US4322345A
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2-Azetidinone 4-carboxy derivatives and a process for producing the same
Assignee: KH Neochem Co Ltd
•
Filing: 1980-04-21
•
Granted: 1982-03-30
•
Expires: 2000-04-21
Abstract
Abstract A 2-azetidinone of formula (I): <IMAGE> (I) wherein R1 represents an aralkoxy, acyloxy, sulphonyloxy or amino group any of which may be substituted, or hydrogen, hydroxy, alkoxy or azido; R2 represents an alkyl or aralkyl group either of which may be substituted, or hydrogen; R3 represents an alkyl, aryl, aralkyl, alkenyl, aralkenyl, alkynyl, aralkynyl, acyl or heterocyclic group any of groups may be substituted; and R4 represents an alkyl, alkenyl, aryl or aralkyl group any of which may be substituted; or formula (I'): <IMAGE> (I') wherein R1' is the same as R1 above; R2' represents an alkyl, aralkyl or trialkylsilyl group any of which may be substituted, or hydrogen; R3' is the same as R3 above; and R4' represents an alkyl, aralkyl or trialkylsilyl group any of which may be substituted, or hydrogen; provided that when R1' represents azido or optionally substituted amino, R2' represents hydrogen or CH2CCl3 and R4' represents <IMAGE> R3' represents other than <IMAGE> or a pharmaceutically acceptable salt thereof is disclosed. The derivatives exhibit beta -lactamase inhibiting activity and are thus of interest as anti-bacterial agents, used alone or together with known antibiotic subtances.
Inventors
- 👤 Tadashi Hirata
- 👤 Akira Sato
- 👤 Nobuhiro Nakamizo
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-02 11:52
CPC Classifications
C; C07; C07D; C07D205/00; C07D205/02; C07D205/06; C07D205/08
Claims Analysis
Total Claims: 40
Claim 1
Independent Claim
518 words
A 2-azetidinone derivative selected from the group consisting of compounds of formulae (Ia) and (I'a) as follows, and their pharmaceutically acceptable salts: ##STR43## wherein: R 1 is selected from the group consisting of aralkoxy, C 1 5 alkanoyloxy, methanesulphonyloxy and p-toluenesulphonyloxy, any one of which groups may be mono-substituted with halogen, C 1 to C 5 alkyl, C 1 to C 5 alkoxy and nitro group; hydrogen, hydroxy, and C 1 to C 5 alkoxy group; R 2 is selected from the group consisting of C 1 to C 5 alkyl and aralkyl, either of which groups may be mono-substituted with halogen, C 1 to C 5 alkyl, C 1 to C 5 alkoxy and nitro group; and hydrogen; R 3 is selected from the group consisting of C 1 to C 5 alkyl, phenyl, naphtyl, aralkyl, C 2 to C 5 alkynyl, aralkynyl, C 2 to C 5 alkynyl, aralkynyl and acetyl, propionyl, and butyryl, and of which groupds may be mono-substituted with halogen, C 1 to C 5 , alkyl, C 1 to C 5 alkoxy, C 1 5 alkanoyloxy, hydroxy, amino, phthalylimino, carbobenzoxyamino benzylamino and nitro group; 2- or 3-furyl, 5-methyl-2-furyl, 2- or 3-thienyl, 2- or 3-pyrrolyl, 2- or 4-imidazolyl, 3-pyrazolyl, 4-isoxazolyl, 2-, 3-, 4-, 5-, 6- or 7-indolyl or 2- or 3-benzo(b) furanyl; and R 4 is selected from the group consisting of C 1 to C 5 alkyl, C 2 to C 5 alkenyl, phenyl, naphthyl and aralkyl, any one of which groups may be mono-substituted with halogen, C 1 to C 5 alkyl, C 1 to C 5 alkoxy, C 1 5 alkanoyloxy, hydroxy, amino, phthalylimino, carbobenzoxyamino, benzylamino, and nitro group, ##STR44## wherein: R' 1 is selected from the group consisting of aralkoxy, C 1 5 alkanoyloxy, methanesulphonyloxy and p-toluene-sulphonyloxy, any one of which groups may be mono-substituted with halogen, C 1 to C 5 alkyl, C 1 to C 5 alkoxy, and nitro; hydrogen, hydroxy, and C 1 to C 5 alkoxy group; R' 2 is selected from the group consisting of C 1 to C 5 alkyl, aralkyl and t-butyl dimethylsilyl and trimethylsilyl, and one of which groups may be