US4444771A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Azeto triazolo pyrazine β-lactam antibacterial agents
Assignee: Beecham Group PLC
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Filing: 1981-09-04
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Granted: 1984-04-24
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Expires: 2001-09-04
Abstract
Abstract A compound of formula (I) or a salt thereof: ##STR1## wherein R 1 is an amino group, an azido group, or an acylamino group as found in antibacterially active penicillins or cephalosporins; R 2 is a hydrogen atom or a C 1-4 alkyl group; R 3 is a hydrogen atom, or a C 1-4 alkyl group optionally substituted by a carboxyl, carboxylic ester, hydroxy, C 1-4 alkyloxy, acyloxy or heterocyclylthio group; and R 4 is hydrogen or a readily removable carboxyl protecting group. The compounds wherein R 1 is an acylamino group are found in known antibacterially active penicillins and cephalosporins and wherein R 4 is a hydrogen, a pharmaceutically acceptable salting ion or an in vivo hydrolyzable ester forming radical may be formulated in pharmaceutical compositions. Processes for the preparation of the compound (I) are also described.
Inventors
- 👤 Michael J. Pearson
- 👤 Clive L. Branch
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-05 22:14
CPC Classifications
C; C07; C07D; C07D487/00; C07D487/12; C07D487/14; A; A61; A61P; A61P31/00; A61P31/04; C07D205/00; C07D205/02; C07D205/06; C07D205/08; C07D205/085; C07F; C07F7/00; C07F7/02; C07F7/08; C07F7/0803; C07F7/081; C07F7/0812; Y; Y02; Y02P; Y02P20/00; Y02P20/50; Y02P20/55
Claims Analysis
Total Claims: 24
Claim 1
Independent Claim
285 words
A compound of the formula (I): ##STR50## a pharmaceutically acceptable salt thereof or a pharmaceutically acceptable in-vivo hydrolyzable ester thereof wherein R 1 is amino, azido or a moiety of the formula R 5 --CO--NH wherein R 5 is of the sub-formulae (a)-(d): ##STR51## wherein n is 0, 1 or 2; m is 0, 1 or 2; A 1 is alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 6 carbon atoms, cyclohexenyl, cyclohexadienyl, phenyl, hydroxy-phenyl, thienyl or pyridyl; X is hydrogen, halo, carboxy, a pharmaceutically acceptable carboxyl ester moiety, azido, tetrazolyl, hydroxy, acyloxy, amino, ureido, guanidino or acylureido; A 2 is phenyl, 2,6-dimethoxyphenyl, 2-alkoxy-1-naphthyl, 3-phenylisoxazolyl or 3-phenyl-5-methylisoxazolyl; X 1 is CH 2 OCH 2 , CH 2 SCH 2 or (CH 2 ) n wherein n is as above defined; and X 2 is an oxygen or sulphur atom; R 2 is hydrogen or alkyl of 1 to 4 carbon atoms; R 3 is hydrogen, alkyl of 1 to 4 carbon atoms unsubstituted or mono-substituted by carboxy, a pharmaceutically acceptable carboxyl ester moiety, hydroxy, alkyloxy of 1 to 4 carbon atoms, acyloxy or heterocyclylthio of the formula --S--Het wherein Het is diazolyl, triazolyl, tetrazolyl, thiazolyl, thiadiazolyl, thiatriazolyl, oxazolyl or oxadiazolyl unsubstituted or substituted with one or two substituents selected from the group consisting of alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, hydroxyalkyl of 1 to 6 carbon atoms, alkenyl of 1 to 6 carbon atoms, alkoxyalkyl of 1 to 6 carbon atoms in each of the alkoxy and alkyl moieties, carboxyalkyl of 1 to 6 carbon atoms, alkylsulphonyl of 1 to 6 carbon atoms, carbamoyl, carbamoylmethyl, trifluoromethyl, hydroxy and halo; and R 4 is hydrogen.
