Patent US5089509A successfully refreshed from Google Patents.
US5089509A
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Disubstituted acetylenes bearing heteroaromatic and heterobicyclic groups having retinoid like activity
Assignee: Allergan Inc
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Filing: 1989-03-20
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Granted: 1992-02-18
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Expires: 2009-03-20
Abstract
Abstract Retinoid-like activity is exhibited by compounds of the formula ##STR1## where X is S, O, or NR' where R' is hydrogen or lower alkyl; R is hydrogen or lower alkyl; A is pyridyl, thienyl, furyl, pyridazinyl, pyrimidinyl or pyrazinyl; n is 0-2; and B is H, --COOH or a pharmaceutically acceptable salt, ester or amide thereof, --CH 2 OH or an ether or ester derivative, or --CHO or an acetal derivative, or --COR 1 or a ketal derivative where R 1 is --(CH 2 ) m CH 3 where m is 0-4, or a pharmaceutically acceptable salt thereof.
Inventors
- 👤 Roshantha A. S. Chandraratna
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-31 18:50
CPC Classifications
C; C07; C07D; C07D335/00; C07D335/04; C07D335/06; C07D215/00; C07D215/02; C07D215/12; C07D311/00; C07D311/02; C07D311/04; C07D311/58; C07D401/00; C07D401/02; C07D401/06; C07D405/00; C07D405/02; C07D405/06; C07D407/00; C07D407/02; C07D407/06; C07D409/00; C07D409/02; C07D409/06
Claims Analysis
Total Claims: 29
Claim 1
Independent Claim
278 words
A compound of the formula ##STR11## where X is S or O; R is hydrogen or lower alkyl; R 2 is methyl; A is pyridyl; n is 0-2; and B is H, --COOH or a pharmaceutically acceptable salt thereof, or an ester thereof with a saturated aliphatic alcohol of ten or fewer carbon atoms, or with a cyclic or saturated aliphatic cyclic alcohol of 5 to 10 carbon atoms, or with phenol or with a lower alkylphenol, or an amide or a mono or disubstituted amide thereof, the substituents on the amide being selected from a group consisting of saturated aliphatic radicals of ten or fewer carbon atoms, cyclic or saturated aliphatic cyclic radicals of 5 to 10 carbon atoms, and phenyl or lower alkylphenyl radicals, or B is CH 2 OH or an ester derivative thereof derived from a saturated aliphatic acid of ten or fewer carbon atoms, or from a cyclic or saturated aliphatic cyclic acid of 5 to 10 carbon atoms, or from benzoic acid, or an ether derivative thereof derived from a saturated aliphatic radical of ten or fewer carbon atoms, or from a cyclic or saturated aliphatic cyclic radical of 5 to 10 carbon atoms, or from phenyl or lower alkylphenyl radical, or B is --CHO or a lower alkyl acetal derivative thereof, or an acetal derivative thereof formed with a lower alkyl diol, or B is --COR 1 or a lower alkyl ketal derivative thereof, or a ketal derivative thereof formed with a lower alkyl diol, where R 1 is --(CH 2 ) m CH 3 where m is 0-4, or a pharmaceutically acceptable salt of the compound defined in said formula.
Claim 2
Dependent Claim
278 words
A compound of the formula ##STR11## where X is S or O; R is hydrogen or lower alkyl; R 2 is methyl; A is pyridyl; n is 0-2; and B is H, --COOH or a pharmaceutically acceptable salt thereof, or an ester thereof with a saturated aliphatic alcohol of ten or fewer carbon atoms, or with a cyclic or saturated aliphatic cyclic alcohol of 5 to 10 carbon atoms, or with phenol or with a lower alkylphenol, or an amide or a mono or disubstituted amide thereof, the substituents on the amide being selected from a group consisting of saturated aliphatic radicals of ten or fewer carbon atoms, cyclic or saturated aliphatic cyclic radicals of 5 to 10 carbon atoms, and phenyl or lower alkylphenyl radicals, or B is CH 2 OH or an ester derivative thereof derived from a saturated aliphatic acid of ten or fewer carbon atoms, or from a cyclic or saturated aliphatic cyclic acid of 5 to 10 carbon atoms, or from benzoic acid, or an ether derivative thereof derived from a saturated aliphatic radical of ten or fewer carbon atoms, or from a cyclic or saturated aliphatic cyclic radical of 5 to 10 carbon atoms, or from phenyl or lower alkylphenyl radical, or B is --CHO or a lower alkyl acetal derivative thereof, or an acetal derivative thereof formed with a lower alkyl diol, or B is --COR 1 or a lower alkyl ketal derivative thereof, or a ketal derivative thereof formed with a lower alkyl diol, where R 1 is --(CH 2 ) m CH 3 where m is 0-4, or a pharmaceutically acceptable salt of the compound defined in said formula.