mono-substituted with halogen, C 1 to C 5 alkyl, C 1 to C 5 alkoxy and nitro group; and hydrogen; R' 3 is selected from the group consisting of C 1 to C 5 alkyl, phenyl, naphthyl, aralkyl, C 2 to C 5 alkenyl, aralkynyl, C 2 to C 5 alkynyl, aralkenyl, acetyl, propionyl and butyryl, any one of which groups may be mono-substituted with halogen, C 1 to C 5 alkyl, C 1 to C 5 alkoxy, C 1 5 alkanoyloxy, hydroxy, amino, phthalylimino, carbobenzoxyamino, benzylamino, and nitro group, 2- or 3-furyl, 2- or 3-thienyl, 2- or 3-pyrrolyl, 2- or 4-imidazolyl, 3-pyrazolyl, 4-isoxazolyl, 2-, 3-, 4-, 5-, 6- or 7-indolyl or 2- or 3-benzo(b)furanyl; and R' 4 selected from the group consisting of C 1 to C 5 alkyl, arallkyl and trialkylsilyl, any one of which groups may be mono-substituted with halogen, C 1 to C 5 alkyl, C 1 to C 5 alkoxy and nitro group, and hydrogen.
Claim 2
Dependent Claim
518 words
A 2-azetidinone derivative selected from the group consisting of compounds of formulae (Ia) and (I'a) as follows, and their pharmaceutically acceptable salts: ##STR43## wherein: R 1 is selected from the group consisting of aralkoxy, C 1 5 alkanoyloxy, methanesulphonyloxy and p-toluenesulphonyloxy, any one of which groups may be mono-substituted with halogen, C 1 to C 5 alkyl, C 1 to C 5 alkoxy and nitro group; hydrogen, hydroxy, and C 1 to C 5 alkoxy group; R 2 is selected from the group consisting of C 1 to C 5 alkyl and aralkyl, either of which groups may be mono-substituted with halogen, C 1 to C 5 alkyl, C 1 to C 5 alkoxy and nitro group; and hydrogen; R 3 is selected from the group consisting of C 1 to C 5 alkyl, phenyl, naphtyl, aralkyl, C 2 to C 5 alkynyl, aralkynyl, C 2 to C 5 alkynyl, aralkynyl and acetyl, propionyl, and butyryl, and of which groupds may be mono-substituted with halogen, C 1 to C 5 , alkyl, C 1 to C 5 alkoxy, C 1 5 alkanoyloxy, hydroxy, amino, phthalylimino, carbobenzoxyamino benzylamino and nitro group; 2- or 3-furyl, 5-methyl-2-furyl, 2- or 3-thienyl, 2- or 3-pyrrolyl, 2- or 4-imidazolyl, 3-pyrazolyl, 4-isoxazolyl, 2-, 3-, 4-, 5-, 6- or 7-indolyl or 2- or 3-benzo(b) furanyl; and R 4 is selected from the group consisting of C 1 to C 5 alkyl, C 2 to C 5 alkenyl, phenyl, naphthyl and aralkyl, any one of which groups may be mono-substituted with halogen, C 1 to C 5 alkyl, C 1 to C 5 alkoxy, C 1 5 alkanoyloxy, hydroxy, amino, phthalylimino, carbobenzoxyamino, benzylamino, and nitro group, ##STR44## wherein: R' 1 is selected from the group consisting of aralkoxy, C 1 5 alkanoyloxy, methanesulphonyloxy and p-toluene-sulphonyloxy, any one of which groups may be mono-substituted with halogen, C 1 to C 5 alkyl, C 1 to C 5 alkoxy, and nitro; hydrogen, hydroxy, and C 1 to C 5 alkoxy group; R' 2 is selected from the group consisting of C 1 to C 5 alkyl, aralkyl and t-butyl dimethylsilyl and trimethylsilyl, and one of which groups may be mono-substituted with halogen, C 1 to C 5 alkyl, C 1 to C 5 alkoxy and nitro group; and hydrogen; R' 3 is selected from the group consisting of C 1 to C 5 alkyl, phenyl, naphthyl, aralkyl, C 2 to C 5 alkenyl, aralkynyl, C 2 to C 5 alkynyl, aralkenyl, acetyl, propionyl and butyryl, any one of which groups may be mono-substituted with halogen, C 1 to C 5 alkyl, C 1 to C 5 alkoxy, C 1 5 alkanoyloxy, hydroxy, amino, phthalylimino, carbobenzoxyamino, benzylamino, and nitro group, 2- or 3-furyl, 2- or 3-thienyl, 2- or 3-pyrrolyl, 2- or 4-imidazolyl, 3-pyrazolyl, 4-isoxazolyl, 2-, 3-, 4-, 5-, 6- or 7-indolyl or 2- or 3-benzo(b)furanyl; and R' 4 selected from the group consisting of C 1 to C 5 alkyl, arallkyl and trialkylsilyl, any one of which groups may be mono-substituted with halogen, C 1 to C 5 alkyl, C 1 to C 5 alkoxy and nitro group, and hydrogen.
