Patent US4708966A successfully refreshed from Google Patents.
US4708966A
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Novel anti-inflammatory agents, pharmaceutical compositions and methods for reducing inflammation
Assignee: Procter and Gamble Co
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Filing: 1986-06-27
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Granted: 1987-11-24
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Expires: 2006-06-27
Abstract
Abstract The present invention relates to novel specifically-substituted phenyl compounds, especially substituted di-tert-butyl phenol derivatives, which are effective as anti-inflammatory, analgesic and/or antipyretic agents. These phenyl compounds are substituted with a low molecular weight alkyl chain which terminates in a specific unsaturated functional group. These unsaturated functionalities are --C.tbd.CH, C═CH 2 , C═C═CH 2 , and aldehydes in the form of their acetals. The present invention further relates to pharmaceutical compositions which contain an anti-inflammatory agent of the present invention and a pharmaceutically-acceptable carrier. Finally, the present invention relates to methods for treating diseases characterized by inflammation, such as rheumatoid arthritis and osteoarthritis, in humans or lower animals. Such methods comprise administering to a human or lower animal in need of such treatment a safe and effective amount of an anti-inflammatory agent or composition of the present invention.
Inventors
- 👤 Maurice E. Loomans
- 👤 Randall S. Matthews
- 👤 Joseph A. Miller
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-05 17:15
CPC Classifications
C; C07; C07C; C07C15/00; C07C15/40; C07C15/42; C07C15/48; C07C49/00; C07C49/76; C07C49/84; A; A61; A61K; A61K31/00; A61K31/01; A61P; A61P25/00; A61P25/04; A61P29/00; A61P3/00; A61P3/06; A61P37/00; A61P43/00; A61P9/00; A61P9/10; C07C39/00; C07C39/18; C07C43/00; C07C43/30; C07C43/315; C07C45/00; C07C45/004; C07C45/27; C07C45/29; C07C45/292; C07C45/45; C07C45/61; C07C45/67; C07C45/673; C07C45/68; C07C45/70; C07C45/71; C07C49/20; C07C49/24; C07C49/245; C07C49/248; C07C49/255; C07C49/794; C07C49/80; C07C49/82; C07C49/835; C07F; C07F7/00; C07F7/02; C07F7/08; C07F7/0803; C07F7/081
Claims Analysis
Total Claims: 27
Claim 1
Independent Claim
549 words
An anti-inflammatory compound having the structure: ##STR33## wherein: (a) A 1 is selected from the group consisting of --OH, --H, and --O 2 CR; wherein R is a straight or branched chain alkyl group having from 1 to about 10 carbon atoms; (b) A 2 and A 3 are independently selected from the group consisting of --C(CH 3 ) 3 , --Si(CH 3 ) 3 , and --CF 3 ; and (c) Y is selected from the group consisting of: (1) --(CR 1 2 ) n --C.tbd.C--H, wherein n is an integer from 1 to about 6; (2) ##STR34## wherein n is an integer from 0 to about 5; (3) ##STR35## wherein m is an integer from 1 to about 5, and m+n is an integer from 1 to about 5; (4) ##STR36## wherein n is 0 or 1; (5) --(CR 1 2 ) n --CR 3 ═CH 2 , wherein n is an integer from about 2 to about 6; (6) ##STR37## wherein n is an integer from 0 to about 5; (7) ##STR38## wherein m is an integer from 1 to about 3, and m+n is an integer from 1 to about 3; (8) ##STR39## wherein n is an integer from 0 to about 3; (9) --(CR 1 2 ) n --CR 3 ═C═CH 2 , wherein n is an integer from 0 to about 6; (10) ##STR40## wherein m+n is an integer from 0 to about 5; (11) ##STR41## wherein n is an integer from 0 to about 3; (12) --(CR 1 2 ) n --CH(ZR 4 ) 2 , wherein n is an integer from 1 to about 6; and (13) ##STR42## wherein n is an integer from 1 to about 5, m is an integer from 0 to about 4, and m+n is an integer from about 1 to about 5; and wherein each R 1 is independently selected from the group consisting of --H, --OR 3 , --NR 3 2 , --NR 3 3 + , --N(R 3 )C(O)R 3 , --O 2 CR 3 , --CO 2 R 3 , C(O)NR 3 2 , straight or branched chain saturated alkyl group having from 1 to about 3 carbon atoms, and straight or branched chain unsaturated alkyl group having from 1 to about 3 carbon atoms; each R 2 is independently selected from the group consisting of --H, --OR 3 , --NR 3 2 , --NR 3 3 + , --N(R 3 )C(O)R 3 , --O 2 CR 3 , --CO 2 R 3 , C(O)NR 3 2 , straight or branched chain saturated alkyl group having from 1 to about 3 carbon atoms, and straight or branched chain unsaturated alkyl group having from 1 to about 2 carbon atoms; each R 3 is independently selected from the group consisting of --H, methyl and ethyl; each R 4 is independently selected from the group consisting of --CH 3 and --CH 2 CH 3 , or the R 4 's may be joined to form a cyclic acetal such that both R 4 's together are one group selected from --(CH 2 ) 2 -- and --(CH 2 ) 3 --; and each Z is independently selected from the group consisting of O, S, NH, and NR 4 ; or the pharmaceutically-acceptable salt thereof.