Claim 3
Dependent Claim
18 words
A compound of claim 1 where X is S, R is hydrogen, and n is 0 or 1.
Claim 4
Dependent Claim
24 words
A compound of claim 2 where B is --COOH or a pharmaceutically acceptable salt, lower alkyl ester or mono- or di-lower alkyl amide thereof.
Claim 5
Dependent Claim
2 words
Ethyl 6-(2-(4,4-dimethylthiochroman-6-yl)ethynyl)nicotinate.
Claim 6
Dependent Claim
2 words
Ethyl 6-(2-(4,4-dimethylthiochroman-6-yl)ethynyl)nicotinate.
Claim 7
Dependent Claim
8 words
6-(2-(4,4-dimethylthiochroman-6-yl)ethynyl)nicotinic acid or a pharmaceutically acceptable salt thereof.
Claim 8
Dependent Claim
8 words
6-(2-(4,4-dimethylthiochroman-6-yl)ethynyl)nicotinic acid or a pharmaceutically acceptable salt thereof.
Claim 9
Dependent Claim
30 words
A compound of the formula ##STR12## where n is 0 or 1 and where B is --CH 2 OH or a lower alkyl ether or lower alkyl acid ester thereof.
Claim 10
Dependent Claim
30 words
A compound of the formula ##STR12## where n is 0 or 1 and where B is --CH 2 OH or a lower alkyl ether or lower alkyl acid ester thereof.
Claim 11
Dependent Claim
8 words
A compound of claim 6 which is 6-(2-(4,4-dimethylthiochroman-6-yl)-ethynyl)-3-pyridylmethanol.
Claim 12
Dependent Claim
14 words
A compound of claim 2 where B is --CHO or an acetal derivative thereof.
Claim 13
Dependent Claim
8 words
A compound of claim 8 which is 2-(2-(4,4-dimethylthiochroman-6-yl)-ethynyl)-5-pyridinecarboxaldehyde.
Claim 14
Dependent Claim
266 words
A compound of the formula ##STR13## where R is lower alkyl, n is 0 or 1, and B is H, --COOH or a pharmaceutically acceptable salt thereof, or an ester thereof with a saturated aliphatic alcohol of ten or fewer carbon atoms, or with a cyclic or saturated aliphatic cyclic alcohol of 5 to 10 carbon atoms, or with phenol or with a lower alkylphenol, or an amide or a mono or di-substituted amide thereof, the substituents on the amide being selected from a group consisting of saturated aliphatic radicals of ten or fewer carbon atoms, cyclic or saturated aliphatic cyclic radicals of 5 to 10 carbon atoms, and phenyl or lower alkylphenyl radicals, or B is CH 2 OH or an ester derivative thereof derived from a saturated aliphatic acid of ten or fewer carbon atoms, or from a cyclic or saturated aliphatic cyclic acid of 5 to 10 carbon atoms, or from benzoic acid, or an ether derivative thereof derived from a saturated aliphatic radical of ten or fewer carbon atoms, or from a cyclic or saturated aliphatic cyclic radical of 5 to 10 carbon atoms, or from phenyl or lower alkylphenyl radical, or B is --CHO or a lower alkyl acetal derivative thereof, or an acetal derivative thereof formed with a lower alkyl diol, or B is --COR 1 or a lower alkyl ketal derivative thereof, or a ketal derivative thereof formed with a lower alkyl diol, where R 1 is --(CH 2 ) m CH 3 where m is 0-4, or a pharmaceutically acceptable salt of the compound defined in said formula.