Claim 3
Dependent Claim
260 words
The compound of formula (Ia) of claim 1 wherein: R 1 is selected from the group consisting of benzyloxy, C 1 5 alkanoyloxy, p-toluenesulphyonyloxy and methanesulphonyloxy, any one of which groups may be monosubstituted with halogen, C 1 to C 5 alkyl, C 1 to C 5 alkoxy and nitro group; hydrogen, hydroxy and t-butoxy group; R 2 is selected from the group consisting of C 1 to C 5 alkyl benzyl and diphenylmethyl, any of which groups may be mono-substituted with halogen, C 1 to C 5 alkyl, C 1 to C 5 alkoxy and nitro group; and hydrogen; R 3 is selected from the group consisting of C 1 to C 5 alkyl, phenyl, naphthyl, benzyl, C 2 to C 5 alkenyl, styryl, cinnamyl, C 2 to C 5 alkynyl, 2-phenyl-1-ethynyl, acetyl, propionyl and butyryl, any one of which groups may be mono-substituted with halogen, C 1 to C 5 alkyl, C 1 to C 5 alkoxy, C 1 5 alkanoyloxy, hydroxy, amino, phthylimino, carbobenzoxyamino, benzylamino and nitro group; 2- or 3-furyl, 5-methyl-2-furyl, 2- or 3-thienyl, 2- or 3-pyrrolyl, 2- or 4-imidazolyl, 3-pyrazolyl, 4-isoxazolyl, 2-, 3-, 4-, 5-, 6- or 7-indolyl or 2- or 3-benzo(b)furanyl; and R 4 is selected from the group consisting of C 1 to C 5 alkyl, C 2 to C 5 alkenyl, phenyl, naphthyl, benzyl, diphenylmethyl, trityl and phthalidyl, and one of which groups may be monosubstituted with halogen, C 1 to C 5 alkyl, C 1 to C 5 alkoxy, C 1 5 alkanoyloxy, hydroxy, amino, phthalylimino, carbobenzoxyamino, benzylamino and nitro group.
Claim 4
Dependent Claim
65 words
The compound of claim 2, wherein R 1 is selected from the group consisting of hydrogen and t-butoxy group; R 2 is selected from the group consisting of methyl, t-butyl and benzyl group; R 3 is selected from the group consisting of i-propyl, phenyl, 3-methoxyphenyl, styryl, acetyl and 5-methyl-2-furyl group; and R 4 is selected from the group consisting of ethyl, t-butyl and phenyl group.