Claim 2
Dependent Claim
549 words
An anti-inflammatory compound having the structure: ##STR33## wherein: (a) A 1 is selected from the group consisting of --OH, --H, and --O 2 CR; wherein R is a straight or branched chain alkyl group having from 1 to about 10 carbon atoms; (b) A 2 and A 3 are independently selected from the group consisting of --C(CH 3 ) 3 , --Si(CH 3 ) 3 , and --CF 3 ; and (c) Y is selected from the group consisting of: (1) --(CR 1 2 ) n --C.tbd.C--H, wherein n is an integer from 1 to about 6; (2) ##STR34## wherein n is an integer from 0 to about 5; (3) ##STR35## wherein m is an integer from 1 to about 5, and m+n is an integer from 1 to about 5; (4) ##STR36## wherein n is 0 or 1; (5) --(CR 1 2 ) n --CR 3 ═CH 2 , wherein n is an integer from about 2 to about 6; (6) ##STR37## wherein n is an integer from 0 to about 5; (7) ##STR38## wherein m is an integer from 1 to about 3, and m+n is an integer from 1 to about 3; (8) ##STR39## wherein n is an integer from 0 to about 3; (9) --(CR 1 2 ) n --CR 3 ═C═CH 2 , wherein n is an integer from 0 to about 6; (10) ##STR40## wherein m+n is an integer from 0 to about 5; (11) ##STR41## wherein n is an integer from 0 to about 3; (12) --(CR 1 2 ) n --CH(ZR 4 ) 2 , wherein n is an integer from 1 to about 6; and (13) ##STR42## wherein n is an integer from 1 to about 5, m is an integer from 0 to about 4, and m+n is an integer from about 1 to about 5; and wherein each R 1 is independently selected from the group consisting of --H, --OR 3 , --NR 3 2 , --NR 3 3 + , --N(R 3 )C(O)R 3 , --O 2 CR 3 , --CO 2 R 3 , C(O)NR 3 2 , straight or branched chain saturated alkyl group having from 1 to about 3 carbon atoms, and straight or branched chain unsaturated alkyl group having from 1 to about 3 carbon atoms; each R 2 is independently selected from the group consisting of --H, --OR 3 , --NR 3 2 , --NR 3 3 + , --N(R 3 )C(O)R 3 , --O 2 CR 3 , --CO 2 R 3 , C(O)NR 3 2 , straight or branched chain saturated alkyl group having from 1 to about 3 carbon atoms, and straight or branched chain unsaturated alkyl group having from 1 to about 2 carbon atoms; each R 3 is independently selected from the group consisting of --H, methyl and ethyl; each R 4 is independently selected from the group consisting of --CH 3 and --CH 2 CH 3 , or the R 4 's may be joined to form a cyclic acetal such that both R 4 's together are one group selected from --(CH 2 ) 2 -- and --(CH 2 ) 3 --; and each Z is independently selected from the group consisting of O, S, NH, and NR 4 ; or the pharmaceutically-acceptable salt thereof.
