US4569942A
Expired / Lapsed
US
⏱️ 0.0 years remaining
N,3-Disubstituted 2-oxindole-1-carboxamides as analgesic and antiinflammatory agents
Assignee: Pfizer Inc
•
Filing: 1985-03-22
•
Granted: 1986-02-11
•
Expires: 2005-03-22
Abstract
Abstract Certain 2-oxindole-1-carboxamide compounds having an acyl substituent at the 3-position, and also further substituted on the carboxamide nitrogen by an alkyl, cycloalkyl, phenyl or substituted phenyl group, are inhibitors of the cyclooxygenase (CO) and lipoxygenase (LO) enzymes, and are useful as analgesic and antiinflammatory agents in mammalian subjects. These 2-oxindole-1-carboxamide compounds are of particular value for ameliorating pain in human patients recovering from surgery or trauma, and alleviating the symptoms of chronic diseases, such as rheumatoid arthritis and osteoarthritis, in human subjects. Certain 2-oxindole-1-carboxamide compounds unsubstituted at C-3, but having a substituent on the carboxamide nitrogen, are useful as intermediates to the analgesic and antiinflammatory agents of the invention.
Inventors
- 👤 Saul B. Kadin
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-03 19:54
CPC Classifications
C; C07; C07D; C07D401/00; C07D401/02; C07D401/06; C07D209/00; C07D209/02; C07D209/04; C07D209/30; C07D209/32; C07D209/34; C07D209/56; C07D209/58; C07D209/60; C07D209/70; C07D405/00; C07D405/02; C07D405/06; C07D409/00; C07D409/02; C07D409/06; C07D491/00; C07D491/02; C07D491/04; C07D495/00; C07D495/02; C07D495/04
Claims Analysis
Total Claims: 63
Claim 1
Independent Claim
430 words
A 2-oxindole-1-carboxamide compound of the formula ##STR18## and the pharmaceutically-acceptable salts thereof; wherein X is selected from the group consisting of hydrogen, fluoro, chloro, bromo, alkyl having 1 to 4 carbons, cycloalkyl having 3 to 7 carbons, alkoxy having 1 to 4 carbons, alkylthio having 1 to 4 carbons, trifluoromethyl, alkylsulfinyl having 1 to 4 carbons, alkylsulfonyl having 1 to 4 carbons, nitro, phenyl, alkanoyl having 2 to 4 carbons, benzoyl, thenoyl, alkanamido having 2 to 4 carbons, benzamido and N,N-dialkylsulfamoyl having 1 to 3 carbons in each of said alkyls; and Y is selected from the group consisting of hydrogen, fluoro, chloro, bromo, alkyl having 1 to 4 carbons, cycloalkyl having 3 to 7 carbons, alkoxy having 1 to 4 carbons, alkylthio having 1 to 4 carbons and trifluoromethyl; or X and Y when taken together are a 4,5-, 5,6- or 6,7-methylenedioxy group or a 4,5-, 5,6- or 6,7-ethylenedioxy group; or X and Y when taken together and when attached to adjacent carbon atoms form a divalent radical Z, wherein Z is selected from the group consisting of ##STR19## wherein W is oxygen or sulfur; R 1 is selected from the group consisting of alkyl having 1 to 6 carbons, cycloalkyl having 3 to 7 carbons, cycloalkenyl having 4 to 7 carbons, phenyl, substituted phenyl, phenylalkyl having 1 to 3 carbons in said alkyl, (substituted phenyl)alkyl having 1 to 3 carbons in said alkyl, phenoxyalkyl having 1 to 3 carbons in said alkyl, (substituted phenoxy)alkyl having 1 to 3 carbons in said alkyl, (thiophenoxy)alkyl having 1 to 3 carbons in said alkyl, naphthyl, bicyclo[2.2.1]heptan-2-yl, bicyclo[2.2.1]hept-5-en-2-yl and --(CH 2 ) n --Q--R°; wherein the substituent on said substituted phenyl, said (substituted phenyl)alkyl and said (substituted phenoxy)alkyl is selected from the group consisting of fluoro, chloro, bromo, alkyl having 1 to 4 carbons, alkoxy having 1 to 4 carbons and trifluoromethyl; n is zero, 1 or 2; Q is a divalent radical derived from a compound selected from the group consisting of furan, thiophene, pyrrole, pyrazole, imidazole, thiazole, isothiazole, oxazole, isoxazole, 1,2,3-thiadiazole, 1,3,4-thiadiazole, 1,2,5-thiadiazole, tetrahydrofuran, tetrahydrothiophene, tetrahydropyran, tetrahydrothiopyran, pyridine, pyrimidine, pyrazine, benzo[b]furan and benzo[b]thiophene; and R° is hydrogen or alkyl having 1 to 3 carbons. and R 2 is selected from the group consisting of alkyl having from 1 to 6 carbons, cycloalkyl having from 3 to 7 carbons, benzyl, furyl, thienyl, pyridyl and a group of the formula ##STR20## wherein R 3 and R 4 are each selected from the group consisting of hydrogen, fluoro, chloro, alkyl having 1 to 4 carbons, alkoxy having 1 to 4 carbons and trifluoromethyl.