Claim 2
Dependent Claim
285 words
A compound of the formula (I): ##STR50## a pharmaceutically acceptable salt thereof or a pharmaceutically acceptable in-vivo hydrolyzable ester thereof wherein R 1 is amino, azido or a moiety of the formula R 5 --CO--NH wherein R 5 is of the sub-formulae (a)-(d): ##STR51## wherein n is 0, 1 or 2; m is 0, 1 or 2; A 1 is alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 6 carbon atoms, cyclohexenyl, cyclohexadienyl, phenyl, hydroxy-phenyl, thienyl or pyridyl; X is hydrogen, halo, carboxy, a pharmaceutically acceptable carboxyl ester moiety, azido, tetrazolyl, hydroxy, acyloxy, amino, ureido, guanidino or acylureido; A 2 is phenyl, 2,6-dimethoxyphenyl, 2-alkoxy-1-naphthyl, 3-phenylisoxazolyl or 3-phenyl-5-methylisoxazolyl; X 1 is CH 2 OCH 2 , CH 2 SCH 2 or (CH 2 ) n wherein n is as above defined; and X 2 is an oxygen or sulphur atom; R 2 is hydrogen or alkyl of 1 to 4 carbon atoms; R 3 is hydrogen, alkyl of 1 to 4 carbon atoms unsubstituted or mono-substituted by carboxy, a pharmaceutically acceptable carboxyl ester moiety, hydroxy, alkyloxy of 1 to 4 carbon atoms, acyloxy or heterocyclylthio of the formula --S--Het wherein Het is diazolyl, triazolyl, tetrazolyl, thiazolyl, thiadiazolyl, thiatriazolyl, oxazolyl or oxadiazolyl unsubstituted or substituted with one or two substituents selected from the group consisting of alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, hydroxyalkyl of 1 to 6 carbon atoms, alkenyl of 1 to 6 carbon atoms, alkoxyalkyl of 1 to 6 carbon atoms in each of the alkoxy and alkyl moieties, carboxyalkyl of 1 to 6 carbon atoms, alkylsulphonyl of 1 to 6 carbon atoms, carbamoyl, carbamoylmethyl, trifluoromethyl, hydroxy and halo; and R 4 is hydrogen.
Claim 3
Dependent Claim
274 words
A compound according to claim 1 of the formula (II): ##STR52## a pharmaceutically acceptable salt thereof or a pharmaceutically acceptable in-vivo hydrolyzable ester thereof wherein R 2 is hydrogen or alkyl of 1 to 4 carbon atoms; R 3 is hydrogen, alkyl of 1 to 4 carbon atoms unsubstituted or mono-substituted by carboxy, a pharmaceutically acceptable carboxyl moiety, hydroxy, alkyloxy of 1 to 4 carbon atoms, acyloxy or heterocyclylthio of the formula --S--Het wherein Het is diazolyl, triazolyl, tetrazolyl, thiazolyl, thiadiazolyl, thiatriazolyl, oxazolyl or oxadiazolyl unsubstituted or substituted with one or two substituents selected from the group consisting of alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, hydroxyalkyl of 1 to 6 carbon atoms, alkenyl of 1 to 6 carbon atoms, alkoxyalkyl of 1 to 6 carbon atoms in each of the alkoxy and alkyl moieties, carboxyalkyl of 1 to 6 carbon atoms, alkylsulphonyl of 1 to 6 carbon atoms, carbamoyl, carbamoylmethyl, trifluoromethyl, hydroxy and halo; and R 5 is of the sub-formulae (a)-(d): ##STR53## wherein n is 0, 1 or 2; m is 0, 1 or 2; A 1 is alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 6 carbon atoms, cyclohexenyl, cyclohexadienyl, phenyl, hydroxy-phenyl, thienyl or pyridyl; X is hydrogen, halo, carboxy, a pharmaceutically acceptable carboxy ester moiety, azido, tetrazolyl, hydroxy, acyloxy, amino, ureido, guanidino or acylureido; A 2 is phenyl, 2,6-dimethoxyphenyl, 2-alkoxy-1-naphthyl, 3-phenylisoxazolyl or 3-phenyl-5-methylisoxazolyl; X 1 is CH 2 OCH 2 , CH 2 OCH 2 , CH 2 SCH 2 or (CH 2 ) n wherein n is as above defined; and X 2 is an oxygen or sulphur atom.
