ O ₄ , Its Properties are Light Yellow Oil, Soluble In ethanol;

Compound 13: 1-(4-hydroxy-3-indolylphenyl)-7-(4-hydroxy-3,5-dimethoxyoxyphenyl)-4-hepten-3-one (gingenone B), Molecular weight: 386, molecular formula: C ₂₂ H ₂₆ 0 ₆ , its trait is light yellow oil, soluble in ethanol;

Compound 14: 1-(4-Hydroxy-3,5-dimethoxyoxyphenyl)-7-(4-hydroxy-3-indolylphenyl)-4-hepten-3-one (isogingerenone B) , molecular weight: 386, molecular formula: C ₂₂ 3⁄4 ₆ 0 ₆ , its trait is light yellow oil, soluble in ethanol;

Compound 15: 1-(4-Hydroxy-3-indolylphenyl)-7-(4-hydroxyphenyl)-4-hepten-3-one (Gingerenone C), Molecular Weight: 326, Molecular Formula: C _2Q H ₂₂ 0 ₄ , its trait is light yellow oil, soluble in ethanol;

Compound 16: 1,7-diphenyl-3,5-heptanedione (1,7-diphenyl-3,5-heptanedione), Sub-quantity: 280, the molecular formula is: C ₁₉ H ₂ . 0 ₂ , its trait is a colorless oil, soluble in ethanol; Compound 17: 1-(4-hydroxy-3-indolylphenyl)-7-phenyl-3,5-heptanedione ( l- (4-hydroxy-3-methoxyphenyl)-7-phenyl-3,5-heptanedione ) , Molecular Weight: 326 , Molecular Formula: C ₂₀ H ₂₂ O ₄ , its trait is a colorless oil, soluble in ethanol.

Diphenylheptanone compounds are widely used, not only from the general chemical extraction and separation methods of Zingiberaceae, such as: 10Kg gingeraceae - Yunnan grasshopper (Dalbergine) Alpinia b / /araca/yx ) The seeds are extracted with 95% ethanol to obtain a crude extract, and then partitioned with ethyl acetate and water, and then the ethyl acetate fraction is purified by a silica gel column and a reversed-phase silica gel column to obtain compound 1-17; Prepared by organic synthesis, such as: 1-iodo-4-phenyl-2-butanone and 3-phenylpropanal, catalyzed Aldol condensation with 9-BBN and 2,6-lutidine at room temperature, 84 The yield of % gave Compound 1. Specific Procedures The compounds were prepared according to the specific separation methods and synthetic methods disclosed in the following literature:

1. Chen, J.; Karchesy, J. J.; Gonzalez-Laredo, R. F. Phenolic diary lheptenones from Alniis rubra bark, Planta Med. 1998, 64 (1), 74-75.

2. Ali, MS; Tezuka, Υ·; Banskota, AH; Kadota, S. Blepharocalyxins CE, three new dimeric diary lheptanoids, and related compounds from the seeds of Alpinia blepharocalyx, J. Nat. Prod. 2001, 64 (4) , 491-496.

3. Ali, M. S.; Tezuka, Y; Banskota, A. H.; Kadota, S. Six new diary lheptanoids from the seeds of Alpinia blepharocalyx, J. Nat. Prod. 2001, 64 (3), 289-293.

4. Solladie, G; Ziani-Cherif, C.; Jesser, F. Asymmetric synthesis of (-) (R) yashabushiketol, Tetrahedron Lett. 1992, 33, 931-934.

5. Miyashita, M,; Hoshino, M,; Yoshikoshi, A. An expedient synthesis of natural diary lheptanoids using the organicselenium-mediated reduction of epoxy Ketone, Chem. Lett. 1990, 791-794.

6. Zhao, H.; Wu, Y. L. Chiral synthesis of yashabushiketol, Chin. Chem. Lett.

1994, 5, 367-370.

