Patent US4013648A successfully refreshed from Google Patents.
US4013648A
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US
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Δ2,3 -0-2-Isocephem-4-carboxylic acid and derivatives as antibacterial agents
Assignee: Bristol Myers Co
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Filing: 1975-07-23
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Granted: 1977-03-22
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Expires: 1995-07-23
Abstract
Abstract There is described the stereoselective total synthesis of novel Δ 2 ,3 -1,4-morpholine-2-carboxylic acids possessing a fused β-lactam ring in the 1,6-position and carrying a substituent cis to carbon 5 in the 7-position of the fused ring system represented by the general formula ##STR1## wherein X is amino and Z represents an optionally substituted heterocyclic ring containing N, O or S. Also included in the invention are compounds of formula I in which the carboxyl group at the 2-position is protected as by an easily cleavable ester group and salts of both the free acids and carboxyl-protected compounds of formula I. The compounds of formula I are potent antibacterial agents or are of use as intermediates in the preparation of such anti-bacterial agents.
Inventors
- 👤 Donald E. Horning
- 👤 Leeson R. Morris
- 👤 James L. Douglas
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-08 14:47
CPC Classifications
C; C07; C07D; C07D257/00; C07D257/02; C07D257/04; A; A61; A61P; A61P31/00; A61P31/04; C07D205/00; C07D205/02; C07D205/06; C07D205/08; C07D205/085; C07D317/00; C07D317/08; C07D317/10; C07D317/14; C07D317/30
Claims Analysis
Total Claims: 25
Claim 1
Independent Claim
124 words
The compound of the formula ##STR173## wherein R" is hydrogen or an easily cleavable ester carboxyl-protecting group and Z represents a 5- or 6-membered heterocyclic ring containing N, O or S, said heterocyclic ring being optionally substituted by one or two substituents selected from the group consisting of halo, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, cyano, carboxyl, amino, nitro, C 3 -C 4 cycloalkyl, C 2 -C 4 alkenyl, trifluoromethyl, hydroxy, hydroxymethyl, C 1 -C 4 alkylthio, C 1 -C 4 alkylamino, di(C 1 -C 4 alkyl)amino, mercapto, phenyl, benzyl, alkoxyalkyl of up to 4 carbons and -(CH 2 ) n COOH in which n is an integer of 1 to 4, or carboxylic acid or acid addition salts thereof.
Claim 2
Dependent Claim
124 words
The compound of the formula ##STR173## wherein R" is hydrogen or an easily cleavable ester carboxyl-protecting group and Z represents a 5- or 6-membered heterocyclic ring containing N, O or S, said heterocyclic ring being optionally substituted by one or two substituents selected from the group consisting of halo, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, cyano, carboxyl, amino, nitro, C 3 -C 4 cycloalkyl, C 2 -C 4 alkenyl, trifluoromethyl, hydroxy, hydroxymethyl, C 1 -C 4 alkylthio, C 1 -C 4 alkylamino, di(C 1 -C 4 alkyl)amino, mercapto, phenyl, benzyl, alkoxyalkyl of up to 4 carbons and -(CH 2 ) n COOH in which n is an integer of 1 to 4, or carboxylic acid or acid addition salts thereof.
Claim 3
Dependent Claim
124 words
An acid, ester or salt of claim 1 wherein Z represents a heterocyclic radical selected from the group consisting of thienyl, furyl, pyrazolyl, imidazolyl, isoimidazolyl, triazolyl, tetrazolyl, thiazolyl, thiadiazolyl, oxazolyl, oxadiazolyl, isothiazolyl, isoxazolyl, pyridyl, pryidazinyl, pyrazinyl, pyrimidinyl and triazinyl, said heterocyclic radical being optionally substituted by one or two substituents selected from the group consisting of halo, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, cyano, carboxyl, amino, nitro, C 3 -C 4 cycloalkyl, C 2 -C 4 alkenyl, trifluoromethyl, hydroxy, hydroxymethyl, C 1 -C 4 alkylthio, C 1 -C 4 alkylamino, di(C 1 -C 4 alkyl)amino, mercapto, phenyl, benzyl, alkoxyalkyl of up to 4 carbons and --(CH 2 ) n COOH in which n is an integer of 1 to 4.
Claim 4
Dependent Claim
102 words
An acid, ester or salt of claim 2 wherein Z represents a triazole, thiadiazole, oxadiazole or tetrazole radical, said radical being optionally substituted by one or two substituents selected from the group consisting of halo, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, cyano, carboxyl, amino, nitro, C 3 -C 4 cycloalkyl, C 2 -C 4 alkenyl, trifluoromethyl, hydroxy, hydroxymethyl, C 1 -C 4 alkylthio, C 1 -C 4 alkylamino, di(C 1 -C 4 alkyl)amino, phenyl, benzyl, mercapto, alkoxyalkyl of up to 4 carbons and --(CH 2 ) n COOH in which n is an integer of 1 to 4.