Claim 4
Dependent Claim
11 words
A compound according to claim 2 wherein R 2 is hydrogen.
Claim 5
Dependent Claim
116 words
A compound according to claim 2 wherein R 3 is hydrogen, methyl, ethyl, propyl, butyl, acetoxymethyl or heterocyclycthio methyl wherein the heterocyclylthio is of the formula --S--Het wherein Het is diazolyl, triazolyl, tetrazolyl, thiazolyl, thiadiazolyl, thiatriazolyl, oxazolyl or oxadiazolyl unsubstituted or substituted with one or two substituents selected from the group consisting of alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, hydroxyalkyl of 1 to 6 carbon atoms, alkenyl of 1 to 6 carbon atoms, alkoxyalkyl of 1 to 6 carbon atoms in each of the alkoxy and alkyl moieties, carboxyalkyl of 1 to 6 carbon atoms, alkylsulphonyl of 1 to 6 carbon atoms, carbamoyl, carbamoylmethyl, trifluoromethyl, hydroxy and halo.
Claim 6
Dependent Claim
56 words
A compound according to claim 2 wherein R 5 is a group of the sub-formulae (e) or (f): ##STR54## wherein R 6 is phenyl, thienyl or phenoxy; R 7 is hydrogen or methyl; R 8 is phenyl, p-hydroxyphenyl, thienyl or cyclohexadienyl; and R 9 is hydroxyl amino, carboxyl, lower alkyl, phenyl, tolyl or indanyl ester thereof.
Claim 7
Dependent Claim
23 words
A compound according to claim 2 wherein R 5 CO is a D-phenylglycyl, D-p-hydroxyphenylglycyl, D-mandelyl, malonyl, benzoyl, 2-thienylacetyl, 3-thienylacetyl, 2-thienyl-α-carboxyacetyl, 3-thienyl-α-carboxyacetyl or phenoxyacetyl.
Claim 8
Dependent Claim
13 words
A compound according to claim 2 wherein R 1 is amino or azido.
Claim 9
Dependent Claim
309 words
A pharmaceutical composition useful for treating bacterial infections in animals which comprises an antibacterially effective amount of a compound of the formula (I): ##STR55## a pharmaceutically acceptable salt thereof or a pharmaceutically acceptable in-vivo hydrolyzable ester thereof wherein R 1 is amino, azido or a moiety of the formula R 5 --CO--NH wherein R 5 is of the sub-formulae (a)-(d): ##STR56## wherein n is 0, 1 or 2; m is 0, 1 or 2; A 1 is alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 6 carbon atoms, cyclohexenyl, cyclohexadienyl, phenyl, hydroxy-phenyl, thienyl or pyridyl; X is hydrogen, halo, carboxy, a pharmaceutically acceptable carboxyl ester moiety, azido, tetrazolyl, hydroxy, acyloxy, amino, ureido, guanidino or acylureido; A 2 is phenyl, 2,6-dimethoxyphenyl, 2-alkoxy-1-naphthyl, 3-phenylisoxazolyl or 3-phenyl-5-methylisoxazolyl; X 1 is CH 2 OCH 2 , CH 2 SCH 2 or (CH 2 ) n wherein n is as above defined; and X 2 is an oxygen or sulphur atom; R 2 is hydrogen or alkyl of 1 to 4 carbon atoms; R 3 is hydrogen, alkyl of 1 to 4 carbon atoms unsubstituted or mono-substituted by carboxy, a pharmaceutically acceptable carboxyl ester moiety, hydroxy, alkyloxy of 1 to 4 carbon atoms, acyloxy or heterocyclylthio of the formula --S--Het wherein Het is diazolyl, triazolyl, tetrazolyl, thiazolyl, thiadiazolyl, thiatriazolyl, oxazolyl or oxadiazolyl unsubstituted or substituted with one or two substituents selected from the group consisting of alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, hydroxyalkyl of 1 to 6 carbon atoms, alkenyl of 1 to 6 carbon atoms, alkoxyalkyl of 1 to 6 carbon atoms in each of the alkoxy and alkyl moieties, carboxyalkyl of 1 to 6 carbon atoms, alkylsulphonyl of 1 to 6 carbon atoms, carbamoyl, carbamoylmethyl, trifluoromethyl, hydroxy and halo; and R 4 is hydrogen, in combination with a pharmaceutically acceptable carrier.