Claim 2
Dependent Claim
430 words
A 2-oxindole-1-carboxamide compound of the formula ##STR18## and the pharmaceutically-acceptable salts thereof; wherein X is selected from the group consisting of hydrogen, fluoro, chloro, bromo, alkyl having 1 to 4 carbons, cycloalkyl having 3 to 7 carbons, alkoxy having 1 to 4 carbons, alkylthio having 1 to 4 carbons, trifluoromethyl, alkylsulfinyl having 1 to 4 carbons, alkylsulfonyl having 1 to 4 carbons, nitro, phenyl, alkanoyl having 2 to 4 carbons, benzoyl, thenoyl, alkanamido having 2 to 4 carbons, benzamido and N,N-dialkylsulfamoyl having 1 to 3 carbons in each of said alkyls; and Y is selected from the group consisting of hydrogen, fluoro, chloro, bromo, alkyl having 1 to 4 carbons, cycloalkyl having 3 to 7 carbons, alkoxy having 1 to 4 carbons, alkylthio having 1 to 4 carbons and trifluoromethyl; or X and Y when taken together are a 4,5-, 5,6- or 6,7-methylenedioxy group or a 4,5-, 5,6- or 6,7-ethylenedioxy group; or X and Y when taken together and when attached to adjacent carbon atoms form a divalent radical Z, wherein Z is selected from the group consisting of ##STR19## wherein W is oxygen or sulfur; R 1 is selected from the group consisting of alkyl having 1 to 6 carbons, cycloalkyl having 3 to 7 carbons, cycloalkenyl having 4 to 7 carbons, phenyl, substituted phenyl, phenylalkyl having 1 to 3 carbons in said alkyl, (substituted phenyl)alkyl having 1 to 3 carbons in said alkyl, phenoxyalkyl having 1 to 3 carbons in said alkyl, (substituted phenoxy)alkyl having 1 to 3 carbons in said alkyl, (thiophenoxy)alkyl having 1 to 3 carbons in said alkyl, naphthyl, bicyclo[2.2.1]heptan-2-yl, bicyclo[2.2.1]hept-5-en-2-yl and --(CH 2 ) n --Q--R°; wherein the substituent on said substituted phenyl, said (substituted phenyl)alkyl and said (substituted phenoxy)alkyl is selected from the group consisting of fluoro, chloro, bromo, alkyl having 1 to 4 carbons, alkoxy having 1 to 4 carbons and trifluoromethyl; n is zero, 1 or 2; Q is a divalent radical derived from a compound selected from the group consisting of furan, thiophene, pyrrole, pyrazole, imidazole, thiazole, isothiazole, oxazole, isoxazole, 1,2,3-thiadiazole, 1,3,4-thiadiazole, 1,2,5-thiadiazole, tetrahydrofuran, tetrahydrothiophene, tetrahydropyran, tetrahydrothiopyran, pyridine, pyrimidine, pyrazine, benzo[b]furan and benzo[b]thiophene; and R° is hydrogen or alkyl having 1 to 3 carbons. and R 2 is selected from the group consisting of alkyl having from 1 to 6 carbons, cycloalkyl having from 3 to 7 carbons, benzyl, furyl, thienyl, pyridyl and a group of the formula ##STR20## wherein R 3 and R 4 are each selected from the group consisting of hydrogen, fluoro, chloro, alkyl having 1 to 4 carbons, alkoxy having 1 to 4 carbons and trifluoromethyl.