7. Mukaiyama, T.; Takuwa, T.; Yamane, Κ·; Imachi, S. Stereoselective Crossed Aldol Reaction via Boron Enolates Generated from α-Iodo Ketones and 9-Borabicyclo [3.3.1 ]nonane Bull. Chem. Soc. Jpn. 2003, 76, 813-823.

Pharmaceutical composition containing a compound of the invention:

The pharmaceutical compositions of the present invention comprise a compound of the invention and a pharmaceutically acceptable carrier in a safe, effective dosage range. "Safe, effective dose" means that the amount of the compound is sufficient to significantly improve the condition without causing serious side effects. The safe and effective dosage of the pharmaceutical composition of the present invention can be easily determined by those skilled in the art according to the prior art, depending on the age, condition, course of treatment, and the like of the subject to be treated. The pharmaceutical composition preferably comprises from 0.1% by weight to 99.9% by weight of the compound of the present invention, and a pharmaceutically acceptable carrier (having a carrier content of from 0.1% by weight to 99.9% by weight). Among them, the compound content is more preferably from 0.5% by weight to 10% by weight, and the carrier content is more preferably from 90% by weight to 99.5% by weight.

"Pharmaceutically acceptable carrier means: one or more compatible solid or liquid fillers or gel materials which are suitable for human use and which must be of sufficient purity and of sufficiently low toxicity." Capacitance, as used herein, means that the components of the composition are capable of blending with the compounds of the present invention and with each other without significantly reducing the efficacy of the compound. Some examples of pharmaceutically acceptable carriers are sugars (such as glucose, sucrose, lactose, etc.), starch (such as corn starch, potato starch, etc.), cellulose and its derivatives (such as sodium carboxymethyl cellulose, ethyl fiber). Sodium, cellulose acetate, etc., gelatin, talc, solid lubricants (such as stearic acid, barium stearate), 4 bismuth sulphate, vegetable oils (such as soybean oil, sesame oil, peanut oil, olive oil, etc.), polyol (eg propylene glycol, glycerin, mannitol, sorbitol, etc.), emulsifier (such as Tween®), wetting agents (such as sodium lauryl sulfate), colorants, flavoring agents, stabilizers, antioxidants, preservatives, pyrogen-free water, etc. The choice of the carrier of the pharmaceutical composition of the present invention depends on the mode of administration of the pharmaceutical composition, and can be formulated into general pharmaceutical tablets, granules, capsules, oral liquid preparations and general pharmaceutical preparations. DETAILED DESCRIPTION OF THE INVENTION Example 1: Pharmacological Test

1. The role of anti-Helicobacter pylori in vitro:

A certain dose of diphenylheptanone compound was added to the respective quantitative nutrient agar medium, mixed evenly, poured into a sterile plate, inoculated with 10 ⁷ CFU/mL in logarithmic growth of Helicobacter pylori, micro need After 5 days of oxygen culture, the blind scraping was transferred to the drug-free medium. At 37. C microaerobic culture

For 4-5 days, the presence or absence of Helicobacter pylori growth was observed to determine the respective minimum bactericidal concentration (MBC). Table 2. Effect of the diphenylheptanone compounds of the invention against Helicobacter pylori (Hp) in vitro against minimum bactericidal concentrations (MBCs) of different Hp strains (Hp-Sydney strain 1 (Hp, SSI) Hp-F44 Hp-Hudong positive control (曱肖唑) 1.0 1.0 1.0 Compound 1-6 12.5 25.0 12.5 Compound 7-15 12.5 12.5 25.0 Compound 16-17 25.0 25.0 25.0 wherein Hp-Sydney strain 1 (Hp, SSl) is Standard strain; Hp-F44 and Hp- Hudong are clinical bacteria