Claim 5
Dependent Claim
254 words
The compound of formula (I'a) of claim 1 wherein; R 1 ' is selected from the group consisting of benzyloxy, C 1 5 alkanoyloxy, p-toluenesulphonyloxy, and methanesulphonyloxy, any one of which groups may be monosubstituted with halogen, C 1 to C 5 alkyl, C 1 to C 5 alkoxy and nitro group; benzylamino, hydrogen, hydroxy and t-butoxy; R 2 ' is selected from the group consisting of C 1 to C 5 alkyl, benzyl, diphenylmethyl, trityl, phthalidyl and t-butyldimethylsilyl and trimethylsilyl, any one of which groups may be substituted with halogen, C 1 to C 5 alkyl, C 1 to C 5 alkoxy and nitro group; and hydrogen; R 3 ' is selected from the group consisting of C 1 to C 5 alkyl, phenyl, naphthyl, benzyl, C 2 to C 5 alkenyl, styryl, cinnamyl, C 2 to C 5 alkynyl, 2-phenyl-1-ethynyl, acetyl, propionyl, butyryl, 2- or 3-furyl, 2- or 3-thienyl, 2- or 3-pyrrolyl, 2- or 4-imidazolyl, 3-pyrazolyl, 4-isoxazolyl, 2-, 3-, 4-, 5-, 6- or 7-indolyl 5-methyl-2-furyl and 2- or 3-benzy(b)furanyl, any of which groups may be mono-substituted with halogen, C 1 to C 5 alkyl, C 1 to C 5 alkoxy, C 1 5 alkanoyloxy, amino, phthalylimino, carbobenzoxyamino, benzylamino and nitro group; and R 4 ' is selected from the group consisting of C 1 to C 5 alkyl, benzyl, diphenylmethyl, trityl, phthalidyl, and t-butyldimethylsilyl and trimethylsilyl, and of which groups may be mono-substituted with halogen C 1 to C 5 alkyl, C 1 to C 5 alkoxy and nitro group; and hydrogen.
Claim 6
Dependent Claim
47 words
The compound of claim 4, wherein R 1 ' is hydrogen; R 2 ' is selected from the group consisting of benzyl group and hydrogen; R 3 ' is selected from the group consisting of phenyl, 3-methoxyphenyl and 5-methyl-2-furyl group; and R 4 ' is methyl group.
Claim 7
Dependent Claim
2 words
(4S)-t-butyl-α-(4-benzyloxycarbonyl-2-oxoazetidine-1-yl)-α-(acetyl) acetaminde.
Claim 8
Dependent Claim
2 words
(4S)-t-butyl-α-(4-benzyloxycarbonyl-2-oxoazetidine-1-yl)-α-(acetyl) acetaminde.
Claim 9
Dependent Claim
2 words
(4S)-t-butyl-α-(4-methoxycarbonyl-2-oxoazetidine-1-yl)-α-(styryl) acetamide.
Claim 10
Dependent Claim
2 words
(4S)-t-butyl-α-(4-methoxycarbonyl-2-oxoazetidine-1-yl)-α-(styryl) acetamide.
Claim 11
Dependent Claim
2 words
(4S)-t-butyl-α-(4-methoxycarbonyl-2-oxoazetidine-1-yl)-α-(isopropyl) acetamide.
Claim 12
Dependent Claim
2 words
(4S)-t-butyl-α-(4-methoxycarbonyl-2-oxoazetidine-1-yl)-α-(isopropyl) acetamide.
Claim 13
Dependent Claim
2 words
(4S)-t-butyl-α-(4-benzyloxycarbonyl-2-oxoazetidine-1-yl)-α-(phenyl) acetamide.
Claim 14
Dependent Claim
2 words
(4S)-t-butyl-α-(4-benzyloxycarbonyl-2-oxoazetidine-1-yl)-α-(phenyl) acetamide.
Claim 15
Dependent Claim
2 words
(4S)-ethyl-α-(4-methoxycarbonyl-2-oxoazetidine-1-yl)-α-(acetyl) acetamide.
Claim 16
Dependent Claim
2 words
(4S)-ethyl-α-(4-methoxycarbonyl-2-oxoazetidine-1-yl)-α-(acetyl) acetamide.
Claim 17
Dependent Claim
2 words
(4S)-ethyl-α-(4-benzyloxycarbonyl-2-oxoazetidine-1-yl)-α-(acetyl) acetamide.
Claim 18
Dependent Claim
2 words
(4S)-ethyl-α-(4-benzyloxycarbonyl-2-oxoazetidine-1-yl)-α-(acetyl) acetamide.
Claim 19
Dependent Claim
2 words
3,4-erythro-ethyl-α-(4-t-butoxycarbonyl-3-t-butoxy-2-oxoazetidine-1-yl)-α-(acetyl) acetamide.
