US5354752A
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US
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Disubstituted acetylenes bearing a diazinyl group having retinoid like activity
Assignee: Allergan Inc
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Filing: 1993-10-28
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Granted: 1994-10-11
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Expires: 2013-10-28
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 pyridazinyl, pyrimidinyl or pyrazinyl; n is 0-4; 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
2026-10-30 06:07
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: 25
Claim 1
Independent Claim
277 words
A compound of the formula ##STR11## where X is S or O; R is hydrogen or lower alkyl; A is pyridazinyl, pyrimidinyl or pyrazinyl; n is 0-4; 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 2
Dependent Claim
277 words
A compound of the formula ##STR11## where X is S or O; R is hydrogen or lower alkyl; A is pyridazinyl, pyrimidinyl or pyrazinyl; n is 0-4; 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 3
Dependent Claim
9 words
A compound of claim 1 where X is S.
Claim 4
Dependent Claim
9 words
A compound of claim 1 where X is O.
Claim 5
Dependent Claim
9 words
A compound of claim 3 where A is pyridazinyl.
Claim 6
Dependent Claim
9 words
A compound of claim 2 where A is pyrimidinyl.
Claim 7
Dependent Claim
9 words
A compound of claim 2 where A is pyrazinyl.
Claim 8
Dependent Claim
9 words
A compound of claim 3 where A is pyrazinyl.
Claim 9
Dependent Claim
26 words
A compound of claim 2 where A is pyrimidinyl and B is --CH 2 OH or a lower alkyl ether or lower alkyl acid ester thereof.
Claim 10
Dependent Claim
18 words
A compound of claim 2 where A is pyrimidinyl and B is --CHO or an acetal derivative thereof.
Claim 11
Dependent Claim
9 words
A compound of claim 2 where A is pyridazinyl.
Claim 12
Dependent Claim
9 words
A compound of claim 3 where A is pyrimidinyl.
Claim 13
Dependent Claim
22 words
A compound of claim 5 which is ethyl 5-(4,4-dimethylthiochroman-6-yl)ethynyl-pyrimidin-2-yl-acetate, 5-(4,4-dimethylthiochroman-6-yl)ethynyl-pyrimidin-2-yl-acetic acid, ethyl 5-(4,4-dimethylthiochroman-6-yl) ethynyl-pyrimidin-2-yl-pentanoate, 5-(4,4-dimethylthiochroman-6-yl)ethynyl-pyrimidin-2-yl-pentanoic acid, or a pharmaceutically acceptable salt thereof.
Claim 14
Dependent Claim
21 words
A compound of claim 5 which is ethyl 5-(4,4,7-trimethylthiochroman-6-yl)ethynyl-pyrimidin-2-yl-acetate, 5-(4,4,7-trimethylthiochroman-6-yl)ethynyl-pyrimidin-2-yl-acetic acid, ethyl 5-(4,4,7-trimethylthiochroman-6-yl)ethynyl-pyrimidin-2-yl-pentanoate, 5-(4,4,7-trimethylthiochroman-6-yl)ethynyl-pyrimidin-2-yl-pentanoic acid, or a pharmaceutically acceptable salt thereof.
Claim 15
Dependent Claim
29 words
A compound of claim 4 which is ethyl 5-(4,4-dimethylchroman-6-yl)ethynyl-pyridazin-3-yl-acetate, 5-(4,4-dimethylchroman-6-yl)ethynyl-pyridazin-3-yl-acetic acid, ethyl 5-(4,4-dimethylchroman-6-yl)ethynyl-pyridazin-3-yl-pentanoate, 5-(4,4-dimethylchroman-6-yl)ethynyl-pyridazin-3-yl-pentanoic acid, ethyl 5-(4,4,7-trimethylchroman-6-yl)ethynyl-pyridazin-3-yl-acetate, 5-(4,4,7-trimethylchroman-6-yl)ethynyl-pyridazin-3-yl-acetic acid, ethyl 5-(4,4,7-trimethylchroman-6-yl)ethynyl-pyridazin-3-yl-pentanoate, 5-(4,4,7-trimethylchroman-6-yl)ethynyl-pyridazin-3-yl-pentanoic acid or a pharmaceutically acceptable salt thereof.