Claim 15
Dependent Claim
266 words
A compound of the formula ##STR13## where R is lower alkyl, n is 0 or 1, and B is H, --COOH or a pharmaceutically acceptable salt thereof, or an ester thereof with a saturated aliphatic alcohol of ten or fewer carbon atoms, or with a cyclic or saturated aliphatic cyclic alcohol of 5 to 10 carbon atoms, or with phenol or with a lower alkylphenol, or an amide or a mono or di-substituted amide thereof, the substituents on the amide being selected from a group consisting of saturated aliphatic radicals of ten or fewer carbon atoms, cyclic or saturated aliphatic cyclic radicals of 5 to 10 carbon atoms, and phenyl or lower alkylphenyl radicals, or B is CH 2 OH or an ester derivative thereof derived from a saturated aliphatic acid of ten or fewer carbon atoms, or from a cyclic or saturated aliphatic cyclic acid of 5 to 10 carbon atoms, or from benzoic acid, or an ether derivative thereof derived from a saturated aliphatic radical of ten or fewer carbon atoms, or from a cyclic or saturated aliphatic cyclic radical of 5 to 10 carbon atoms, or from phenyl or lower alkylphenyl radical, or B is --CHO or a lower alkyl acetal derivative thereof, or an acetal derivative thereof formed with a lower alkyl diol, or B is --COR 1 or a lower alkyl ketal derivative thereof, or a ketal derivative thereof formed with a lower alkyl diol, where R 1 is --(CH 2 ) m CH 3 where m is 0-4, or a pharmaceutically acceptable salt of the compound defined in said formula.
Claim 16
Dependent Claim
15 words
A compound of claim 10 which is 6-(2-(4,4,7-trimethylthiochroman-6-yl)ethynyl)nicotinic acid or a pharmaceutically acceptable salt thereof.
Claim 17
Dependent Claim
262 words
A compound of the formula ##STR14## where n is 0 or 1, and B is H, --COOH or a pharmaceutically acceptable salt thereof, or an ester thereof with a saturated aliphatic alcohol of ten or fewer carbon atoms, or with a cyclic or saturated aliphatic cyclic alcohol of 5 to 10 carbon atoms, or with phenol or with a lower alkylphenol, or an amide or a mono or di-substituted amide thereof, the subtituents on the amide being selected from a group consisting of saturated aliphatic radicals of ten or fewer carbon atoms, cyclic or saturated aliphatic cyclic radicals of 5 to 10 carbon atoms, and phenyl or lower alkylphenyl radicals, or B is CH 2 OH or an ester derivative thereof derived from a saturated aliphatic acid of ten or fewer carbon atoms, or from a cyclic or saturated aliphatic cyclic acid of 5 to 10 carbon atoms, or from benzoic acid, or an ether derivative thereof derived from a saturated aliphatic radical of ten or fewer carbon atoms, or from a cyclic or saturated aliphatic cyclic radical of 5 to 10 carbon atoms, or from phenyl or lower alkylphenyl radical, or B is --CHO or a lower alkyl acetal derivative thereof, or an acetal derivative thereof formed with a lower alkyl diol, or B is --COR 1 or a lower alkyl ketal derivative thereof, or a ketal derivative thereof formed with a lower alkyl diol, where R 1 is --(CH 2 ) m CH 3 where m is 0-4, or a pharmaceutically acceptable salt of the compound defined in said formula.
Claim 18
Dependent Claim
262 words
A compound of the formula ##STR14## where n is 0 or 1, and B is H, --COOH or a pharmaceutically acceptable salt thereof, or an ester thereof with a saturated aliphatic alcohol of ten or fewer carbon atoms, or with a cyclic or saturated aliphatic cyclic alcohol of 5 to 10 carbon atoms, or with phenol or with a lower alkylphenol, or an amide or a mono or di-substituted amide thereof, the subtituents on the amide being selected from a group consisting of saturated aliphatic radicals of ten or fewer carbon atoms, cyclic or saturated aliphatic cyclic radicals of 5 to 10 carbon atoms, and phenyl or lower alkylphenyl radicals, or B is CH 2 OH or an ester derivative thereof derived from a saturated aliphatic acid of ten or fewer carbon atoms, or from a cyclic or saturated aliphatic cyclic acid of 5 to 10 carbon atoms, or from benzoic acid, or an ether derivative thereof derived from a saturated aliphatic radical of ten or fewer carbon atoms, or from a cyclic or saturated aliphatic cyclic radical of 5 to 10 carbon atoms, or from phenyl or lower alkylphenyl radical, or B is --CHO or a lower alkyl acetal derivative thereof, or an acetal derivative thereof formed with a lower alkyl diol, or B is --COR 1 or a lower alkyl ketal derivative thereof, or a ketal derivative thereof formed with a lower alkyl diol, where R 1 is --(CH 2 ) m CH 3 where m is 0-4, or a pharmaceutically acceptable salt of the compound defined in said formula.