Claim 20
Dependent Claim
2 words
3,4-erythro-ethyl-α-(4-t-butoxycarbonyl-3-t-butoxy-2-oxoazetidine-1-yl)-α-(acetyl) acetamide.
Claim 21
Dependent Claim
2 words
(4S)-ethyl-α-(4-methoxycarbonyl-2-oxoazetidine-1-yl)-α-(phenyl) acetamide.
Claim 22
Dependent Claim
2 words
(4S)-ethyl-α-(4-methoxycarbonyl-2-oxoazetidine-1-yl)-α-(phenyl) acetamide.
Claim 23
Dependent Claim
2 words
(4S)-phenyl-α-(4-benzyloxycarbonyl-2-oxoazetidine-1-yl)-α-(phenyl) acetamide.
Claim 24
Dependent Claim
2 words
(4S)-phenyl-α-(4-benzyloxycarbonyl-2-oxoazetidine-1-yl)-α-(phenyl) acetamide.
Claim 25
Dependent Claim
2 words
(4S)-phenyl-α-(4-benzyloxycarbonyl-2-oxoazetidine-1-yl)-α-(3-methoxyphenol) acetamide.
Claim 26
Dependent Claim
2 words
(4S)-phenyl-α-(4-benzyloxycarbonyl-2-oxoazetidine-1-yl)-α-(3-methoxyphenol) acetamide.
Claim 27
Dependent Claim
2 words
(4S)-phenyl-α-(4-benzyloxycarbonyl-2-oxoazetidine-1-yl)-α-(5-methylfuran-2-yl) acetamide.
Claim 28
Dependent Claim
2 words
(4S)-phenyl-α-(4-benzyloxycarbonyl-2-oxoazetidine-1-yl)-α-(5-methylfuran-2-yl) acetamide.
Claim 29
Dependent Claim
2 words
(4S)-methyl-α-(4-benzyloxycarbonyl-2-oxoazetidine-1-yl)-α-(phenyl) acetate.
Claim 30
Dependent Claim
2 words
(4S)-methyl-α-(4-benzyloxycarbonyl-2-oxoazetidine-1-yl)-α-(phenyl) acetate.
Claim 31
Dependent Claim
2 words
(4S)-methyl-α-(4-benzyloxycarbonyl-2-oxoazetidine-1-yl)-α-(3-methoxyphenyl) acetate.
Claim 32
Dependent Claim
2 words
(4S)-methyl-α-(4-benzyloxycarbonyl-2-oxoazetidine-1-yl)-α-(3-methoxyphenyl) acetate.
Claim 33
Dependent Claim
2 words
(4S)-methyl-α-(4-benzyloxycarbonyl-2-oxoazetidine-1-yl)-α-(5-methylfuran-2-yl) acetate.
Claim 34
Dependent Claim
2 words
(4S)-methyl-α-(4-benzyloxycarbonyl-2-oxoazetidine-1-yl)-α-(5-methylfuran-2-yl) acetate.
Claim 35
Dependent Claim
2 words
(4S)-methyl-α-(4-carbonyl-2-oxoazetidine-1-yl)-α-(phenyl) acetate.
Claim 36
Dependent Claim
2 words
(4S)-methyl-α-(4-carbonyl-2-oxoazetidine-1-yl)-α-(phenyl) acetate.
Claim 37
Dependent Claim
2 words
(4S)-methyl-α-(4-carboxyl-2-oxoazetidine-1-yl)-α-(3-methoxyphenyl) acetate.
Claim 38
Dependent Claim
2 words
(4S)-methyl-α-(4-carboxyl-2-oxoazetidine-1-yl)-α-(3-methoxyphenyl) acetate.
Claim 39
Dependent Claim
2 words
(4S)-methyl-α-(4-carboxyl-2-oxoazetidine-1-yl)-α-(5-methylfuran-2-yl) acetate.
Claim 40
Dependent Claim
2 words
(4S)-methyl-α-(4-carboxyl-2-oxoazetidine-1-yl)-α-(5-methylfuran-2-yl) acetate.
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) | 1985-03-29 | 1985-09-28 | 1986-03-30 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1989-03-29 | 1989-09-28 | 1990-03-30 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1993-03-29 | 1993-09-28 | 1994-03-30 | $7700.00 | Window Closed / Lapsed |