US4377591A
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7-Oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid derivatives, their use and preparation
Assignee: Sankyo Co Ltd
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Filing: 1981-02-27
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Granted: 1983-03-22
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Expires: 2001-02-27
Abstract
Abstract 7-Oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid derivatives of formula (I): ##STR1## (in which:) R 1 represents a hydrogen atom or an optionally substituted alkyl group; X represents an oxy group, a thio group, a sulphinyl group or a sulphonyl group; A represents a bivalent for trivalent saturated aliphatic hydrocarbon group; p is 1 (when A is bivalent) or 2 (when A is trivalent); R 2 represents an azido, nitro or cyano group or one of the groups of formula ##STR2## m and n are the same or different and each is 0 or 1; R represents an amidino group or a group of formula R 4 , --N(R 4 ) 2 or --YR 4 , B represents a group of formula ##STR3## D represents a group of formula ##STR4## (provided that, where m and n are both 1, the groups represented by B and D must be different); R 4 represents a hydrogen atom or an alkyl group and, where there are 2 or more groups represented by R 4 , they may be the same or different, and Y represents an oxygen atom or a sulphur atom; and R 3 represents a carboxy group or a protected carboxy group) and pharmaceutically acceptable salts thereof are valuable antibiotics and may be prepared by a process which includes heating a corresponding phosphorus-ylide compound.
Inventors
- 👤 Tetsuo Hiraoka
- 👤 Takeo Kobayashi
- 👤 Noboru Ishida
- 👤 Shinichi Sugawara
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-05 08:07
CPC Classifications
C; C07; C07D; C07D477/00; C07D477/10; C07D477/12; C07D477/14; A; A61; A61P; A61P31/00; A61P31/04; C07D205/00; C07D205/02; C07D205/06; C07D205/08; C07F; C07F7/00; C07F7/02; C07F7/08; C07F7/10; C07F7/18; C07F7/1804; C07F9/00; C07F9/02; C07F9/547; C07F9/553; C07F9/568; Y; Y02; Y02P; Y02P20/00; Y02P20/50; Y02P20/55
Claims Analysis
Total Claims: 15
Claim 1
Independent Claim
52 words
Compounds selected from the group consisting of: 3-(2-aminoethylthiomethyl)-6-(1-hydroxyethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid; 3-(2-formimidoylaminoethylthiomethyl)-6-(1-hydroxyethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid; 3-(2-amino-1-methylethyl)thiomethyl-6-(1-hydroxyethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid; 3-(2-formimidoylamino-1-methylethyl)thiomethyl-6-(1-hydroxyethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid; 3-(3-aminopropylthiomethyl)-6-(1-hydroxyethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid; 3-(3-formimidoylaminopropylthiomethyl)-6-(1-hydroxyethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid; 3-(2-aminoethylsulphinylmethyl)-6-(1-hydroxyethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid; 3-(2-formimidoylaminoethylsulphinylmethyl)-6-(1-hydroxyethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid; 3-(2-amino-1-methylethyl)sulphinylmethyl-6-(1-hydroxyethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid; 3-(2-formimidoylamino-1-methylethyl)sulphinylmethyl-6-(1-hydroxyethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid; 3-(2-aminoethylsulphonylmethyl)-6-(1-hydroxyethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid; 3-(2-formimidoylaminoethylsulphonylmethyl)-6-(1-hydroxyethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid; 3-(2-amino-1-methylethyl)sulphonylmethyl-6-(1-hydroxyethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid; 3-(2-formimidoylamino-1-methylethyl)sulphonylmethyl-6-(1-hydroxyethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid; pivaloyloxymethyl 3-(2-aminoethylthiomethyl)-6-(1-hydroxyethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate; pivaloyloxymethyl 3-(2-formimidoylaminoethylthiomethyl)-6-(1-hydroxyethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate; pivaloyloxymethyl 3-(2-amino-1-methylethyl)thiomethyl-6-(1-hydroxyethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate; and pivaloyloxymethyl 3-(2-formimidoylamino-1-methylethyl)thiomethyl-6-(1-hydroxyethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate; and pharmaceutically accepted salts of said carboxylic acids.