Claim 5
Dependent Claim
18 words
A compound of claim 1 wherein R" is hydrogen, or a carboxylic acid or acid addition salt thereof.
Claim 6
Dependent Claim
9 words
A compound of claim 1 wherein R" is hydrogen.
Claim 7
Dependent Claim
18 words
A compound of claim 2 wherein R" is hydrogen, or a carboxylic acid or acid addition salt thereof.
Claim 8
Dependent Claim
9 words
A compound of claim 2 wherein R" is hydrogen.
Claim 9
Dependent Claim
18 words
A compound of claim 3 wherein R" is hydrogen, or a carboxylic acid or acid addition salt thereof.
Claim 10
Dependent Claim
9 words
A compound of claim 3 wherein R" is hydrogen.
Claim 11
Dependent Claim
35 words
The compound of the formula ##STR174## wherein R" is hydrogen or an easily cleavable ester carboxyl-protecting group and Z represents 1,2,3-triazol-5-yl, 2-methyl-1,3,4-thiadiazol-5-yl, 2-methyl-1,3,4-oxadiazol-5-yl, 1-N-methyltetrazol-5-yl, 1-carboxymethyltetrazol-5-yl or 1-carboxyethyltetrazol-5-yl or carboxylic acid or acid addition salts thereof.
Claim 12
Dependent Claim
35 words
The compound of the formula ##STR174## wherein R" is hydrogen or an easily cleavable ester carboxyl-protecting group and Z represents 1,2,3-triazol-5-yl, 2-methyl-1,3,4-thiadiazol-5-yl, 2-methyl-1,3,4-oxadiazol-5-yl, 1-N-methyltetrazol-5-yl, 1-carboxymethyltetrazol-5-yl or 1-carboxyethyltetrazol-5-yl or carboxylic acid or acid addition salts thereof.
Claim 13
Dependent Claim
18 words
An acid of claim 10 wherein R" is hydrogen, or a carboxylic acid or acid addition salt thereof.
Claim 14
Dependent Claim
30 words
An ester of claim 10 wherein R" is benzyhydryl, benzyl, p-nitrobenzyl, p-methoxybenzyl, trichloroethyl, trimethylsilyl, phenacyl, acetonyl, (lower)alkyl, triphenylmethyl, methoxymethyl, indanyl, phthalidyl, pivaloxymethyl or acetoxymethyl, or an acid addition salt thereof.
Claim 15
Dependent Claim
9 words
The acid of claim 10 wherein Z is 1,2,3-triazol-5-yl.
Claim 16
Dependent Claim
9 words
The acid of claim 10 wherein Z is 2-methyl-1,3,4-thiadiazol-5-yl.
Claim 17
Dependent Claim
9 words
The acid of claim 10 wherein Z is 2-methyl-1,3,4-oxadiazol-5-yl.
Claim 18
Dependent Claim
9 words
The acid of claim 10 wherein Z is 1-N-methyltetrazol-5-yl.
Claim 19
Dependent Claim
9 words
The acid of claim 10 wherein Z is 1-carboxymethyltetrazol-5-yl.
Claim 20
Dependent Claim
9 words
The acid of claim 10 wherein Z is 1-carboxyethyltetrazol-5-yl.
Claim 21
Dependent Claim
10 words
The ester of claim 10 named p-nitrobenzyl 7β-amino-3-(1-methyltetrazol-5-ylthiomethyl)-Δ 3 -0-2-isocephem-4-carboxylate.
Claim 22
Dependent Claim
10 words
The ester of claim 10 named benzyl 7β-amino-3-(1-methyltetrazol-5-ylthiomethyl)-Δ 3 -0-2-isocephem-4-carboxylate.
Claim 23
Dependent Claim
10 words
The ester of claim 10 named p-nitrobenzyl 7β-amino-3-(2-methyl-1,3,4-thiadiazol-5-ylthiomethyl)-Δ 3 -0-2-isocephem-4-carboxylate.
Claim 24
Dependent Claim
10 words
The ester of claim 10 named p-nitrobenzyl 7β-amino-3-(2-methyl-1,3,4-oxadiazol-5-ylthiomethyl)-Δ 3 -0-2-isocephem-4-carboxylate.
Claim 25
Dependent Claim
9 words
An acid of claim 10 wherein R" is hydrogen.
References Cited (Backward Citations)
DE1914366A1
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
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| 3.5 Years (Year 4) | 1980-03-21 | 1980-09-20 | 1981-03-22 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1984-03-21 | 1984-09-20 | 1985-03-22 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1988-03-21 | 1988-09-20 | 1989-03-22 | $7700.00 | Window Closed / Lapsed |