Claim 3
Dependent Claim
44 words
An anti-inflammatory compound according to claim 1 wherein A 1 is OH or H; and both A 2 and A 3 are the same group selected from the group consisting of --C(CH 3 ) 3 , --Si(CH 3 ) 3 and --CF 3 .
Claim 4
Dependent Claim
11 words
An anti-inflammatory compound according to claim 2 having the structure: ##STR43##
Claim 5
Dependent Claim
97 words
An anti-inflammatory compound according to claim 3 wherein: (a) each R 1 and R 2 is independently selected from the group consisting of --H, --OH, ═CH 2 , methyl, or ethyl; and wherein further no more than about two R 1 or R 2 groups are a group other than --H; (b) each R 3 is --H; (c) each R 4 is methyl, or both R 4 groups together are the group --(CH 2 ) 2 -- which forms a cyclic acetal; and (d) each Z is independently selected from the group consisting of O or S.
Claim 6
Dependent Claim
113 words
An anti-inflammatory compound according to claim 4 wherein the Y group is selected from the group consisting of: (1) --(CR 1 2 ) n --C.tbd.CH, wherein n is an integer from 1 to about 6; (2) ##STR44## wherein n is an integer from 0 to about 5; (3) ##STR45## wherein n is an integer from 0 to about 3; (4) ##STR46## wherein n is 0 or 1; (5) --(CR 1 2 ) n --CH(ZR 4 ) 2 , wherein n is an integer from 1 to about 6; (6) ##STR47## wherein n is an integer from 1 to about 5; and (7) ##STR48## wherein n is an integer from 1 to about 3.
Claim 7
Dependent Claim
55 words
An anti-inflammatory compound according to claim 5 wherein the Y group is selected from the group consisting of (1) ##STR49## wherein n is an integer from 0 to about 3; (2) ##STR50## wherein n is an integer from 1 to about 5; and, (3) ##STR51## wherein n is an integer from 0 to about 5.
Claim 8
Dependent Claim
22 words
An anti-inflammatory compound according to claim 3 having the general formula: ##STR52## wherein n is an integer from 0 to about 5.
Claim 9
Dependent Claim
44 words
An anti-inflammatory compound according to claim 7 wherein each R 2 is independently selected from the group consisting of --H, --OH, ═CH 2 , methyl, or ethyl; and wherein further no more than about two R 2 groups are a group other than --H.
Claim 10
Dependent Claim
12 words
An anti-inflammatory compound according to claim 7 wherein R 2 is hydrogen.
Claim 11
Dependent Claim
53 words
An anti-inflammatory compound selected from the group of compounds consisting of: 4-propynoyl-2,6-di-t-butylphenol; 4-(1'-hydroxy-2'-propynyl)-2,6-di-t-butylphenol; 4-(3'-butynoyl)-2,6-di-t-butylphenol; 4-butadienoyl-2,6-di-t-butylphenol; 4-(4'-pentynoyl)-2,6-di-t-butylphenol; 4-(4'-pentenoyl)-2,6-di-t-butylphenol; 4-(2'-dimethoxymethyl-4'-pentynoyl)-2,6-di-t-butylphenol; 4-(2',2'-dimethyl-4'-pentynoyl)-2,6-di-t-butylphenol; 4-(3',3'-dimethyl-4'-pentynoyl)-2,6-di-t-butylphenol; 4-(4'-pentyn-3'-one)-2,6-di-t-butylphenol; 4-(5'-hexynoyl)-2,6-di-t-butylphenol; 4-(5'-hexenoyl)-2,6-di-t-butylphenol; 4-(2'-methyl-5'-hexynoyl)-2,6-di-t-butylphenol; 