Claim 19
Dependent Claim
24 words
A compound of claim 12 where B is --COOH or a pharmaceutically acceptable salt, lower alkyl ester or mono- or di-lower alkyl amide thereof.
Claim 20
Dependent Claim
8 words
6-(2-(4,4-dimethylchroman-6-yl)ethynyl)nicotinic acid or a pharmaceutically acceptable salt thereof.
Claim 21
Dependent Claim
8 words
6-(2-(4,4-dimethylchroman-6-yl)ethynyl)nicotinic acid or a pharmaceutically acceptable salt thereof.
Claim 22
Dependent Claim
2 words
Ethyl 6-(2-(4,4-dimethylchroman-6-yl)ethynyl)nicotinate.
Claim 23
Dependent Claim
2 words
Ethyl 6-(2-(4,4-dimethylchroman-6-yl)ethynyl)nicotinate.
Claim 24
Dependent Claim
22 words
A compound of claim 12 where B is --CH 2 OH or a lower alkyl ether or lower alkyl acid ester thereof.
Claim 25
Dependent Claim
14 words
A compound of claim 12 where B is --CHO or an acetal derivative thereof.
Claim 26
Dependent Claim
287 words
A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of the formula ##STR15## where X is S or O; R is hydrogen or lower alkyl; R 2 is methyl; A is pyridyl; n is 0-2; and B is H, --COOH or a pharmaceutically acceptable salt thereof, or an ester thereof with a saturated aliphatic alcohol of ten or fewer carbon atoms, or with a cyclic or saturated aliphatic cyclic alcohol of 5 to 10 carbon atoms, or with phenol or with a lower alkylphenol, or an amide or a mono or di-substituted amide thereof, the subtituents on the amide being selected from a group consisting of saturated aliphatic radicals of ten or fewer carbon atoms, cyclic or saturated aliphatic cyclic radicals of 5 to 10 carbon atoms, and phenyl or lower alkylphenyl radicals, or B is CH 2 OH or an ester derivative thereof derived from a saturated aliphatic acid of ten or fewer carbon atoms, or from a cyclic or saturated aliphatic cyclic acid of 5 to 10 carbon atoms, or from benzoic acid, or an ether derivative thereof derived from a saturated aliphatic radical of ten or fewer carbon atoms, or from a cyclic or saturated aliphatic cyclic radical of 5 to 10 carbon atoms, or from phenyl or lower alkylphenyl radical, or B is --CHO or a lower alkyl acetal derivative thereof, or an acetal derivative thereof formed with a lower alkyl diol, or B is --COR 1 or a lower alkyl ketal derivative thereof, or a ketal derivative thereof formed with a lower alkyl diol, where R 1 is --(CH 2 ) m CH 3 where m is 0-4, or a pharmaceutically acceptable salt of the compound defined in said formula.
Claim 27
Dependent Claim
287 words
A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of the formula ##STR15## where X is S or O; R is hydrogen or lower alkyl; R 2 is methyl; A is pyridyl; n is 0-2; and B is H, --COOH or a pharmaceutically acceptable salt thereof, or an ester thereof with a saturated aliphatic alcohol of ten or fewer carbon atoms, or with a cyclic or saturated aliphatic cyclic alcohol of 5 to 10 carbon atoms, or with phenol or with a lower alkylphenol, or an amide or a mono or di-substituted amide thereof, the subtituents on the amide being selected from a group consisting of saturated aliphatic radicals of ten or fewer carbon atoms, cyclic or saturated aliphatic cyclic radicals of 5 to 10 carbon atoms, and phenyl or lower alkylphenyl radicals, or B is CH 2 OH or an ester derivative thereof derived from a saturated aliphatic acid of ten or fewer carbon atoms, or from a cyclic or saturated aliphatic cyclic acid of 5 to 10 carbon atoms, or from benzoic acid, or an ether derivative thereof derived from a saturated aliphatic radical of ten or fewer carbon atoms, or from a cyclic or saturated aliphatic cyclic radical of 5 to 10 carbon atoms, or from phenyl or lower alkylphenyl radical, or B is --CHO or a lower alkyl acetal derivative thereof, or an acetal derivative thereof formed with a lower alkyl diol, or B is --COR 1 or a lower alkyl ketal derivative thereof, or a ketal derivative thereof formed with a lower alkyl diol, where R 1 is --(CH 2 ) m CH 3 where m is 0-4, or a pharmaceutically acceptable salt of the compound defined in said formula.