Claim 10
Dependent Claim
309 words
A pharmaceutical composition useful for treating bacterial infections in animals which comprises an antibacterially effective amount of a compound of the formula (I): ##STR55## a pharmaceutically acceptable salt thereof or a pharmaceutically acceptable in-vivo hydrolyzable ester thereof wherein R 1 is amino, azido or a moiety of the formula R 5 --CO--NH wherein R 5 is of the sub-formulae (a)-(d): ##STR56## wherein n is 0, 1 or 2; m is 0, 1 or 2; A 1 is alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 6 carbon atoms, cyclohexenyl, cyclohexadienyl, phenyl, hydroxy-phenyl, thienyl or pyridyl; X is hydrogen, halo, carboxy, a pharmaceutically acceptable carboxyl ester moiety, azido, tetrazolyl, hydroxy, acyloxy, amino, ureido, guanidino or acylureido; A 2 is phenyl, 2,6-dimethoxyphenyl, 2-alkoxy-1-naphthyl, 3-phenylisoxazolyl or 3-phenyl-5-methylisoxazolyl; X 1 is CH 2 OCH 2 , CH 2 SCH 2 or (CH 2 ) n wherein n is as above defined; and X 2 is an oxygen or sulphur atom; R 2 is hydrogen or alkyl of 1 to 4 carbon atoms; R 3 is hydrogen, alkyl of 1 to 4 carbon atoms unsubstituted or mono-substituted by carboxy, a pharmaceutically acceptable carboxyl ester moiety, hydroxy, alkyloxy of 1 to 4 carbon atoms, acyloxy or heterocyclylthio of the formula --S--Het wherein Het is diazolyl, triazolyl, tetrazolyl, thiazolyl, thiadiazolyl, thiatriazolyl, oxazolyl or oxadiazolyl unsubstituted or substituted with one or two substituents selected from the group consisting of alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, hydroxyalkyl of 1 to 6 carbon atoms, alkenyl of 1 to 6 carbon atoms, alkoxyalkyl of 1 to 6 carbon atoms in each of the alkoxy and alkyl moieties, carboxyalkyl of 1 to 6 carbon atoms, alkylsulphonyl of 1 to 6 carbon atoms, carbamoyl, carbamoylmethyl, trifluoromethyl, hydroxy and halo; and R 4 is hydrogen, in combination with a pharmaceutically acceptable carrier.
Claim 11
Dependent Claim
278 words
A composition according to claim 8 wherein the compound is of the formula (II): ##STR57## a pharmaceutically acceptable salt thereof or a pharmaceutically acceptable in-vivo hydrolyzable ester thereof wherein R 2 is hydrogen or alkyl of 1 to 4 carbon atoms; R 3 is hydrogen, alkyl of 1 to 4 carbon atoms unsubstituted or mono-substituted by carboxy, a pharmaceutically acceptable carboxyl moiety, hydroxy, alkyloxy of 1 to 4 carbon atoms, acyloxy or heterocyclylthio of the formula --S--Het wherein Het is diazolyl, triazolyl, tetrazolyl, thiazolyl, thiadiazolyl, thiatriazolyl, oxazolyl or oxadiazolyl unsubstituted or substituted with one or two substituents selected from the group consisting of alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, hydroxyalkyl of 1 to 6 carbon atoms, alkenyl of 1 to 6 carbon atoms, alkoxyalkyl of 1 to 6 carbon atoms in each of the alkoxy and alkyl moieties, carboxyalkyl of 1 to 6 carbon atoms, alkylsulphonyl of 1 to 6 carbon atoms, carbamoyl, carbamoylmethyl, trifluoromethyl, hydroxy and halo; and R 5 is of the sub-formulae (a)-(d): ##STR58## wherein n is 0, 1 or 2; m is 0, 1 or 2; A 1 is alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 6 carbon atoms, cyclohexenyl, cyclohexadienyl, phenyl, hydroxy-phenyl, thienyl or pyridyl; X is hydrogen, halo, carboxy, a pharmaceutically acceptable carboxy ester moiety, azido, tetrazolyl, hydroxy, acyloxy, amino, ureido, guanidino or acylureido; A 2 is phenyl, 2,6-dimethoxyphenyl, 2-alkoxy-1-naphthyl, 3-phenylisoxazolyl or 3-phenyl-5-methylisoxazolyl; X 1 is CH 2 OCH 2 , CH 2 OCH 2 , CH 2 SCH 2 or (CH 2 ) n wherein n is as above defined; and X 2 is an oxygen or sulphur atom.
