US2002082419A1PendingUtilityA1
2,4-pentadienoic acid derivatives having retinoid-like biological activity
Est. expiryJun 6, 2015(expired)· nominal 20-yr term from priority
A61P 43/00C07C 57/50A61K 31/20C07C 69/618C07D 335/06C07D 311/58A61P 17/00A61K 31/23C07D 333/54
54
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Claims
Abstract
Compounds of Formula 1 wherein Z is selected from the group consisting of the radicals shown in Formula 2 and in Formula 3, Y is cycloalkyl or cycloalkenyl of 3 to 8 carbons optionally substituted with one or two R 4 groups, or Y is selected from phenyl, pyridyl, thienyl, furyl, pyrrolyl, pyridazinyl, pyrimidinyl, pyrazinyl, thiazolyl, oxazolyl, and imidazolyl, said groups being optionally substituted with one or two R 4 groups, the divalent Y radical being substituted by the Z and —CR 1 ═CR 1 —CR 1 ═CR 1 groups on adjacent carbons; X is S, O, or NR 5 ; n is 1 or 2; R 1 and R 2 independently are H, lower alkyl or fluoroalkyl; R 3 is hydrogen, lower alkyl, Cl or Br; R 4 is lower alkyl, fluoroalkyl or halogen; R 5 is H or lower alkyl, 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, have retinoid like biological activity.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1 . A compound of Formula 1
wherein Z is selected from the group consisting of the radicals shown in Formula 2 and in Formula 3,
Y is cycloalkyl or cycloalkenyl of 3 to 8 carbons optionally substituted with one or two R 4 groups, or Y is selected from phenyl, pyridyl, thienyl, furyl, pyrrolyl, pyridazinyl, pyrimidinyl, pyrazinyl, thiazolyl, oxazolyl, and imidazolyl, said groups being optionally substituted with one or two R 4 groups, the divalent Y radical being substituted by the Z and —CR 1 ═CR 1 —CR 1 ═CR 1 )— groups on adjacent carbons;
X is S, O, or NR 5 ;
n is 1 or 2;
R 1 and R 2 independently are H, lower alkyl or fluoroalkyl;
R 3 is hydrogen, lower alkyl, Cl or Br;
R 4 is lower alkyl, fluoroalkyl or halogen;
R 5 is H or lower alkyl, 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.
2 . A compound in accordance with claim 1 where Y is cyclopropyl.
3 . A compound in accordance with claim 1 where Y is phenyl.
4 . A compound in accordance with claim 1 where Y is selected from the group consisting of pyridyl, thienyl and furyl.
5 . A compound in accordance with claim 1 where Z is the radical shown in Formula 2.
6 . A compound in accordance with claim 1 where Z is the radical shown in Formula 3.
7 . A compound in accordance with claim 1 where B is COOH or a pharmaceutically acceptable salt thereof, COOR 8 , or CONR 9 R 10 .
8 . A compound in accordance with claim 1 where R 1 is H or methyl.
9 . A compound in accordance with claim 1 where s is the radical shown in Formula 2 and n is 2.
10 . A compound in accordance with claim 1 where S is the radical shown in Formula 3 and X is S or O.
11 . A compound of the formula
wherein R 2 is hydrogen or lower alkyl;
R 3 is hydrogen or lower alkyl, 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.
12 . A compound in accordance with claim 11 wherein R 2 is methyl.
13 . A compound in accordance with claim 12 wherein B is COOH or a pharmaceutically acceptable salt thereof, COOR 8 or CONR 9 R 10 .
14 . A compound in accordance with claim 13 where the cyclopropyl group is attached to the 2 position of the tetrahydronaphthalene nucleus.
15 . A compound in accordance with claim 14 where the configuration about the ▴ 4 double bond is trans.
16 . A compound in accordance with claim 15 where the B group represents COOH, COOCH 3 or COOC 2 H 5 , R 3 is attached to the 3 position of the tetrahydronaphthalene nucleus, configuration about the cyclopropane ring is trans and configuration about the 2 double bond is trans.
17 . A compound in accordance with claim 16 where B is COOH.
18 . A compound in accordance with claim 16 where B is COOC 2 H 5 .