2. In vivo pharmacological test of 5-hydroxy-1,7-diphenyl-3-heptanone (Compound 1) in mice:

50 secondary C ₅₇ BL/6 mice, weighing 20-25 g, were intragastrically administered with a certain strain of Helicobacter pylori (Hp SSI) to achieve Hp colonization in vivo. Hp-planted mice were divided into blank control group and positive The drug control group and the 5-hydroxy-1,7-diphenyl-3-heptanone (100 mg/kg) group. There are six groups of 10 each. The positive control group used the triple therapy currently used by Western medicine: omeprazole 5.2 mg/kg, clarithromycin 65 mg/kg and metronidazole 104 mg/kg; the blank control group was the control solvent. Each group was orally administered, and continuous administration was carried out for 14 days. After stopping the administration for 30 days, the mice were dissected in a sterile room and examined as follows:

(1) Rapid urease test and bacterial culture method: Examination of eradication of Helicobacter pylori (Hp)

(2) Histological examination: The recovery of gastric mucosal injury (including erosion, glandular hyperplasia and adenoma formation) caused by Helicobacter pylori infection is examined, that is, the effective treatment rate.

Table 3 In vivo pharmacological results of 5-hydroxy-1,7-diphenyl-3-heptanone

Hp eradication rate (%) effective treatment rate (%)

Positive control group 60 30 recovery, 70 still moderate and

Severe glandular hyperplasia

Blank control group 0 100 gastric pyloric mucosal epithelial gland enlargement

Health, the formation of adenoma, nuclear fission is more common.

5-hydroxy-1,7-diphenyl-3-glycol 100 80 basically returned to normal, 20 still light

@同度腺体。

3. In vivo pharmacological test of 1,7-diphenyl-4-hepten-3-one (Compound 7) in mice:

50 secondary C ₅₇ BL/6 mice, weighing 20-25 g, were intragastrically administered with Helicobacter pylori (Hp-F44), which was fixed in bacteria, to achieve Hp colonization in vivo. Hp-planted mice were divided into a blank control group, a positive drug control group, and a 1,7-diphenyl-4-heptan-3-one group (100 mg/kg) group. There are six groups, 10 in each group. The positive control group was treated with the current triple therapy of Western medicine: omeprazole 5.2 mg/kg, clarithromycin 65 mg/kg and nitroxazole 104 mg/kg; the blank control group was the control solvent. Each group was orally administered, and continuous administration was carried out for 14 days. After 30 days of cessation of administration, dissect the small in a sterile room Rat, check the following:

(1) Rapid urease test and bacterial culture method: Check the eradication rate of Helicobacter pylori (Hp).

Table 4 In vivo pharmacological results of 1,7-diphenyl-4-hepten-3-one

Hp eradication rate (%) effective treatment rate (%)

Positive control group 60 30 recovery, 70 still moderate and

Severe glandular hyperplasia

Blank control group 0 100 gastric pyloric mucosal epithelial gland enlargement

Health, the formation of adenoma, nuclear fission is more common.

5-Hydroxy-1,7-diphenyl-3-glycol 100 90 returned to normal, and 10 still had moderate ketone glandular hyperplasia.

Pharmacological test of the drug composition (Mouth of the Moon) in mice:

50 secondary C ₅₇ BL/6 mice, weighing 20-25 g, were intragastrically administered with a certain strain of Helicobacter pylori (Hp SSI) to achieve Hp colonization in vivo. Hp-planted mice were divided into a blank control group, a positive drug control group, and a 0.6% oral solution (15 mL/kg) group. There are six groups, 10 in each group. The positive control group used the triple therapy currently used by Western medicine: omeprazole 5.2 mg/kg, clarithromycin 65 mg/kg and nitroxazole 104 mg/kg; the blank control group was the control solvent. Each group was orally administered, and continuous administration was carried out for 14 days. After stopping the administration for 30 days, the mice were dissected in a sterile room and examined as follows:

(2) Histological examination: The recovery of gastric mucosal damage (including erosion, glandular hyperplasia and adenoma formation) caused by Helicobacter pylori infection is examined, that is, the effective treatment rate.