Claim 12
Dependent Claim
11 words
A composition according to claim 9 wherein R 2 is hydrogen.
Claim 13
Dependent Claim
116 words
A composition according to claim 9 wherein R 3 is hydrogen, methyl, ethyl, propyl, butyl, acetoxymethyl or heterocyclycthio methyl wherein the heterocyclycthio is of the formula --S--Het wherein Het is diazolyl, triazolyl, tetrazolyl, thiazolyl, thiadiazolyl, thiatriazolyl, oxazolyl or oxadiazolyl unsubstituted or substituted with one or two substituents selected from the group consisting of alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, hydroxyalkyl of 1 to 6 carbon atoms, alkenyl of 1 to 6 carbon atoms, alkoxyalkyl of 1 to 6 carbon atoms in each of the alkoxy and alkyl moieties, carboxyalkyl of 1 to 6 carbon atoms, alkylsulphonyl of 1 to 6 carbon atoms, carbamoyl, carbamoylmethyl, trifluoromethyl, hydroxy and halo.
Claim 14
Dependent Claim
56 words
A composition according to claim 9 wherein R 5 is a group of the sub-formulae (e) or (f): ##STR59## wherein R 6 is phenyl, thienyl or phenoxy; R 7 is hydrogen or methyl R 8 is phenyl, p-hydroxyphenyl, thienyl or cyclohexadienyl; and R 9 is hydroxyl amino, carboxyl, lower alkyl, phenyl, tolyl or indanyl ester thereof.
Claim 15
Dependent Claim
23 words
A composition according to claim 9 wherein R 5 CO is a D-phenylglycyl, D-p-hydroxyphenylglycyl, D-mandelyl, malonyl, benzoyl, 2-thienylacetyl, 3-thienylacetyl, 2-thienyl-α-carboxyacetyl, 3-thienyl-α-carboxyacetyl or phenoxyacetyl.
Claim 16
Dependent Claim
13 words
A composition according to claim 9 wherein R 1 is amino or azido.
