Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C233/00—Carboxylic acid amides
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

• This invention relates to oxaminic acids and esters thereof, a process for the preparation of said compounds and pharmaceutical compositions containing these compounds.
• R 1 is alkyl of 1 to 10 carbon atoms, this preferably contains 1 to 5 carbon atoms, especially 2 or 3 carbon atoms.
• R 1 can also be hydrogen.
• R 2 can be chlorine.
• R 2 can also be alkoxy of 1 to 4 carbon atoms.
• R 1 and R 2 together can also be -(CH 2 ) m - wherein m is 3 or 4, preferably 3.
• R 3 can be OH.
• R 3 can also be alkoxy of 1 to 4 carbon atoms.
• the invention also provides a process for the production of compounds of formula I comprising,
• Process variant a) can be effected according to known methods.
• the reaction- may conveniently be effected in the presence of an inert solvent such as a hydrocarbon, chlorinated hydrocarbon, an ether or a tertiary amine, or in an excess of the compound of formula III.
• the reaction may suitably be effected at a temperature of from -5° to 200°C.
• a basic catalyst such as a tertiary amine, for example pyridine or triethylamine may be employed.
• R 4 is alkoxy of 1 to 4 carbon atoms, this preferably has the same significance as R 3 .
• Process variant b) can be effected according to known methods.
• the reaction is preferably effected in the presence of a base, for example in the presence of a dilute alkali metal hydroxide or a tertiary amine.
• the reaction may suitably be effected at a temperature of from O°C to the boiling temperature of the reaction mixture, conveniently in the presence of an inert organic solvent which is miscible with water, such as a lower alcohol, dimethyl sulphoxide or dimethoxy ethane.
• the resulting compounds of formula I may be isolated and purified using conventional techniques.
• the compounds of formula I wherein R 3 is OH may be converted into salt forms in conventional manner and vice versa.
• Suitable salt forms include those with alkali metals, for example sodium and potasium, alkaline earth metals, for example calcium and magnesium, and with organic bases such as amines.
• the compounds of formula II can be prepared by nitrating a compound of formula IV, 0 for example in a mixture of sulphuric and nitric acids, and reducing the resulting nitro derivative, according to known methods, to yield the compounds of formula II.
• the reduction may conveniently be effected by catalytic hydrogenation or by using iron filings in an aqueous acid.
• the 2,6,7,8,9,9a-hexahydro-2-oxo-1H-benz[c,d]-azulen-3yl-amine employed as starting material can be prepared as follows:
• a solution of 0.95 g of potassium hydroxide in 2 ml of water is added to a solution of 4 g of the title compound of Example 1 in 150 ml of methanol and the mixture refluxed for 1 hour.
• the solution is concentrated, diluted with water and the neutral side products extracted with CH 2 Cl 2 .
• the aqueous phase is acidified with hydrochloric acid and the title compound filtered off. M.P. 191-192°.
• the compounds of formula I exhibit pharmacological activity.
• the compounds exhibit disodium chromoglycate (DSCG)-like activity, in particular histamine release inhibiting activity, and are therefore indicated for use in the treatment and prophylaxis of allergic conditions, such as allergic asthma, exercise induced asthma and allergic gastrointestinal disorders, as indicated in the passive cutaneous anaphylaxis (PCA) test in the rat, based on the principles of Mota, J. Immunology, (1964);7, 681.
• DSCG disodium chromoglycate
• the (DSCG)-like activity in particular histamine release inhibiting activity, can be confirmed by inhibition of histamine release in the rat peritoneal mast cell test, basically as described by Kusner et al., J. Pharmacol. Exp. Therap. (1973), 184, 41-46.
• An indicated suitable daily dosage is from about 1 to about 100 mg, suitably administered in divided doses of from about 0.25 to about 50 mg, 2 to 4 times daily or in retard form.
• the compounds of formula I wherein R 3 is OH may be administered in free form or in pharmaceutically acceptable salt form.
• Such salt forms possess the same order of activity as the free forms and are readily prepared in conventional manner. Examples of suitable salt forms are those of sodium and potassium.
• the invention also provides a pharmaceutical composition
• a pharmaceutical composition comprising a compound of formula I, and in the case of compounds wherein R 3 is OH, in free form or in pharmaceutically acceptable salt form, in association with a pharmaceutically acceptable diluent or carrier.
• Such compositions may, for example, be in the form of a solution or capsule.

Landscapes

• Organic Chemistry (AREA)
• Chemical & Material Sciences (AREA)
• Health & Medical Sciences (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Life Sciences & Earth Sciences (AREA)
• Chemical Kinetics & Catalysis (AREA)
• General Chemical & Material Sciences (AREA)
• Medicinal Chemistry (AREA)
• Engineering & Computer Science (AREA)
• Pharmacology & Pharmacy (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
• Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Applications Claiming Priority (4)

Publications (2)

Family

ID=25702447

Family Applications (1)

Country Status (14)

Cited By (1)

Families Citing this family (3)

Citations (1)

Family Cites Families (7)

• 1978
  • 1978-06-15 DE DE7878100167T patent/DE2861051D1/de not_active Expired
  • 1978-06-15 EP EP78100167A patent/EP0000152B1/de not_active Expired
  • 1978-06-19 FI FI781946A patent/FI781946A/fi not_active Application Discontinuation
  • 1978-06-19 DK DK275378A patent/DK275378A/da not_active Application Discontinuation
  • 1978-06-22 US US05/917,949 patent/US4148916A/en not_active Expired - Lifetime
  • 1978-06-26 PT PT68216A patent/PT68216A/pt unknown
  • 1978-06-26 IL IL55006A patent/IL55006A/xx unknown
  • 1978-06-26 NZ NZ187677A patent/NZ187677A/xx unknown
  • 1978-06-26 AU AU37469/78A patent/AU519473B2/en not_active Expired
  • 1978-06-26 PH PH21307A patent/PH14995A/en unknown
  • 1978-06-26 IE IE1272/78A patent/IE47627B1/en unknown
  • 1978-06-27 IT IT25028/78A patent/IT1097293B/it active
  • 1978-06-27 JP JP7708478A patent/JPS5412360A/ja active Pending
  • 1978-06-27 CA CA306,275A patent/CA1130307A/en not_active Expired

Patent Citations (1)

Also Published As

Similar Documents

Legal Events