US5543534A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Acetylenes disubstituted with a 5 substituted tetrahydronaphthyl group and with an aryl or heteroaryl groups having retinoid-like biological activity
Assignee: Allergan Inc
•
Filing: 1994-12-29
•
Granted: 1996-08-06
•
Expires: 2014-12-29
Abstract
Abstract Compounds of Formula 1 ##STR1## wherein X is S or O; R 1 -R 5 , m, o, X, Y, A, B are as defined in the specification.
Inventors
- 👤 Vidyasagar Vuligonda
- 👤 Min Teng
- 👤 Richard L. Beard
- 👤 Alan T. Johnson
- 👤 Yuan Lin
- 👤 Roshantha A. Chandraratna
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-30 19:55
CPC Classifications
C; C07; C07D; C07D213/00; C07D213/02; C07D213/04; C07D213/60; C07D213/78; C07D213/79; C07D213/80; C07C; C07C17/00; C07C17/093; C07C17/10; C07C17/26; C07C17/263; C07C17/35; C07C229/00; C07C229/46; C07C233/00; C07C233/57; C07C233/58; C07C251/00; C07C251/32; C07C251/34; C07C251/48; C07C255/00; C07C255/01; C07C255/32; C07C255/41; C07C255/45; C07C255/47; C07C309/00; C07C309/63; C07C309/64; C07C309/65; C07C323/00; C07C323/50; C07C323/61; C07C327/00; C07C327/20; C07C327/32; C07C45/00; C07C45/27; C07C45/28; C07C45/61; C07C45/67; C07C45/673; C07C63/00; C07C63/66; C07C65/00; C07C65/01; C07C65/19; C07C65/21; C07C65/28; C07C65/32; C07C65/38; C07C69/00; C07C69/76; C07D213/24; C07D213/54; C07D213/55; C07D277/00; C07D277/02; C07D277/20; C07D277/22; C07D277/30; C07D307/00; C07D307/02; C07D307/34; C07D307/38; C07D307/54; C07D309/00; C07D309/02; C07D309/04; C07D309/06; C07D309/08; C07D309/10; C07D309/12; C07D333/00; C07D333/02; C07D333/04; C07D333/06; C07D333/24; C07D339/00; C07D339/08; C07F; C07F7/00; C07F7/02; C07F7/08; C07F7/0803; C07F7/081; C07F7/18; C07F7/1804; C07C2602/00; C07C2602/02; C07C2602/04; C07C2602/10
Claims Analysis
Total Claims: 26
Claim 1
Independent Claim
486 words
A compound of the formula ##STR10## wherein X is S or O; R 1 is hydrogen or alkyl of 1 to 10 carbons; R 2 and R 3 are hydrogen, or alkyl of 1 to 6 carbons and the substituted ethynyl group occupies either the 2 or the 3 position of the tetrahydronaphthalene nucleus; m is an integer having the value of 0-3; o is an integer having the value 0-4; R 4 is hydrogen, alkyl of 1 to 10 carbons, alkenyl of 2 to 10 carbons and having 1 to 3 double bonds, alkynyl having 2 to 10 carbons and 1 to 3 triple bonds, carbocyclic aryl selected from the group consisting of phenyl, C 1 -C 10 -alkylphenyl, naphthyl, C 1 -C 10 -alkylnaphthyl, phenyl-C 1 -C 10 alkyl, napthyl-C 1 -C 10 alkyl; CN, or (CH 2 ) p CO 2 R 8 where p is an integer between 0 to 10; R 5 is C(R 15 )(R 16 )XR 17 ; Y is a phenyl group optionally substituted with one or two R 2 groups; A is (CH 2 ) n where n is 0-5, lower branched chain alkyl having 3-6 carbons, cycloalkyl having 3-6 carbons, alkenyl having 2-6 carbons and 1 or 2 double bonds, alkynyl having 2-6 carbons and 1 or 2 triple bonds, and B is hydrogen, COOH or a pharmaceutically acceptable salt thereof, COOR 8 , CONR 9 R 10 , --CH 2 OH, CH 2 OR 11 , CH 2 OCOR 11 , CHO, CH(OR 12 ) 2 , CHOR 13 O, --COR 7 , CR 7 (OR 12 ) 2 , CR 7 OR 13 O, or tri-lower alkylsilyl, where R 7 is an alkyl, cycloalkyl or alkenyl group containing 1 to 5 carbons, R 8 is an alkyl group of 1 to 10 carbons, a cycloalkyl group of 5 to 10 carbons or trimethylsilylalkyl where the alkyl group has 1 to 10 carbons, or R 8 is phenyl or lower alkylphenyl, R 9 and R 10 independently are hydrogen, an alkyl group of 1 to 10 carbons, or a cycloalkyl group of 5-10 carbons, or phenyl or lower alkylphenyl, R 11 is lower alkyl, phenyl or lower alkylphenyl, R 12 is lower alkyl, and R 13 is divalent alkyl radical of 2-5 carbons; and further wherein R 14 is hydrogen, alkyl of 1 to 10 carbons, alkenyl of 2 to 10 carbons and having 1 to 3 double bond, alkynyl having 2 to 10 carbons and 1 to 3 triple bonds, carbocyclic aryl selected from the group consisting of phenyl, C 1 -C 10 -alkylphenyl, naphthyl, C 1 -C 10 -alkylnaphthyl, phenyl-C 1 -C 10 alkyl, napthyl-C 1 -C 10 alkyl; R 15 is hydrogen or lower alkyl of 1 to 6 carbons and R 16 and R 17 jointly form a ring having a total of 4 to 5 carbons and the X heteroatom.