Claim 17
Independent Claim
318 words
A method of treating bacterial infections in humans and animals which comprises administering to a human or animal in need thereof an antibacterially effective amount of a compound of the formula (I): ##STR60## a pharmaceutically acceptable salt thereof or a pharmaceutically acceptable in-vivo hydrolyzable ester thereof wherein R 1 is amino, azido or a moiety of the formula R 5 --CO--NH wherein R 5 is of the sub-formulae (a)-(d): ##STR61## wherein n is 0, 1 or 2; m is 0, 1 or 2; A 1 is alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 6 carbon atoms, cyclohexenyl, cyclohexadienyl, phenyl, hydroxy-phenyl, thienyl or pyridyl; X is hydrogen, halo, carboxy, a pharmaceutically acceptable carboxyl ester moiety, azido, tetrazolyl, hydroxy, acyloxy, amino, ureido, guanidino or acylureido; A 2 is phenyl, 2,6-dimethoxyphenyl, 2-alkoxy-1-naphthyl, 3-phenylisoxazolyl or 3-phenyl-5-methylisoxazolyl; X 1 is CH 2 OCH 2 , CH 2 SCH 2 or (CH 2 ) n wherein n is as above defined; and X 2 is an oxygen or sulphur atom; R 2 is hydrogen or alkyl of 1 to 4 carbon atoms; R 3 is hydrogen, alkyl of 1 to 4 carbon atoms unsubstituted or mono-substituted by carboxy, a pharmaceutically acceptable carboxyl ester moiety, hydroxy, alkyloxy of 1 to 4 carbon atoms, acyloxy or heterocyclylthio of the formula --S--Het wherein Het is diazolyl, triazolyl, tetrazolyl, thiazolyl, thiadiazolyl, thiatriazolyl, oxazolyl or oxadiazolyl unsubstituted or substituted with one or two substituents selected from the group consisting of alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, hydroxyalkyl of 1 to 6 carbon atoms, alkenyl of 1 to 6 carbon atoms, alkoxyalkyl of 1 to 6 carbon atoms in each of the alkoxy and alkyl moieties, carboxyalkyl of 1 to 6 carbon atoms, alkylsulphonyl of 1 to 6 carbon atoms, carbamoyl, carbamoylmethyl, trifluoromethyl, hydroxy and halo; and R 4 is hydrogen, in combination with a pharmaceutically acceptable carrier.
Claim 18
Independent Claim
318 words
A method of treating bacterial infections in humans and animals which comprises administering to a human or animal in need thereof an antibacterially effective amount of a compound of the formula (I): ##STR60## a pharmaceutically acceptable salt thereof or a pharmaceutically acceptable in-vivo hydrolyzable ester thereof wherein R 1 is amino, azido or a moiety of the formula R 5 --CO--NH wherein R 5 is of the sub-formulae (a)-(d): ##STR61## wherein n is 0, 1 or 2; m is 0, 1 or 2; A 1 is alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 6 carbon atoms, cyclohexenyl, cyclohexadienyl, phenyl, hydroxy-phenyl, thienyl or pyridyl; X is hydrogen, halo, carboxy, a pharmaceutically acceptable carboxyl ester moiety, azido, tetrazolyl, hydroxy, acyloxy, amino, ureido, guanidino or acylureido; A 2 is phenyl, 2,6-dimethoxyphenyl, 2-alkoxy-1-naphthyl, 3-phenylisoxazolyl or 3-phenyl-5-methylisoxazolyl; X 1 is CH 2 OCH 2 , CH 2 SCH 2 or (CH 2 ) n wherein n is as above defined; and X 2 is an oxygen or sulphur atom; R 2 is hydrogen or alkyl of 1 to 4 carbon atoms; R 3 is hydrogen, alkyl of 1 to 4 carbon atoms unsubstituted or mono-substituted by carboxy, a pharmaceutically acceptable carboxyl ester moiety, hydroxy, alkyloxy of 1 to 4 carbon atoms, acyloxy or heterocyclylthio of the formula --S--Het wherein Het is diazolyl, triazolyl, tetrazolyl, thiazolyl, thiadiazolyl, thiatriazolyl, oxazolyl or oxadiazolyl unsubstituted or substituted with one or two substituents selected from the group consisting of alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, hydroxyalkyl of 1 to 6 carbon atoms, alkenyl of 1 to 6 carbon atoms, alkoxyalkyl of 1 to 6 carbon atoms in each of the alkoxy and alkyl moieties, carboxyalkyl of 1 to 6 carbon atoms, alkylsulphonyl of 1 to 6 carbon atoms, carbamoyl, carbamoylmethyl, trifluoromethyl, hydroxy and halo; and R 4 is hydrogen, in combination with a pharmaceutically acceptable carrier.