Claim 3
Dependent Claim
134 words
A compound according to claim 1, wherein X is at the 5-position or the 6-position and it is selected from the group consisting of hydrogen, fluoro, chloro, bromo and trifluoromethyl; and Y is hydrogen; R 1 is selected from the group consisting of alkyl having from 1 to 6 carbons, cycloalkyl having from 3 to 7 carbons, furyl, thienyl, phenylalkyl having 1 to 3 carbons in said alkyl, furylmethyl, thienylmethyl and trifluoromethyl; and R 2 is selected from the group consisting of alkyl having from 1 to 6 carbons, cycloalkyl having from 3 to 7 carbons and a group of the formula ##STR21## wherein R 3 and R 4 are each selected from the group consisting of hydrogen, fluoro, chloro, alkyl having 1 to 4 carbons, alkoxy having 1 to 4 carbons and trifluoromethyl.
Claim 4
Dependent Claim
26 words
A compound according to claim 1, wherein X and Y are each selected from the group consisting of hydrogen, 5-fluoro, 6-fluoro, 5-chloro, 6-chloro, 5-trifluoromethyl and 6-trifluoromethyl.
Claim 5
Dependent Claim
22 words
A compound according to claim 3, wherein R 1 is selected from the group consisting of benzyl, 2-furyl, 2-thienyl, (2-furyl)methyl and (2-thienyl)methyl.
Claim 6
Dependent Claim
10 words
A compound according to claim 4, wherein Y is hydrogen.
Claim 7
Dependent Claim
19 words
A compound according to claim 5, wherein R 2 is selected from the group consisting of isopropyl and t-butyl.
Claim 8
Dependent Claim
12 words
A compound according to claim 6, wherein X is 5-chloro or 6-chloro.
Claim 9
Dependent Claim
19 words
The compound according to claim 7, wherein X is 5-chloro, R 1 is 2-furyl and R 2 is t-butyl.
Claim 10
Dependent Claim
19 words
The compound according to claim 7, wherein X is 6-chloro, R 1 is 2-thienyl and R 2 is t-butyl
Claim 11
Dependent Claim
10 words
A compound according to claim 6, wherein X is 5-fluoro.
Claim 12
Dependent Claim
16 words
The compound according to claim 10, wherein R 1 is 2-furyl and R 2 is t-butyl.
Claim 13
Dependent Claim
12 words
A compound according to claim 5, wherein R 2 is said ##STR22##
Claim 14
Dependent Claim
19 words
The compound according to claim 12, wherein X is hydrogen, R 1 is 2-thienyl and R 2 is 4-methoxyphenyl.
Claim 15
Dependent Claim
19 words
The compound according to claim 12, wherein X is hydrogen, R 1 is 2-furyl and R 2 is 2,4-difluorophenyl.
Claim 16
Dependent Claim
23 words
A compound according to claim 4, wherein X and Y are each selected from the group consisting of 5-fluoro, 6-fluoro, 5-chloro and 6-chloro.
Claim 17
Dependent Claim
19 words
A compound according to claim 15, wherein R 2 is selected from the group consisting of isopropyl and t-butyl.
Claim 18
Independent Claim
421 words
A method of eliciting an analgesic response in a mammalian subject, which comprises administering to said subject an analgesic response eliciting amount of a 2-oxindole-1-carboxamide compound of the formula ##STR23## or a pharmaceutically-acceptable salt thereof; wherein X is selected from the group consisting of hydrogen, fluoro, chloro, bromo, alkyl having 1 to 4 carbons, cycloalkyl having 3 to 7 carbons, alkoxy having 1 to 4 carbons, alkylthio having 1 to 4 carbons, trifluoromethyl, alkylsulfinyl having 1 to 4 carbons, alkylsulfonyl having 1 to 4 carbons, nitro, phenyl, alkanoyl having 2 to 4 carbons, benzoyl, thenoyl, alkanamido having 2 to 4 carbons, benzamido and N,N-dialkylsulfamoyl having 1 to 3 carbons in each of said alkyls; and Y is selected from the group consisting of hydrogen, fluoro, chloro, bromo, alkyl having 1 to 4 carbons, cycloalkyl having 3 to 7 carbons, alkoxy having 1 to 4 carbons, alkylthio having 1 to 4 carbons and trifluoromethyl; or X and Y when taken together are a 4,5-, 5,6-or 6,7-methylenedioxy group or a 4,5-, 5,6- or 6,7-ethylenedioxy group; or X and Y when taken together and when attached to adjacent carbon atoms form a divalent radical Z, wherein Z is selected from the group consisting of ##STR24## wherein W is oxygen or sulfur; R 1 is selected from the group consisting of alkyl having 1 to 6 carbons, cycloalkyl having 3 to 7 carbons, cycloalkenyl having 4 to 7 carbons, phenyl, substituted phenyl, phenylalkyl having 1 to 3 carbons in