Claim 2
Dependent Claim
486 words
A compound of the formula ##STR10## wherein X is S or O; R 1 is hydrogen or alkyl of 1 to 10 carbons; R 2 and R 3 are hydrogen, or alkyl of 1 to 6 carbons and the substituted ethynyl group occupies either the 2 or the 3 position of the tetrahydronaphthalene nucleus; m is an integer having the value of 0-3; o is an integer having the value 0-4; R 4 is hydrogen, alkyl of 1 to 10 carbons, alkenyl of 2 to 10 carbons and having 1 to 3 double bonds, alkynyl having 2 to 10 carbons and 1 to 3 triple bonds, carbocyclic aryl selected from the group consisting of phenyl, C 1 -C 10 -alkylphenyl, naphthyl, C 1 -C 10 -alkylnaphthyl, phenyl-C 1 -C 10 alkyl, napthyl-C 1 -C 10 alkyl; CN, or (CH 2 ) p CO 2 R 8 where p is an integer between 0 to 10; R 5 is C(R 15 )(R 16 )XR 17 ; Y is a phenyl group optionally substituted with one or two R 2 groups; A is (CH 2 ) n where n is 0-5, lower branched chain alkyl having 3-6 carbons, cycloalkyl having 3-6 carbons, alkenyl having 2-6 carbons and 1 or 2 double bonds, alkynyl having 2-6 carbons and 1 or 2 triple bonds, and B is hydrogen, COOH or a pharmaceutically acceptable salt thereof, COOR 8 , CONR 9 R 10 , --CH 2 OH, CH 2 OR 11 , CH 2 OCOR 11 , CHO, CH(OR 12 ) 2 , CHOR 13 O, --COR 7 , CR 7 (OR 12 ) 2 , CR 7 OR 13 O, or tri-lower alkylsilyl, where R 7 is an alkyl, cycloalkyl or alkenyl group containing 1 to 5 carbons, R 8 is an alkyl group of 1 to 10 carbons, a cycloalkyl group of 5 to 10 carbons or trimethylsilylalkyl where the alkyl group has 1 to 10 carbons, or R 8 is phenyl or lower alkylphenyl, R 9 and R 10 independently are hydrogen, an alkyl group of 1 to 10 carbons, or a cycloalkyl group of 5-10 carbons, or phenyl or lower alkylphenyl, R 11 is lower alkyl, phenyl or lower alkylphenyl, R 12 is lower alkyl, and R 13 is divalent alkyl radical of 2-5 carbons; and further wherein R 14 is hydrogen, alkyl of 1 to 10 carbons, alkenyl of 2 to 10 carbons and having 1 to 3 double bond, alkynyl having 2 to 10 carbons and 1 to 3 triple bonds, carbocyclic aryl selected from the group consisting of phenyl, C 1 -C 10 -alkylphenyl, naphthyl, C 1 -C 10 -alkylnaphthyl, phenyl-C 1 -C 10 alkyl, napthyl-C 1 -C 10 alkyl; R 15 is hydrogen or lower alkyl of 1 to 6 carbons and R 16 and R 17 jointly form a ring having a total of 4 to 5 carbons and the X heteroatom.
Claim 3
Dependent Claim
13 words
A compound of claim 1 where the phenyl ring is 1,4 (para) substituted.
Claim 4
Dependent Claim
10 words
A compound of claim 1 where R 2 is hydrogen.
Claim 5
Dependent Claim
10 words
A compound of claim 1 where R 3 is hydrogen.
Claim 6
Dependent Claim
17 words
A compound of claim 1 where R 4 is hydrogen, CN, or CH 2 COOR 8 .
Claim 7
Dependent Claim
10 words
A compound of claim 1 where R 5 is tetrahydropyranyl.