Claim 2
Dependent Claim
52 words
Compounds selected from the group consisting of: 3-(2-aminoethylthiomethyl)-6-(1-hydroxyethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid; 3-(2-formimidoylaminoethylthiomethyl)-6-(1-hydroxyethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid; 3-(2-amino-1-methylethyl)thiomethyl-6-(1-hydroxyethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid; 3-(2-formimidoylamino-1-methylethyl)thiomethyl-6-(1-hydroxyethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid; 3-(3-aminopropylthiomethyl)-6-(1-hydroxyethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid; 3-(3-formimidoylaminopropylthiomethyl)-6-(1-hydroxyethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid; 3-(2-aminoethylsulphinylmethyl)-6-(1-hydroxyethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid; 3-(2-formimidoylaminoethylsulphinylmethyl)-6-(1-hydroxyethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid; 3-(2-amino-1-methylethyl)sulphinylmethyl-6-(1-hydroxyethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid; 3-(2-formimidoylamino-1-methylethyl)sulphinylmethyl-6-(1-hydroxyethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid; 3-(2-aminoethylsulphonylmethyl)-6-(1-hydroxyethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid; 3-(2-formimidoylaminoethylsulphonylmethyl)-6-(1-hydroxyethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid; 3-(2-amino-1-methylethyl)sulphonylmethyl-6-(1-hydroxyethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid; 3-(2-formimidoylamino-1-methylethyl)sulphonylmethyl-6-(1-hydroxyethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid; pivaloyloxymethyl 3-(2-aminoethylthiomethyl)-6-(1-hydroxyethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate; pivaloyloxymethyl 3-(2-formimidoylaminoethylthiomethyl)-6-(1-hydroxyethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate; pivaloyloxymethyl 3-(2-amino-1-methylethyl)thiomethyl-6-(1-hydroxyethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate; and pivaloyloxymethyl 3-(2-formimidoylamino-1-methylethyl)thiomethyl-6-(1-hydroxyethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate; and pharmaceutically accepted salts of said carboxylic acids.
Claim 3
Dependent Claim
14 words
The compounds of claim 1 which are 3-(2-aminoethylthiomethyl)-6-(1-hydroxyethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid and pharmaceutically acceptable salts thereof.
Claim 4
Dependent Claim
10 words
The compound of claim 1 which is the pivaloyloxymethyl 3-(2-aminoethylthiomethyl)-6-(1-hydroxyethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate.
Claim 5
Dependent Claim
14 words
The compounds of claim 1 which are 3-(2-formimidoylaminoethylthiomethyl)-6-(1-hydroxyethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid and pharmaceutically acceptable salts thereof.
Claim 6
Dependent Claim
10 words
The compound of claim 1 which is the pivaloyloxymethyl 3-(2-formimidoylaminoethylthiomethyl)-6-(1-hydroxyethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate.
Claim 7
Dependent Claim
14 words
The compounds of claim 1 which are 3-(2-amino-1-methylethyl)thiomethyl-6-(1-hydroxyethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid and pharmaceutically acceptable salts thereof.
Claim 8
Dependent Claim
10 words
The compound of claim 1 which is the pivaloyloxymethyl 3-(2-amino-1-methylethyl)thiomethyl-6-(1-hydroxyethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate.
Claim 9
Dependent Claim
14 words
The compounds of claim 1 which are 3-(2-formimidoylamino-1-methylethyl)thiomethyl-6-(1-hydroxyethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid and pharmaceutically acceptable salts thereof.
Claim 10
Dependent Claim
10 words
The compound of claim 1, which is the pivaloyloxymethyl 3-(2-formimidoylamino-1-methylethyl)thiomethyl-6-(1-hydroxyethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate.
Claim 11
Dependent Claim
26 words
The compounds of any one of claims 1, 2, 3, 4, 5, 6, 7, 8, or 9 wherein said compounds are in the (5R, 6S) configuration.
Claim 12
Dependent Claim
26 words
The compounds of any one of claims 1, 2, 3, 4, 5, 6, 7, 8, or 9 wherein said compounds are in the (5R, 6R) configuration.
Claim 13
Dependent Claim
10 words
The compound of claim 1 which is (5R, 6S)-3-(2-aminoethylthiomethyl)-6-[1-(R)-hydroxyethyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid.
Claim 14
Dependent Claim
35 words
A pharmaceutical composition comprising an antibiotically effective amount of at least one compound of any one of claims 1, 2, 3, 4, 5, 6, 7, 8, 9, or 12 together with a pharmaceutically acceptable carrier.
Claim 15
Dependent Claim
19 words
The composition of claim 13 wherein said antibiotic is selected from: (5R, 6S)-3-(2-aminoethylthiomethyl)-6-[1-(R)-hydroxyethyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid and pharmaceutically acceptable salts thereof.
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1986-03-21 | 1986-09-20 | 1987-03-22 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1990-03-21 | 1990-09-20 | 1991-03-22 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1994-03-21 | 1994-09-20 | 1995-03-22 | $7700.00 | Window Closed / Lapsed |