4-(1'-hydroxy-5'-hexynyl)-2,6-di-t-butylphenol; 4-(5'-hexynyl)-2,6-di-t-butylphenol; 4-(1'-methylidene-5'-hexynyl)-2,6-di-t-butylphenol; 4-((S)-(-)-3'-methyl-5'-hexynoyl)-2,6-di-t-butylphenol; 4-((R)-(+)-3'-methyl-5'-hexynoyl)-2,6-di-t-butylphenol; 1-(5'-hexynoyl)-3,5-di-t-butylbenzene; 4-(5'-hexynoyl)-2,6-bis-trimethylsilylphenol; 1-(5'-hexynoyl)-3,5-bis-trimethylsilylbenzene; 1-(5'-hexynoyl)-3,5-bis(trifluoromethyl)benzene; 4-(6'-heptynoyl)-2,6-di-t-butylphenol; 4-(6'-heptyn-340 -one)-2,6-di-t-butylphenol; 4-(4'-(2"-propynyl)-6'-heptyn-3'-one)-2,6-di-t-butylphenol; 4-(7'-octynoyl)-2,6-di-t-butylphenol; 4-((E)-1'-penten-4'-yn-3'-one)-2,6-di-t-butylphenol; 4-((E)-1',6'-heptadiene-3'-one)-2,6-di-t-butylphenol; 4-(3',3'-dimethoxypropionyl)-2,6-di-t-butylphenol; 4-(2'-(1",3"-dioxolane)acetyl)-2,6-di-t-butylphenol; 4-(3',3'-diethoxypropionyl)-2,6-di-t-butylphenol; 4-(2'-(1",3"-oxathiolane)acetyl)-2,6-di-t-butylphenol; 4-(2',2'-dimethoxyethyl)-2,6-di-t-butylphenol; 4-(5',5'-dimethoxy-3'-pentanone)-2,6-di-t-butylphenol; and 4-(3',3'-dimethyl-5'-hexynoyl)-2,6-di-t-butylphenol, or the pharmaceutically-acceptable salt thereof.
Claim 12
Dependent Claim
53 words
An anti-inflammatory compound selected from the group of compounds consisting of: 4-propynoyl-2,6-di-t-butylphenol; 4-(1'-hydroxy-2'-propynyl)-2,6-di-t-butylphenol; 4-(3'-butynoyl)-2,6-di-t-butylphenol; 4-butadienoyl-2,6-di-t-butylphenol; 4-(4'-pentynoyl)-2,6-di-t-butylphenol; 4-(4'-pentenoyl)-2,6-di-t-butylphenol; 4-(2'-dimethoxymethyl-4'-pentynoyl)-2,6-di-t-butylphenol; 4-(2',2'-dimethyl-4'-pentynoyl)-2,6-di-t-butylphenol; 4-(3',3'-dimethyl-4'-pentynoyl)-2,6-di-t-butylphenol; 4-(4'-pentyn-3'-one)-2,6-di-t-butylphenol; 4-(5'-hexynoyl)-2,6-di-t-butylphenol; 4-(5'-hexenoyl)-2,6-di-t-butylphenol; 4-(2'-methyl-5'-hexynoyl)-2,6-di-t-butylphenol; 4-(1'-hydroxy-5'-hexynyl)-2,6-di-t-butylphenol; 4-(5'-hexynyl)-2,6-di-t-butylphenol; 4-(1'-methylidene-5'-hexynyl)-2,6-di-t-butylphenol; 4-((S)-(-)-3'-methyl-5'-hexynoyl)-2,6-di-t-butylphenol; 4-((R)-(+)-3'-methyl-5'-hexynoyl)-2,6-di-t-butylphenol; 1-(5'-hexynoyl)-3,5-di-t-butylbenzene; 4-(5'-hexynoyl)-2,6-bis-trimethylsilylphenol; 1-(5'-hexynoyl)-3,5-bis-trimethylsilylbenzene; 1-(5'-hexynoyl)-3,5-bis(trifluoromethyl)benzene; 4-(6'-heptynoyl)-2,6-di-t-butylphenol; 4-(6'-heptyn-340 -one)-2,6-di-t-butylphenol; 4-(4'-(2"-propynyl)-6'-heptyn-3'-one)-2,6-di-t-butylphenol; 4-(7'-octynoyl)-2,6-di-t-butylphenol; 4-((E)-1'-penten-4'-yn-3'-one)-2,6-di-t-butylphenol; 4-((E)-1',6'-heptadiene-3'-one)-2,6-di-t-butylphenol; 4-(3',3'-dimethoxypropionyl)-2,6-di-t-butylphenol; 4-(2'-(1",3"-dioxolane)acetyl)-2,6-di-t-butylphenol; 4-(3',3'-diethoxypropionyl)-2,6-di-t-butylphenol; 4-(2'-(1",3"-oxathiolane)acetyl)-2,6-di-t-butylphenol; 4-(2',2'-dimethoxyethyl)-2,6-di-t-butylphenol; 4-(5',5'-dimethoxy-3'-pentanone)-2,6-di-t-butylphenol; and 4-(3',3'-dimethyl-5'-hexynoyl)-2,6-di-t-butylphenol, or the pharmaceutically-acceptable salt thereof.