Claim 8
Dependent Claim
9 words
A compound of claim 1 where X is O.
Claim 9
Dependent Claim
9 words
A compound of claim 1 where X is S.
Claim 10
Dependent Claim
328 words
A compound of the formula ##STR11## wherein X is S or O; R 1 is hydrogen or alkyl of 1 to 10 carbons; R 2 and R 3 are hydrogen, or alkyl of 1 to 6 carbons and the substituted ethynyl group occupies either the 2 or the 3 position of the tetrahydronaphthalene nucleus; m is an integer having the value of 0-3; o is an integer having the value 0-4; R 4 is hydrogen, alkyl of 1 to 10 carbons, CN, or CH 2 CO 2 R 8 ; R 5 is 2-tetrahydropyranyl or 2-tetrahydrothiopyranyl; Y is phenyl optionally substituted with one or two R 2 groups; A is (CH 2 ) n where n is 0-5, lower branched chain alkyl having 3-6 carbons, cycloalkyl having 3-6 carbons, alkenyl having 2-6 carbons and 1 or 2 double bonds, alkynyl having 2-6 carbons and 1 or 2 triple bonds, and B is hydrogen, COOH or a pharmaceutically acceptable salt thereof, COOR 8 , CONR 9 R 10 , --CH 2 OH, CH 2 OR 11 , CH 2 OCOR 11 , CHO, CH(OR 12 ) 2 , CHOR 13 O, --COR 7 , CR 7 (OR 12 ) 2 , CR 7 OR 13 O, or tri-lower alkylsilyl, where R 7 is an alkyl, cycloalkyl or alkenyl group containing 1 to 5 carbons, R 8 is an alkyl group of 1 to 10 carbons, a cycloalkyl group of 5 to 10 carbons or trimethylsilylalkyl where the alkyl group has 1 to 10 carbons, or R 8 is phenyl or lower alkylphenyl, R 9 and R 10 independently are hydrogen, an alkyl group of 1 to 10 carbons, or a cycloalkyl group of 5-10 carbons, or phenyl or lower alkylphenyl, R 11 is lower alkyl, phenyl or lower alkylphenyl, R 12 is lower alkyl, and R 13 is divalent alkyl radical of 2-5 carbons; and further wherein R 14 is hydrogen, alkyl of 1 to 10 carbons or phenyl.
Claim 11
Dependent Claim
328 words
A compound of the formula ##STR11## wherein X is S or O; R 1 is hydrogen or alkyl of 1 to 10 carbons; R 2 and R 3 are hydrogen, or alkyl of 1 to 6 carbons and the substituted ethynyl group occupies either the 2 or the 3 position of the tetrahydronaphthalene nucleus; m is an integer having the value of 0-3; o is an integer having the value 0-4; R 4 is hydrogen, alkyl of 1 to 10 carbons, CN, or CH 2 CO 2 R 8 ; R 5 is 2-tetrahydropyranyl or 2-tetrahydrothiopyranyl; Y is phenyl optionally substituted with one or two R 2 groups; A is (CH 2 ) n where n is 0-5, lower branched chain alkyl having 3-6 carbons, cycloalkyl having 3-6 carbons, alkenyl having 2-6 carbons and 1 or 2 double bonds, alkynyl having 2-6 carbons and 1 or 2 triple bonds, and B is hydrogen, COOH or a pharmaceutically acceptable salt thereof, COOR 8 , CONR 9 R 10 , --CH 2 OH, CH 2 OR 11 , CH 2 OCOR 11 , CHO, CH(OR 12 ) 2 , CHOR 13 O, --COR 7 , CR 7 (OR 12 ) 2 , CR 7 OR 13 O, or tri-lower alkylsilyl, where R 7 is an alkyl, cycloalkyl or alkenyl group containing 1 to 5 carbons, R 8 is an alkyl group of 1 to 10 carbons, a cycloalkyl group of 5 to 10 carbons or trimethylsilylalkyl where the alkyl group has 1 to 10 carbons, or R 8 is phenyl or lower alkylphenyl, R 9 and R 10 independently are hydrogen, an alkyl group of 1 to 10 carbons, or a cycloalkyl group of 5-10 carbons, or phenyl or lower alkylphenyl, R 11 is lower alkyl, phenyl or lower alkylphenyl, R 12 is lower alkyl, and R 13 is divalent alkyl radical of 2-5 carbons; and further wherein R 14 is hydrogen, alkyl of 1 to 10 carbons or phenyl.
Claim 12
Dependent Claim
9 words
A compound of claim 9 where X is O.
Claim 13
Dependent Claim
36 words
A compound of claim 10 where A is (CH 2 ) n where n is 0-5 and where B is COOH or a pharmaceutically acceptable salt thereof, COOR 8 , or CONR 9 R 10 .
