EP0000152B1 - Oxaminic acids and esters, process for their preparation and pharmaceutical compositions containing them - Google Patents

Oxaminic acids and esters, process for their preparation and pharmaceutical compositions containing them Download PDF

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Publication number
EP0000152B1
EP0000152B1 EP78100167A EP78100167A EP0000152B1 EP 0000152 B1 EP0000152 B1 EP 0000152B1 EP 78100167 A EP78100167 A EP 78100167A EP 78100167 A EP78100167 A EP 78100167A EP 0000152 B1 EP0000152 B1 EP 0000152B1
Authority
EP
European Patent Office
Prior art keywords
compound
carbon atoms
formula
alkoxy
compounds
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired
Application number
EP78100167A
Other languages
German (de)
English (en)
French (fr)
Other versions
EP0000152A1 (en
Inventor
Trevor Glyn Dr. Payne
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Sandoz AG
Original Assignee
Sandoz AG
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Sandoz AG filed Critical Sandoz AG
Publication of EP0000152A1 publication Critical patent/EP0000152A1/en
Application granted granted Critical
Publication of EP0000152B1 publication Critical patent/EP0000152B1/en
Expired legal-status Critical Current

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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 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 0°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, 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-1 H-benz[c,d]azulen-3yl-amine employed as starting material can be prepared as follows:
  • 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
  • PCA passive cutaneous anaphylaxis
  • 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 1 to 100 mg, suitably administered in divided doses of from 0.25 to 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

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (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)
EP78100167A 1977-06-28 1978-06-15 Oxaminic acids and esters, process for their preparation and pharmaceutical compositions containing them Expired EP0000152B1 (en)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
CH791377 1977-06-28
CH7914/77 1977-06-28
CH791477 1977-06-28
CH7913/77 1977-06-28

Publications (2)

Publication Number Publication Date
EP0000152A1 EP0000152A1 (en) 1979-01-10
EP0000152B1 true EP0000152B1 (en) 1981-09-09

Family

ID=25702447

Family Applications (1)

Application Number Title Priority Date Filing Date
EP78100167A Expired EP0000152B1 (en) 1977-06-28 1978-06-15 Oxaminic acids and esters, process for their preparation and pharmaceutical compositions containing them

Country Status (14)

Country Link
US (1) US4148916A (it)
EP (1) EP0000152B1 (it)
JP (1) JPS5412360A (it)
AU (1) AU519473B2 (it)
CA (1) CA1130307A (it)
DE (1) DE2861051D1 (it)
DK (1) DK275378A (it)
FI (1) FI781946A (it)
IE (1) IE47627B1 (it)
IL (1) IL55006A (it)
IT (1) IT1097293B (it)
NZ (1) NZ187677A (it)
PH (1) PH14995A (it)
PT (1) PT68216A (it)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ATE1606T1 (de) * 1978-12-22 1982-10-15 Sandoz Ag Indanyloxaminsaeure-derivate, ihre herstellung und diese enthaltende pharmazeutische zusammensetzungen.
DE2926271A1 (de) * 1979-06-29 1981-01-08 Behringwerke Ag Mittel zum nachweis peroxidatisch wirksamer substanzen
US4290773A (en) * 1979-11-13 1981-09-22 Miles Laboratories, Inc. Stabilization of benzidine-type indicators with various enhancers
US4579869A (en) * 1985-08-02 1986-04-01 Merck & Co., Inc. Substituted [(2,3-dihydro-1-oxo-1H-inden-5-yl)amino]alkanoic acids, their derivatives and their salts

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2589934A (en) * 1950-08-24 1952-03-18 Abbott Lab 2-aminomethyl-tetrahydroacenapthones-1 and their preparation
CH485485A (de) * 1966-02-07 1970-02-15 Ciba Geigy Verwendung von Oxalsäure-esteramiden als Ultraviolettschutzmittel ausserhalb der Textilindustrie
US3993679A (en) * 1972-12-20 1976-11-23 The Upjohn Company Cyano phenylene dioxamic molecules
US4069343A (en) * 1973-03-23 1978-01-17 American Home Products Corporation Oxamic acid derivatives for the prevention of immediate type hypersensitivity reactions
US3966965A (en) * 1973-03-23 1976-06-29 American Home Products Corporation Oxamic acid derivatives for the prevention of immediate type hypersensitivity reactions
US4011337A (en) * 1975-07-07 1977-03-08 The Upjohn Company Oxamide-oxamic compounds, compositions and methods of use
US4017538A (en) * 1975-10-01 1977-04-12 The Upjohn Company Alkyl thio sulfinyl and sulfonyl oxamic compounds, compositions and methods of use
US4061791A (en) * 1975-12-29 1977-12-06 The Upjohn Company Anti-allergic oxanilate compounds

Also Published As

Publication number Publication date
FI781946A (fi) 1978-12-29
IT7825028A0 (it) 1978-06-27
IE781272L (en) 1978-12-28
IT1097293B (it) 1985-08-31
JPS5412360A (en) 1979-01-30
PH14995A (en) 1982-03-22
US4148916A (en) 1979-04-10
NZ187677A (en) 1981-01-23
IE47627B1 (en) 1984-05-16
EP0000152A1 (en) 1979-01-10
AU3746978A (en) 1980-01-03
DK275378A (da) 1978-12-29
AU519473B2 (en) 1981-12-03
CA1130307A (en) 1982-08-24
PT68216A (fr) 1978-07-01
IL55006A (en) 1981-11-30
IL55006A0 (en) 1978-08-31
DE2861051D1 (en) 1981-11-26

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