Claim 28
Independent Claim
304 words
A method of treating psoriasis in a mammal which method comprises administering alone or in conjunction with a pharmaceutically acceptable excipient, a therapeutically effective amount of a compound of the formula ##STR16## where X is S or O; R is hydrogen or lower alkyl; R 2 is methyl; A is pyridyl; n is 0-2; and B is H, --COOH or a pharmaceutically acceptable salt thereof, or an ester thereof with a saturated aliphatic alcohol of ten or fewer carbon atoms, or with a cyclic or saturated aliphatic cyclic alcohol of 5 to 10 carbon atoms, or with phenol or with a lower alkylphenol, or an amide or a mono or di-substituted amide thereof, the subtituents on the amide being selected from a group consisting of saturated aliphatic radicals of ten or fewer carbon atoms, cyclic or saturated aliphatic cyclic radicals of 5 to 10 carbon atoms, and phenyl or lower alkylphenyl radicals, or B is CH 2 OH or an ester derivative thereof derived from a saturated aliphatic acid of ten or fewer carbon atoms, or from a cyclic or saturated aliphatic cyclic acid of 5 to 10 carbon atoms, or from benzoic acid, or an ether derivative thereof derived from a saturated aliphatic radical of ten or fewer carbon atoms, or from a cyclic or saturated aliphatic cyclic radical of 5 to 10 carbon atoms, or from phenyl or lower alkylphenyl radical, or B is --CHO or a lower alkyl acetal derivative thereof, or an acetal derivative thereof formed with a lower alkyl diol, or B is --COR 1 or a lower alkyl ketal derivative thereof, or a ketal derivative thereof formed with a lower alkyl diol, where R 1 is --(CH 2 ) m CH 3 where m is 0-4, or a pharmaceutically acceptable salt of the compound defined in said formula.
Claim 29
Independent Claim
304 words
A method of treating psoriasis in a mammal which method comprises administering alone or in conjunction with a pharmaceutically acceptable excipient, a therapeutically effective amount of a compound of the formula ##STR16## where X is S or O; R is hydrogen or lower alkyl; R 2 is methyl; A is pyridyl; n is 0-2; and B is H, --COOH or a pharmaceutically acceptable salt thereof, or an ester thereof with a saturated aliphatic alcohol of ten or fewer carbon atoms, or with a cyclic or saturated aliphatic cyclic alcohol of 5 to 10 carbon atoms, or with phenol or with a lower alkylphenol, or an amide or a mono or di-substituted amide thereof, the subtituents on the amide being selected from a group consisting of saturated aliphatic radicals of ten or fewer carbon atoms, cyclic or saturated aliphatic cyclic radicals of 5 to 10 carbon atoms, and phenyl or lower alkylphenyl radicals, or B is CH 2 OH or an ester derivative thereof derived from a saturated aliphatic acid of ten or fewer carbon atoms, or from a cyclic or saturated aliphatic cyclic acid of 5 to 10 carbon atoms, or from benzoic acid, or an ether derivative thereof derived from a saturated aliphatic radical of ten or fewer carbon atoms, or from a cyclic or saturated aliphatic cyclic radical of 5 to 10 carbon atoms, or from phenyl or lower alkylphenyl radical, or B is --CHO or a lower alkyl acetal derivative thereof, or an acetal derivative thereof formed with a lower alkyl diol, or B is --COR 1 or a lower alkyl ketal derivative thereof, or a ketal derivative thereof formed with a lower alkyl diol, where R 1 is --(CH 2 ) m CH 3 where m is 0-4, or a pharmaceutically acceptable salt of the compound defined in said formula.
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