19 . A compound in accordance with claim 15 where the B group represents COOH, COOCH 3 or COOC 2 H 5 , R 3 is attached to the 3 position of the tetrahydronaphthalene nucleus, configuration about the cyclopropane ring is trans and configuration about the ▴ 2 double bond is cis.
20 . A compound in accordance with claim 19 where B is COOH.
21 . A compound in accordance with claim 19 where B is COOC 2 H 5 .
22 . A compound in accordance with claim 15 where the B group represents COOH, COOCH 3 or COOC 2 H 5 , R 3 is attached to the 3 position of the tetrahydronaphthalene nucleus, configuration about the cyclopropane ring is cis and configuration about the ▴ 2 double bond is trans.
23 . A compound in accordance with claim 22 where B is COOH.
24 . A compound in accordance with claim 22 where B is COOC 2 H 5 .
25 . A compound in accordance with claim 15 where the B group represents COOH, COOCH 3 or COOC 2 H 5 , R 3 is attached to the 3 position of the tetrahydronaphthalene nucleus, configuration about the cyclopropane ring is cis and configuration about the ▴ 2 double bond is cis.
26 . A compound in accordance with claim 25 where B is COOH.
27 . A compound in accordance with claim 25 where B is COOC 2 H 5 .
28 . A compound of the formula
wherein R 2 is hydrogen or lower alkyl;
R 3 is hydrogen or lower alkyl, 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.
29 . A compound in accordance with claim 28 wherein R 2 is methyl.
30 . A compound in accordance with claim 29 wherein B is COOH or a pharmaceutically acceptable salt thereof, COOR 8 or CONR 9 R 10 .
31 . A compound in accordance with claim 30 where the phenyl group is attached to the 2 position of the tetrahydronaphthalene nucleus.
32 . A compound in accordance with claim 31 where the configuration about the ▴ 4 double bond is trans.
33 . A compound in accordance with claim 32 where the B group represents COOH, COOCH 3 or COOC 2 H 5 , R 3 is attached to the 3 position of the tetrahydronaphthalene nucleus and configuration about the ▴ 2 double bond is trans.
34 . A compound in accordance with claim 33 where B is COOH.
35 . A compound in accordance with claim 33 where B is COOC 2 H 5 .
36 . A compound in accordance with claim 32 where the B group represents COOH, COOCH 3 or COOC 2 H 5 , R 3 is attached to the 3 position of the tetrahydronaphthalene nucleus and configuration about the ▴ 2 double bond is cis.
37 . A compound in accordance with claim 36 where B is COOH.
38 . A compound in accordance with claim 36 where B is COOC 2 H 5 .
39 . A compound of the formula
wherein x is S or O;
R 2 is hydrogen or lower alkyl;
R 3 is hydrogen or lower alkyl, 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.
40 . A compound in accordance with claim 39 where X is S.
41 . A compound in accordance with claim 40 wherein R 2 is methyl.
42 . A compound in accordance with claim 41 wherein B is COOH or a pharmaceutically acceptable salt thereof, COOR 8 or CONR 9 R 10 .
43 . A compound in accordance with claim 42 where the cyclopropyl group is attached to the 6 position of the thiochroman nucleus.
44 . A compound in accordance with claim 43 where the configuration about the ▴ 4 double bond is trans.
45 . A compound in accordance with claim 44 where the B group represents COOH, COOCH 3 or COOC 2 H 5 , R 3 is attached to the 7 position of the thiochroman nucleus, configuration about the cyclopropane ring is trans and configuration about the ▴ 2 double bond is trans.
46 . A compound in accordance with claim 45 where the B group represents COOH, COOCH 3 or COOC 2 H 5 , R 3 is attached to the 7 position of the thiochroman nucleus, configuration about the cyclopropane ring is cis and configuration about the ▴ 2 double bond is trans.
47 . A compound in accordance with claim 46 where B is COOH.
48 . A compound in accordance with claim 46 where B is COOC 2 H 5 .
49 . A compound in accordance with claim 44 where the B group represents COOH, COOCH 3 or COOC 2 H 5 , R 3 is attached to the 7 position of the thiochroman nucleus, configuration about the cyclopropane ring is cis and configuration about the ▴ 2 double bond is cis.
50 . A compound in accordance with claim 49 where B is COOH.
51 . A compound in accordance with claim 49 where B is COOC 2 H 5 .Join the waitlist — get patent alerts
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