Table 5 In vivo pharmacological results of oral liquid Group Hp eradication rate (%) Effective treatment rate (%)

Positive control group 60 30 recovered, 70 still had moderate and severe glandular hyperplasia

The blank control group 0 100 gastric pyloric mucosal epithelial gland hyperplasia, the formation of adenoma, nuclear fission is more common.

5-hydroxy-1,7-diphenyl-3-100 80 returned to normal, and 20 still had mild glandular hyperplasia. Hepone

The pharmaceutical composition containing the diphenylheptanone compound of the present invention is prepared by a method for preparing a pharmaceutical tablet, a granule, a capsule, or an oral solution. The proportions of the compositions of the following examples are all in weight percent.

Example 2: Preparation of medicinal tablets: The following amounts of diphenylheptanone compound were mixed with the additive, and 10% pregelatinized starch slurry was used as a binder, wet granulation, drying, and adding appropriate amount. The magnesium stearate is mixed and compressed into tablets. 5-hydroxy-1,7-diphenyl-3-heptanone (Compound 1) 7.5 g; Hydroxypropylcellulose 120 g; Microsilica gel 30 g; Pregelatinized starch 20 g; Magnesium stearate; 1000 sheets.

Example 3: Preparation of medicinal tablets: 5-hydroxy-1,7-diphenyl-3-heptanone (Compound 1) 18 g; Hydroxypropyl cellulose 120 g; Microsilica gel 30 g; Pregelatinized starch 20 g; Hard Magnesium oleate; mixed evenly, using 10% pre-gelatinized starch slurry as binder, wet granulation, drying, adding appropriate amount of magnesium stearate, and pressing into 1000 pieces.

Example 4: Preparation of granules: 5-hydroxy-1,7-diphenyl-3-heptanone (Compound 1) 15 g; sucrose 250 g; hydroxypropylcellulose 120 g; microsilica gel 30 g; citric acid, hydrogencarbonate The amount of sodium is mixed; the above composition is uniformly mixed, and an appropriate amount of 70% ethanol is used as a wetting agent, wet granulation, sieving, drying, and subpacking to prepare 200 bags of granules.

Example 5: Preparation of a capsule: 5-hydroxy-1,7-diphenyl-3-heptanone (Compound 1) 15 g; Hydroxypropyl cellulose 120g; micro-silica gel 30g; citric acid, sodium bicarbonate amount; mix the above composition evenly, use appropriate amount of 70% ethanol as humectant, wet granulation, sieving, drying, adding appropriate amount of stearic acid Magnesium, mixed evenly, and made into 1000 hard plastic bottles.

Example 6: Preparation of an anthraquinone: In 85 g of 5-hydroxy-1,7-diphenyl-3-heptanone (Compound 1), add citric acid, sodium hydrogencarbonate, stearic acid, and mix well. Milled into 300-400 mesh granules and packaged into 500 hard gelatin capsules.

Example 7: Preparation of oral liquid: Take an appropriate amount of distilled water, add 8 g of polysorbate-80 to prepare a solution, and then add 5-hydroxy-1,7-diphenyl-3-heptanone (compound 1) lg while heating. Stirring to dissolve, in addition, 8g of sucrose, a proper amount of preservative dissolved in distilled water, slowly added to the above solution with stirring, add distilled water to 1000mL, mix, cool, filter, dispense into 100, sterilize, Oral solution.

Example 8: Preparation of oral liquid: Take an appropriate amount of distilled water, add 50 g of polysorbate-80 to prepare a solution, and then add 5-hydroxy-1,7-diphenyl-3-heptanone (Compound 1) 6 g while heating. Stirring to dissolve, in addition, 50g of sucrose, a proper amount of preservative dissolved in distilled water, slowly added to the above solution with stirring, add distilled water to 1000mL, mix, cool, filter, dispense into 10Q, sterilize, Oral solution.