said alkyl, (substituted phenyl)alkyl having 1 to 3 carbons in said alkyl, phenoxyalkyl having 1 to 3 carbons in said alkyl, (substituted phenoxy)alkyl having 1 to 3 carbons in said alkyl, (thiophenoxy)alkyl having 1 to 3 carbons in said alkyl, naphthyl, bicyclo[2.2.1]heptan-2-yl, bicyclo[2.2.1]hept-5-en-2-yl and --(CH 2 ) n --Q--R°; wherein the substituent on said substituted phenyl, said (substituted phenyl)alkyl and said (substituted phenoxy)alkyl is selected from the group consisting of fluoro, chloro, bromo, alkyl having 1 to 4 carbons, alkoxy having 1 to 4 carbons and trifluoromethyl; n is zero, 1 or 2; Q is a divalent radical derived from a compound selected from the group consisting of furan, thiophene, pyrrole, pyrazole, imidazole, thiazole, isothiazole, oxazole, isoxazole, 1,2,3-thiadiazole, 1,3,4-thiadiazole, 1,2,5-thiadiazole, tetrahydrofuran, tetrahydrothiophene, tetrahydropyran, tetrahydrothiopyran, pyridine, pyrimidine, pyrazine, benzo[b]furan and benzo[b]thiophene; and R° is hydrogen or alkyl having 1 to 3 carbons; and R 2 is selected from the group consisting of alkyl having from 1 to 6 carbons, cycloalkyl having from 3 to 7 carbons, benzyl, furyl, thienyl, pyridyl and a group of the formula ##STR25##
Claim 19
Independent Claim
421 words
A method of eliciting an analgesic response in a mammalian subject, which comprises administering to said subject an analgesic response eliciting amount of a 2-oxindole-1-carboxamide compound of the formula ##STR23## or a pharmaceutically-acceptable salt thereof; wherein X is selected from the group consisting of hydrogen, fluoro, chloro, bromo, alkyl having 1 to 4 carbons, cycloalkyl having 3 to 7 carbons, alkoxy having 1 to 4 carbons, alkylthio having 1 to 4 carbons, trifluoromethyl, alkylsulfinyl having 1 to 4 carbons, alkylsulfonyl having 1 to 4 carbons, nitro, phenyl, alkanoyl having 2 to 4 carbons, benzoyl, thenoyl, alkanamido having 2 to 4 carbons, benzamido and N,N-dialkylsulfamoyl having 1 to 3 carbons in each of said alkyls; and Y is selected from the group consisting of hydrogen, fluoro, chloro, bromo, alkyl having 1 to 4 carbons, cycloalkyl having 3 to 7 carbons, alkoxy having 1 to 4 carbons, alkylthio having 1 to 4 carbons and trifluoromethyl; or X and Y when taken together are a 4,5-, 5,6-or 6,7-methylenedioxy group or a 4,5-, 5,6- or 6,7-ethylenedioxy group; or X and Y when taken together and when attached to adjacent carbon atoms form a divalent radical Z, wherein Z is selected from the group consisting of ##STR24## wherein W is oxygen or sulfur; R 1 is selected from the group consisting of alkyl having 1 to 6 carbons, cycloalkyl having 3 to 7 carbons, cycloalkenyl having 4 to 7 carbons, phenyl, substituted phenyl, phenylalkyl having 1 to 3 carbons in said alkyl, (substituted phenyl)alkyl having 1 to 3 carbons in said alkyl, phenoxyalkyl having 1 to 3 carbons in said alkyl, (substituted phenoxy)alkyl having 1 to 3 carbons in said alkyl, (thiophenoxy)alkyl having 1 to 3 carbons in said alkyl, naphthyl, bicyclo[2.2.1]heptan-2-yl, bicyclo[2.2.1]hept-5-en-2-yl and --(CH 2 ) n --Q--R°; wherein the substituent on said substituted phenyl, said (substituted phenyl)alkyl and said (substituted phenoxy)alkyl is selected from the group consisting of fluoro, chloro, bromo, alkyl having 1 to 4 carbons, alkoxy having 1 to 4 carbons and trifluoromethyl; n is zero, 1 or 2; Q is a divalent radical derived from a compound selected from the group consisting of furan, thiophene, pyrrole, pyrazole, imidazole, thiazole, isothiazole, oxazole, isoxazole, 1,2,3-thiadiazole, 1,3,4-thiadiazole, 1,2,5-thiadiazole, tetrahydrofuran, tetrahydrothiophene, tetrahydropyran, tetrahydrothiopyran, pyridine, pyrimidine, pyrazine, benzo[b]furan and benzo[b]thiophene; and R° is hydrogen or alkyl having 1 to 3 carbons; and R 2 is selected from the group consisting of alkyl having from 1 to 6 carbons, cycloalkyl having from 3 to 7 carbons, benzyl, furyl, thienyl, pyridyl and a group of the formula ##STR25##
Claim 20
Dependent Claim
31 words
wherein R 3 and R 4 are each selected from the group consisting of hydrogen, fluoro, chloro, alkyl having 1 to 4 carbons, alkoxy having 1 to 4 carbons and trifluoromethyl.