Claim 19
Dependent Claim
278 words
A method according to claim 15 wherein the compound is of the formula (II): ##STR62## a pharmaceutically acceptable salt thereof or a pharmaceutically acceptable in-vivo hydrolyzable ester thereof wherein R 2 is hydrogen or alkyl of 1 to 4 carbon atoms; R 3 is hydrogen, alkyl of 1 to 4 carbon atoms unsubstituted or mono-substituted by carboxy, a pharmaceutically acceptable carboxyl moiety, hydroxy, alkyloxy of 1 to 4 carbon atoms, acyloxy or heterocyclylthio of the formula --S--Het wherein Het is diazolyl, triazolyl, tetrazolyl, thiazolyl, thiadiazolyl, thiatriazolyl, oxazolyl or oxadiazolyl unsubstituted or substituted with one or two substituents selected from the group consisting of alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, hydroxyalkyl of 1 to 6 carbon atoms, alkenyl of 1 to 6 carbon atoms, alkoxyalkyl of 1 to 6 carbon atoms in each of the alkoxy and alkyl moieties, carboxyalkyl of 1 to 6 carbon atoms, alkylsulphonyl of 1 to 6 carbon atoms, carbamoyl, carbamoylmethyl, trifluoromethyl, hydroxy and halo; and R 5 is of the sub-formulae (a)-(d): ##STR63## wherein n is 0, 1 or 2; m is 0, 1 or 2; A 1 is alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 6 carbon atoms, cyclohexenyl, cyclohexadienyl, phenyl, hydroxy-phenyl, thienyl or pyridyl; X is hydrogen, halo, carboxy, a pharmaceutically acceptable carboxy ester moiety, azido, tetrazolyl, hydroxy, acyloxy, amino, ureido, guanidino or acylureido; A 2 is phenyl, 2,6-dimethoxyphenyl, 2-alkoxy-1-naphthyl, 3-phenylisoxazolyl or 3-phenyl-5-methylisoxazolyl; X 1 is CH 2 OCH 2 , CH 2 OCH 2 , CH 2 SCH 2 or (CH 2 ) n wherein n is as above defined; and X 2 is an oxygen or sulphur atom.
Claim 20
Dependent Claim
11 words
A method according to claim 16 wherein R 2 is hydrogen.
Claim 21
Dependent Claim
116 words
A method according to claim 16 wherein R 3 is hydrogen, methyl, ethyl, propyl, butyl, acetoxymethyl or heterocyclycthio methyl wherein the heterocyclycthio is of the formula --S--Het wherein Het is diazolyl, triazolyl, tetrazolyl, thiazolyl, thiadiazolyl, thiatriazolyl, oxazolyl or oxadiazolyl unsubstituted or substituted with one or two substituents selected from the group consisting of alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, hydroxyalkyl of 1 to 6 carbon atoms, alkenyl of 1 to 6 carbon atoms, alkoxyalkyl of 1 to 6 carbon atoms in each of the alkoxy and alkyl moieties, carboxyalkyl of 1 to 6 carbon atoms, alkylsulphonyl of 1 to 6 carbon atoms, carbamoyl, carbamoylmethyl, trifluoromethyl, hydroxy and halo.
Claim 22
Dependent Claim
56 words
A method according to claim 16 wherein R 5 is a group of the sub-formulae (e) or (f): ##STR64## wherein R 6 is phenyl, thienyl or phenoxy; R 7 is hydrogen or methyl; R 8 is phenyl, p-hydroxyphenyl, thienyl or cyclohexadienyl; and R 9 is hydroxyl amino, carboxyl, lower alkyl, phenyl, tolyl or indanyl ester thereof.
Claim 23
Dependent Claim
23 words
A method according to claim 16 wherein R 5 CO is a D-phenylglycyl, D-p-hydroxyphenylglycyl, D-mandelyl, malonyl, benzoyl, 2-thienylacetyl, 3-thienylacetyl, 2-thienyl-α-carboxyacetyl, 3-thienyl-α-carboxyacetyl or phenoxyacetyl.
Claim 24
Dependent Claim
13 words
A method according to claim 16 wherein R 1 is amino or azido.
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| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
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| 3.5 Years (Year 4) | 1987-04-24 | 1987-10-24 | 1988-04-24 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1991-04-24 | 1991-10-24 | 1992-04-24 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1995-04-24 | 1995-10-24 | 1996-04-24 | $7700.00 | Window Closed / Lapsed |