Example 9: Preparation of oral liquid: Take an appropriate amount of distilled water, add 600 g of polysorbate-80 to prepare a solution, and then add 5-hydroxy-1,7-diphenyl-3-heptanone (Compound 1) 100 g while heating. Stirring to dissolve, in addition, 100g of sucrose, a proper amount of preservative dissolved in distilled water, slowly added to the above solution with stirring, add distilled water to 1000mL, mix, cool, filter, dispense into 100, sterilize, Oral solution.

Example 10: Preparation of concentrated solution: 280 g of polysorbate-80 was added, and 200 g of 1,7-diphenyl-4-hepten-3-one (compound 7) was added thereto, and the mixture was stirred to be uniform, and a preservative was added. Appropriate amount is dissolved in distilled water, slowly added to the above mixture under stirring, distilled water is added to 500 mL, mixed, cooled, filtered, dispensed into 50 portions, and sterilized to obtain a concentrated liquid. The above examples are merely illustrative of the compounds of the present invention, the preparation methods of the compositions, and the results of the pharmacological experiments, but various modifications and changes can be made thereto without departing from the spirit and scope of the present invention. All such modifications are intended to be included within the scope of the appended claims.

Claims

Claim

1. A class of diphenylheptanone compounds represented by the following formula,

Ελ R ² , R ³ , R ⁴ , R ⁵ and R ⁶ are each independently H, oxime or hydroxy.

2. A compound according to claim 1 which is selected from the group consisting of: 1) 5-hydroxy-1,7-diphenyl-3-heptanone;

2) 1-phenyl-5-nonyloxy-7-(4-hydroxy-3-indolylphenyl)-3-heptanone;

3) 1-phenyl-5-hydroxy-7-(4-hydroxy-3-indolylphenyl)-3-heptanone;

4) 1-phenyl-5-hydroxy-7-(4-hydroxyphenyl)-3-heptanone;

5) 1,7-diphenyl-5-decyloxy-3-heptanone;

6) 1-phenyl-5-hydroxy-7-(4-hydroxyphenyl)-3-heptanone; '

7) 1,7-diphenyl-4-hepten-3-one;

8) 1-phenyl-7-(4-hydroxy-3-methoxyphenyl)-4-hepten-3-one;

9) 1-phenyl-7-(4-hydroxyphenyl)-4-hepten-3-one;

10) 1,7-bis(4-hydroxyphenyl)-4-hepten-3-one;

11) 1,7-bis(4-hydroxy-3-methoxyphenyl)-4-heptazone-3-one;

12) 1-phenyl-7-(4,5-dihydroxy-3-indolylphenyl)hepten-3-one; 13) 1-(4-Hydroxy-3-indolylphenyl)-7-(4-hydroxy-3, 5-dimethoxyoxyphenyl)-4-hepten-3-one;

14) 1-(4-Hydroxy-3,5-dimethoxyphenyl)-7-(4-hydroxy-3-indolylphenyl)-4-hepten-3-one;

15) 1-(4-Hydroxy-3-indolylphenyl)-7-(4-hydroxyphenyl)-4-hepten-3-one;

16) 1,7-diphenyl-3,5-heptanedione;

17) 1-(4-Hydroxy-3-indolylphenyl)-7-phenyl-3,5-heptanedione.

A pharmaceutical composition comprising the diphenylheptanone compound according to claim 1 as an active ingredient, characterized in that the pharmaceutical composition comprises 0.1% by weight to 9% by weight and according to claim 1 compound of.

4. A pharmaceutical composition according to claim 2, characterized in that the pharmaceutical composition comprises from 0.5% to 10% by weight of the compound of claim 1.

The pharmaceutical composition according to claim 2 or 3, which is for use in the preparation of a medicament for treating gastrointestinal diseases.

Use of a pharmaceutical composition according to claim 4, characterized in that the pharmaceutical composition is useful for the prevention and treatment of gastrointestinal ulcer diseases caused by H. pylori.