Claim 21
Dependent Claim
31 words
wherein R 3 and R 4 are each selected from the group consisting of hydrogen, fluoro, chloro, alkyl having 1 to 4 carbons, alkoxy having 1 to 4 carbons and trifluoromethyl.
Claim 22
Dependent Claim
134 words
The method according to claim 17, wherein X is at the 5-position or the 6-position and it is selected from the group consisting of hydrogen, fluoro, chloro, bromo and trifluoromethyl; and Y is hydrogen; R 1 is selected from the group consisting of alkyl having from 1 to 6 carbons, cycloalkyl having from 3 to 7 carbons, furyl, thienyl, phenylalkyl having 1 to 3 carbons in said alkyl, furylmethyl, thienylmethyl and trifluoromethyl; and R 2 is selected from the group consisting of alkyl having from 1 to 6 carbons, cycloalkyl having from 3 to 7 carbons and a group of the formula ##STR26## wherein R 3 and R 4 are each selected from the group consisting of hydrogen, fluoro, chloro, alkyl having 1 to 4 carbons, alkoxy having 1 to 4 carbons and trifluoromethyl.
Claim 23
Dependent Claim
26 words
The method according to claim 17, wherein X and Y are each selected from the group consisting of hydrogen, 5-fluoro, 6-fluoro, 5-chloro, 6-chloro, 5-trifluoromethyl and 6-trifluoromethyl.
Claim 24
Dependent Claim
22 words
The method according to claim 19, wherein R 1 is selected from the group consisting of benzyl, 2-furyl, 2-thienyl, (2-furyl)methyl and (2-thienyl)methyl.
Claim 25
Dependent Claim
10 words
The method according to claim 20, wherein Y is hydrogen.
Claim 26
Dependent Claim
19 words
The method according to claim 21, wherein R 2 is selected from the group consisting of isopropyl and t-butyl.
Claim 27
Dependent Claim
12 words
The method according to claim 22, wherein X is 5-chloro or 6-chloro.
Claim 28
Dependent Claim
19 words
The method according to claim 23, wherein X is 5-chloro, R 1 is 2-furyl and R 2 is t-butyl.
Claim 29
Dependent Claim
19 words
The method according to claim 23, wherein X is 6-chloro, R 1 is 2-thienyl and R 2 is t-butyl.
Claim 30
Dependent Claim
10 words
The method according to claim 22, wherein X is 5-fluoro.
Claim 31
Dependent Claim
16 words
The method according to claim 26, wherein R 1 is 2-furyl and R 2 is t-butyl.
Claim 32
Dependent Claim
12 words
The method according to claim 21, wherein R 2 is said ##STR27##
Claim 33
Dependent Claim
19 words
The method according to claim 28, wherein X is hydrogen, R 1 is 2-thienyl and R 2 is 4-methoxyphenyl.
Claim 34
Dependent Claim
19 words
The method according to claim 28, wherein X is hydrogen, R 1 is 2-furyl and R 2 is 2,4-difluorophenyl.
Claim 35
Dependent Claim
23 words
The method according to claim 20, wherein X and Y are each selected from the group consisting of 5-fluoro, 6-fluoro, 5-chloro and 6-chloro.
Claim 36
Dependent Claim
19 words
The method according to claim 31, wherein R 2 is selected from the group consisting of isopropyl and t-butyl.