Claim 13
Dependent Claim
21 words
An anti-inflammatory compound according to claim 10 selected from the group of compounds consisting of: 4-(4'-pentyn-3'-one)-2,6-di-t-butylphenol; 4-(5'-hexynoyl)-2,6-di-t-butylphenol; 4-((S)-(-)-3'-methyl-5'-hexynoyl)-2,6-di-t-butylphenol; 4-((R)-(+)-3'-methyl-5'-hexynoyl)-2,6-di-t-butylphenol; and 4-(3',3'-dimethoxypropionyl)-2,6-di-t-butylphenol.
Claim 14
Dependent Claim
9 words
The anti-inflammatory compound 4-(5'-hexynoyl)-2,6-di-t-butylphenol, or the pharmaceutically-acceptable salt thereof.
Claim 15
Dependent Claim
9 words
The anti-inflammatory compound 4-(5'-hexynoyl)-2,6-di-t-butylphenol, or the pharmaceutically-acceptable salt thereof.
Claim 16
Dependent Claim
23 words
A pharmaceutical composition comprising: (a) a safe and effective amount of an anti-inflammatory compound according to claim 1; and (b) a pharmaceutically-acceptable carrier.
Claim 17
Dependent Claim
23 words
A pharmaceutical composition comprising: (a) a safe and effective amount of an anti-inflammatory compound according to claim 3; and (b) a pharmaceutically-acceptable carrier.
Claim 18
Dependent Claim
23 words
A pharmaceutical composition comprising: (a) a safe and effective amount of an anti-inflammatory compound according to claim 6; and (b) a pharmaceutically-acceptable carrier.
Claim 19
Dependent Claim
23 words
A pharmaceutical composition comprising: (a) a safe and effective amount of an anti-inflammatory compound according to claim 7; and (b) a pharmaceutically-acceptable carrier.
Claim 20
Dependent Claim
23 words
A pharmaceutical composition comprising: (a) a safe and effective amount of an anti-inflammatory compound according to claim 9; and (b) a pharmaceutically-acceptable carrier.
Claim 21
Dependent Claim
23 words
A pharmaceutical composition comprising: (a) a safe and effective amount of an anti-inflammatory compound according to claim 11; and (b) a pharmaceutically-acceptable carrier.
Claim 22
Dependent Claim
23 words
A pharmaceutical composition comprising: (a) a safe and effective amount of an anti-inflammatory compound according to claim 12; and (b) a pharmaceutically-acceptable carrier.
Claim 23
Dependent Claim
35 words
A method for treating diseases characterized by inflammation, said method comprising administering to a human or lower animal in need of such treatment a safe and effective amount of an anti-inflammatory compound of claim 1.
Claim 24
Dependent Claim
35 words
A method for treating diseases characterized by inflammation, said method comprising administering to a human or lower animal in need of such treatment a safe and effective amount of an anti-inflammatory compound of claim 7.
Claim 25
Dependent Claim
35 words
A method for treating diseases characterized by inflammation, said method comprising administering to a human or lower animal in need of such treatment a safe and effective amount of an anti-inflammatory compound of claim 9.
Claim 26
Dependent Claim
35 words
A method for treating diseases characterized by inflammation, said method comprising administering to a human or lower animal in need of such treatment a safe and effective amount of an anti-inflammatory compound of claim 11.
Claim 27
Dependent Claim
35 words
A method for treating diseases characterized by inflammation, said method comprising administering to a human or lower animal in need of such treatment a safe and effective amount of an anti-inflammatory compound of claim 12.
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