Claim 14
Dependent Claim
9 words
A compound of claim 9 where X is S.
Claim 15
Dependent Claim
36 words
A compound of claim 12 where A is (CH 2 ) n where n is 0-5 and where B is COOH or a pharmaceutically acceptable salt thereof, COOR 8 , or CONR 9 R 10 .
Claim 16
Dependent Claim
80 words
A compound of the formula ##STR12## wherein X is S or O; X 2 is CH; R 4 is hydrogen, alkyl of 1 to 10 carbons, CN, or (CH 2 )CO 2 R 8 ; R 5 is 2-tetrahydropyranyl or 2-tetrahydrothiopyranyl, the substituted ethynyl group occupies either the 2 or 3 position of the tetrahydronaphthalene nucleus, and R 8 is hydrogen, an alkyl group of 1 to 10 carbons or trimethylsilylalkyl where the alkyl group has 1 to 10 carbons.
Claim 17
Dependent Claim
80 words
A compound of the formula ##STR12## wherein X is S or O; X 2 is CH; R 4 is hydrogen, alkyl of 1 to 10 carbons, CN, or (CH 2 )CO 2 R 8 ; R 5 is 2-tetrahydropyranyl or 2-tetrahydrothiopyranyl, the substituted ethynyl group occupies either the 2 or 3 position of the tetrahydronaphthalene nucleus, and R 8 is hydrogen, an alkyl group of 1 to 10 carbons or trimethylsilylalkyl where the alkyl group has 1 to 10 carbons.
Claim 18
Dependent Claim
9 words
A compound of claim 14 where X is O.
Claim 19
Dependent Claim
10 words
A compound of claim 15 where R 4 is H.
Claim 20
Dependent Claim
10 words
A compound of claim 16 where R 5 is 2-tetrahydropyranyl.
Claim 21
Dependent Claim
16 words
A compound of claim 17 where R 8 is H or C 2 H 5 .
Claim 22
Dependent Claim
10 words
A compound of claim 15 where R 4 is CN.
Claim 23
Dependent Claim
9 words
A compound of claim 14 where X is S.
Claim 24
Dependent Claim
10 words
A compound of claim 20 where R 4 is H.
Claim 25
Dependent Claim
10 words
A compound of claim 21 where R 5 is 2-tetrahydropyranyl.
Claim 26
Dependent Claim
16 words
A compound of claim 22 where R 8 is H or C 2 H 5 .
References Cited (Backward Citations)
US4096341A
Cited
US4326055A
Cited
US4391731A
Cited
DE3316932A1
Cited
EP0098591A1
Cited
EP0130795A2
Cited
WO1985000806A1
Cited
WO1985004652A1
Cited
US4826984A
Cited
US4695649A
Cited
DE3524199A1
Cited
EP0170105A2
Cited
US4723028A
Cited
US4740519A
Cited
EP0176034A2
Cited
EP0176032A2
Cited
EP0176033A2
Cited
US4826969A
Cited
DE3602473A1
Cited
DE3708060A1
Cited
US4855320A
Cited
GB2190378A
Cited
DE3715955A1
Cited
EP0253302A2
Cited
US4739098A
Cited
EP0272921A1
Cited
US4927947A
Cited
EP0284288A1
Cited
US5380877A
Cited
US5354752A
Cited
US5348972A
Cited
US5264578A
Cited
US5234926A
Cited
US4810804A
Cited
EP0303915A2
Cited
EP0315071A2
Cited
US5130335A
Cited
US5231113A
Cited
US4895868A
Cited
US5015658A
Cited
EP0350846A2
Cited
US5037825A
Cited
US5089509A
Cited
US4992468A
Cited
US5068252A
Cited
US5248777A
Cited
US5045551A
Cited
US4980369A
Cited
US5162546A
Cited
US5278318A
Cited
US5183827A
Cited
US5272156A
Cited
US5023341A
Cited
US5053523A
Cited
US5006550A
Cited
US5264456A
Cited
US5175185A
Cited
US5013744A
Cited
US5013744B1
Cited
US5349105A
Cited
US5202471A
Cited
WO1991016051A1
Cited
WO1992006948A1
Cited
US5346915A
Cited
US5346895A
Cited
US5348975A
Cited
US5324744A
Cited
US5134159A
Cited
US5326898A
Cited
US5391753A
Cited
US5324840A
Cited
US5344959A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1999-08-06 | 2000-02-05 | 2000-08-06 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2003-08-06 | 2004-02-05 | 2004-08-06 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2007-08-06 | 2008-02-05 | 2008-08-06 | $7700.00 | Window Closed / Lapsed |