Claim 37
Independent Claim
453 words
A method of treating an inflammatory disease in a mammalian subject, which comprises administering to said mammalian subject an inflammatory disease treating amount of a 2-oxindole-1-carboxamide compound of the formula ##STR28## or a pharmaceutically-acceptable salt thereof; wherein X is selected from the group consisting of hydrogen, fluoro, chloro, bromo, alkyl having 1 to 4 carbons, cycloalkyl having 3 to 7 carbons, alkoxy having 1 to 4 carbons, alkylthio having 1 to 4 carbons, trifluoromethyl, alkylsulfinyl having 1 to 4 carbons, alkylsulfonyl having 1 to 4 carbons, nitro, phenyl, alkanoyl having 2 to 4 carbons, benzoyl, thenoyl, alkanamido having 2 to 4 carbons, benzamido and N,N-dialkylsulfamoyl having 1 to 3 carbons in each of said alkyls; and Y is selected from the group consisting of hydrogen, fluoro, chloro, bromo, alkyl having 1 to 4 carbons, cycloalkyl having 3 to 7 carbons, alkoxy having 1 to 4 carbons, alkylthio having 1 to 4 carbons and trifluoromethyl; or X and Y when taken together are a 4,5-, 5,6-or 6,7-methylenedioxy group or a 4,5-, 5,6- or 6,7-ethylenedioxy group; or X and Y when taken together and when attached to adjacent carbon atoms form a divalent radical Z, wherein Z is selected from the group consisting of ##STR29## wherein W is oxygen or sulfur; R 1 is selected from the group consisting of alkyl having 1 to 6 carbons, cycloalkyl having 3 to 7 carbons, cycloalkenyl having 4 to 7 carbons, phenyl, substituted phenyl, phenylalkyl having 1 to 3 carbons in said alkyl, (substituted phenyl)alkyl having 1 to 3 carbons in said alkyl, phenoxyalkyl having 1 to 3 carbons in said alkyl, (substituted phenoxy)alkyl having 1 to 3 carbons in said alkyl, (thiophenoxy)alkyl having 1 to 3 carbons in said alkyl, naphthyl, bicyclo[2.2.1]heptan-2-yl, bicyclo[2.2.1]hept-5-en-2-yl and --(CH 2 ) n --Q--R°; wherein the substituent on said substituted phenyl, said (substituted phenyl)alkyl and said (substituted phenoxy)alkyl is selected from the group consisting of fluoro, chloro, bromo, alkyl having 1 to 4 carbons, alkoxy having 1 to 4 carbons and trifluoromethyl; n is zero, 1 or 2; Q is a divalent radical derived from a compound selected from the group consisting of furan, thiophene, pyrrole, pyrazole, imidazole, thiazole, isothiazole, oxazole, isoxazole, 1,2,3-thiadiazole, 1,3,4-thiadiazole, 1,2,5-thiadiazole, tetrahydrofuran, tetrahydrothiophene, tetrahydropyran, tetrahydrothiopyran, pyridine, pyrimidine, pyrazine, benzo[b]furan and benzo[b]thiophene; and R° is hydrogen or alkyl having 1 to 3 carbons; and R 2 is selected from the group consisting of alkyl having from 1 to 6 carbons, cycloalkyl having from 3 to 7 carbons, benzyl, furyl, thienyl, pyridyl and a group of the formula ##STR30## wherein R 3 and R 4 are each selected from the group consisting of hydrogen, fluoro, chloro, alkyl having 1 to 4 carbons, alkoxy having 1 to 4 carbons and trifluoromethyl.
Claim 38
Independent Claim
453 words
A method of treating an inflammatory disease in a mammalian subject, which comprises administering to said mammalian subject an inflammatory disease treating amount of a 2-oxindole-1-carboxamide compound of the formula ##STR28## or a pharmaceutically-acceptable salt thereof; wherein X is selected from the group consisting of hydrogen, fluoro, chloro, bromo, alkyl having 1 to 4 carbons, cycloalkyl having 3 to 7 carbons, alkoxy having 1 to 4 carbons, alkylthio having 1 to 4 carbons, trifluoromethyl, alkylsulfinyl having 1 to 4 carbons, alkylsulfonyl having 1 to 4 carbons, nitro, phenyl, alkanoyl having 2 to 4 carbons, benzoyl, thenoyl, alkanamido having 2 to 4 carbons, benzamido and N,N-dialkylsulfamoyl having 1 to 3 carbons in each of said alkyls; and Y is selected from the group consisting of hydrogen, fluoro, chloro, bromo, alkyl having 1 to 4 carbons, cycloalkyl having 3 to 7 carbons, alkoxy having 1 to 4 carbons, alkylthio having 1 to 4 carbons and trifluoromethyl; or X and Y when taken together are a 4,5-, 5,6-or 6,7-methylenedioxy group or a 4,5-, 5,6- or 6,7-ethylenedioxy group; or X and Y when taken together and when attached to adjacent carbon atoms form a divalent radical Z, wherein Z is selected from the group consisting of ##STR29## wherein W is oxygen or sulfur; R 1 is selected from the group consisting of alkyl having 1 to 6 carbons, cycloalkyl having 3 to 7 carbons, cycloalkenyl having 4 to 7 carbons, phenyl, substituted phenyl, phenylalkyl having 1 to 3 carbons in said alkyl, (substituted phenyl)alkyl having 1 to 3 carbons in said alkyl, phenoxyalkyl having 1 to 3 carbons in said alkyl, (substituted phenoxy)alkyl having 1 to 3 carbons in said alkyl, (thiophenoxy)alkyl having 1 to 3 carbons in said alkyl, naphthyl, bicyclo[2.2.1]heptan-2-yl, bicyclo[2.2.1]hept-5-en-2-yl and --(CH 2 ) n --Q--R°; wherein the substituent on said substituted phenyl, said (substituted phenyl)alkyl and said (substituted phenoxy)alkyl is selected from the group consisting of fluoro, chloro, bromo, alkyl having 1 to 4 carbons, alkoxy having 1 to 4 carbons and trifluoromethyl; n is zero, 1 or 2; Q is a divalent radical derived from a compound selected from the group consisting of furan, thiophene, pyrrole, pyrazole, imidazole, thiazole, isothiazole, oxazole, isoxazole, 1,2,3-thiadiazole, 1,3,4-thiadiazole, 1,2,5-thiadiazole, tetrahydrofuran, tetrahydrothiophene, tetrahydropyran, tetrahydrothiopyran, pyridine, pyrimidine, pyrazine, benzo[b]furan and benzo[b]thiophene; and R° is hydrogen or alkyl having 1 to 3 carbons; and R 2 is selected from the group consisting of alkyl having from 1 to 6 carbons, cycloalkyl having from 3 to 7 carbons, benzyl, furyl, thienyl, pyridyl and a group of the formula ##STR30## wherein R 3 and R 4 are each selected from the group consisting of hydrogen, fluoro, chloro, alkyl having 1 to 4 carbons, alkoxy having 1 to 4 carbons and trifluoromethyl.
Claim 39
Dependent Claim
134 words
The method according to claim 33, wherein X is at the 5-position or the 6-position and it is selected from the group consisting of hydrogen, fluoro, chloro, bromo and trifluoromethyl; and Y is hydrogen; R 1 is selected from the group consisting of alkyl having from 1 to 6 carbons, cycloalkyl having from 3 to 7 carbons, furyl, thienyl, phenylalkyl having 1 to 3 carbons in said alkyl, furylmethyl, thienylmethyl and trifluoromethyl; and R 2 is selected from the group consisting of alkyl having from 1 to 6 carbons, cycloalkyl having from 3 to 7 carbons and a group of the formula ##STR31## wherein R 3 and R 4 are each selected from the group consisting of hydrogen, fluoro, chloro, alkyl having 1 to 4 carbons, alkoxy having 1 to 4 carbons and trifluoromethyl.
Claim 40
Dependent Claim
26 words
The method according to claim 33, wherein X and Y are each selected from the group consisting of hydrogen, 5-fluoro, 6-fluoro, 5-chloro, 6-chloro, 5-trifluoromethyl and 6-trifluoromethyl.
Claim 41
Dependent Claim
22 words
The method according to claim 35, wherein R 1 is selected from the group consisting of benzyl, 2-furyl, 2-thienyl, (2-furyl)methyl and (2-thienyl)methyl.
Claim 42
Dependent Claim
10 words
The method according to claim 36, wherein Y is hydrogen.
Claim 43
Dependent Claim
19 words
The method according to claim 37, wherein R 2 is selected from the group consisting of isopropyl and t-butyl.
Claim 44
Dependent Claim
12 words
The method according to claim 38, wherein X is 5-chloro or 6-chloro.
Claim 45
Dependent Claim
19 words
The method according to claim 39, wherein X is 5-chloro, R 1 is 2-furyl and R 2 is t-butyl.
Claim 46
Dependent Claim
19 words
The method according to claim 39, wherein X is 6-chloro, R 1 is 2-thienyl and R 2 is t-butyl.
Claim 47
Dependent Claim
10 words
The method according to claim 38, wherein X is 5-fluoro.
Claim 48
Dependent Claim
16 words
The method according to claim 42, wherein R 1 is 2-furyl and R 2 is t-butyl.
Claim 49
Dependent Claim
12 words
The method according to claim 37, wherein R 2 is said ##STR32##
Claim 50
Dependent Claim
19 words
The method according to claim 44, wherein X is hydrogen, R 1 is 2-thienyl and R 2 is 4-methoxyphenyl.
Claim 51
Dependent Claim
19 words
The method according to claim 44, wherein X is hydrogen, R 1 is 2-furyl and R 2 is 2,4-difluorophenyl.
Claim 52
Dependent Claim
23 words
The method according to claim 36, wherein X and Y are each selected from the group consisting of 5-fluoro, 6-fluoro, 5-chloro and 6-chloro.
Claim 53
Dependent Claim
19 words
The method according to claim 47, wherein R 2 is selected from the group consisting of isopropyl and t-butyl.
Claim 54
Dependent Claim
58 words
A pharmaceutical composition, useful as an analgesic and antiinflammatory agent in a mammalian subject, which comprises a pharmaceutically-acceptable carrier and an analgesic response eliciting or inflammatory disease treating amount of a 2-oxindole-1-carboxamide compound according to claim 1, and wherein the weight ratio of the pharmaceutically-acceptable carrier to the 2-oxindole-1-carboxamide compound is in the range from 1:4 to 4:1.
Claim 55
Dependent Claim
101 words
A compound of the formula ##STR33## wherein X and Y are each selected from the group consisting of hydrogen, 5-fluoro, 6-fluoro, 5-chloro, 6-chloro, 5-trifluoromethyl and 6-trifluoromethyl, provided that X and Y are not both hydrogen; and R 2 is selected from the group consisting of alkyl having from 1 to 6 carbons, cycloalkyl having from 3 to 7 carbons, benzyl, furyl, thienyl, pyridyl and a group of the formula ##STR34## wherein R 3 and R 4 are each selected from the group consisting of hydrogen, fluoro, chloro, alkyl having 1 to 4 carbons, alkoxy having 1 to 4 carbons and trifluoromethyl.
Claim 56
Dependent Claim
101 words
A compound of the formula ##STR33## wherein X and Y are each selected from the group consisting of hydrogen, 5-fluoro, 6-fluoro, 5-chloro, 6-chloro, 5-trifluoromethyl and 6-trifluoromethyl, provided that X and Y are not both hydrogen; and R 2 is selected from the group consisting of alkyl having from 1 to 6 carbons, cycloalkyl having from 3 to 7 carbons, benzyl, furyl, thienyl, pyridyl and a group of the formula ##STR34## wherein R 3 and R 4 are each selected from the group consisting of hydrogen, fluoro, chloro, alkyl having 1 to 4 carbons, alkoxy having 1 to 4 carbons and trifluoromethyl.
Claim 57
Dependent Claim
10 words
A compound according to claim 50, wherein Y is hydrogen.
Claim 58
Dependent Claim
19 words
A compound according to claim 51, wherein R 2 is selected from the group consisting of isopropyl and t-butyl.
Claim 59
Dependent Claim
12 words
A compound according to claim 52, wherein X is 5-chloro or 6-chloro.
Claim 60
Dependent Claim
15 words
The compound according to claim 53, wherein X is 5-chloro and R 2 is t-butyl.
Claim 61
Dependent Claim
15 words
The compound according to claim 53, wherein X is 6-chloro and R 2 is t-butyl.
Claim 62
Dependent Claim
10 words
A compound according to claim 52, wherein X is 5-fluoro.
Claim 63
Dependent Claim
11 words
The compound according to claim 56, wherein R 2 is t-butyl.
References Cited (Backward Citations)
US3190889A
Cited
US3462450A
Cited
GB1158532A
Cited
US3519592A
Cited
US3631177A
Cited
GB1206995A
Cited
US3856967A
Cited
US3634453A
Cited
US3749731A
Cited
US4012394A
Cited
US3975531A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1989-02-10 | 1989-08-12 | 1990-02-11 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1993-02-10 | 1993-08-12 | 1994-02-11 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1997-02-10 | 1997-08-12 | 1998-02-11 | $7700.00 | Window Closed / Lapsed |