Claim 16
Dependent Claim
21 words
A compound of claim 6 which is ethyl 5-(4,4-dimethylthiochroman-6-yl)ethynyl-pyrazin-3-yl-acetate, 5-(4,4-dimethylthiochroman-6-yl)ethynyl-pyrazin-3-yl-acetic acid, ethyl 5-(4,4-dimethylthiochroman-6-yl)ethynyl-pyrazin-3-yl-pentanoate, 5-(4,4-dimethylthiochroman-6-yl)ethynyl-pyrazin-3-yl-pentanoic acid, or a pharmaceutically acceptable salt thereof.
Claim 17
Dependent Claim
21 words
A compound of claim 6 which is ethyl 5-(4,4,7-trimethylthiochroman-6-yl)ethynyl-pyrazin-3-yl-acetate, 5-(4,4,7-trimethylthiochroman-6-yl)ethynyl-pyrazin-3-yl-acetic acid, ethyl 5-(4,4,7-trimethylthiochroman-6-yl)ethynyl-pyrazin-3-yl-pentanoate, 5-(4,4,7-trimethylthiochroman-6-yl)ethynyl-pyrazin-3-yl-pentanoic acid, or a pharmaceutically acceptable salt thereof.
Claim 18
Dependent Claim
29 words
A compound of claim 10 which is ethyl 5-(4,4-dimethylthiochroman-6-yl)ethynyl-pyridazin-3-yl-acetate, 5-(4,4-dimethylthiochroman-6-yl)ethynyl-pyridazin-3-yl-acetic acid, ethyl 5-(4,4-dimethylthiochroman-6-yl)ethynyl-pyridazin-3-yl-pentanoate, 5-(4,4-dimethylthiochroman-6-yl)ethynyl-pyridazin-3-yl-pentanoic acid, ethyl 5-(4,4,7-trimethylthiochroman-6-yl)ethynyl-pyridazin-3-yl-acetate, 5-(4,4,7-trimethylthiochroman-6-yl)ethynyl-pyridazin-3-yl-acetic acid, ethyl 5-(4,4,7-trimethylthiochroman-6-yl)ethynyl-pyridazin-3-yl-pentanoate, 5-(4,4,7-trimethylthiochroman-6-yl)ethynyl-pyridazin-3-yl-pentanoic acid or a pharmaceutically acceptable salt thereof.
Claim 19
Dependent Claim
29 words
A compound of claim 11 which is ethyl 5-(4,4-dimethylchroman-6-yl)ethynyl-pyrimidin-2-yl-acetate, 5-(4,4-dimethylchroman-6-yl)ethynyl-pyrimidin-2-yl-acetic acid, ethyl 5-(4,4-dimethylchroman-6-yl)ethynyl-pyrimidin-2-yl-pentanoate, 5-(4,4-dimethylchroman-6-yl)ethynyl-pyrimidin-2-yl-pentanoic acid, ethyl 5-(4,4,7-trimethylchroman-6-yl)ethynyl-pyrimidin-2-yl-acetate, 5-(4,4,7-trimethylchroman-6-yl)ethynyl-pyrimidin-2-yl-acetic acid, ethyl 5-(4,4,7-trimethylchroman-6-yl)ethynyl-pyrimidin-2-yl-pentanoate, 5-(4,4,7-trimethylchroman-6-yl)ethynyl-pyrimidin-2-yl-pentanoic acid, or a pharmaceutically acceptable salt thereof.
Claim 20
Dependent Claim
32 words
A compound of claim 7 which is ethyl 5-(4,4-dimethylchroman-6-yl)ethynyl-pyrazin-3-yl-acetate, 5-(4,4-dimethylchroman-6-yl)ethynyl-pyrazin-3-yl-acetic acid, ethyl 5-(4,4-dimethylchroman-6-yl)ethynyl-pyrazin-3-yl-pentanoate, 5-(4,4-dimethylchroman-6-yl)ethynyl-pyrazin-3-yl-pentanoic acid, ethyl 5-(4,4,7-trimethylchroman-6-yl) ethynyl-pyrazin-3-yl-acetate, 5-(4,4,7-trimethylchroman-6-yl)ethynyl-pyrazin-3-yl-acetic acid, ethyl 5-(4,4,7-trimethylchroman-6-yl)ethynyl-pyrazin-3-yl-pentanoate, 5-(4,4,7 -trimethylchroman-6-yl) ethynyl-pyrazin-3-yl-pentanoic acid, or a pharmaceutically acceptable salt thereof.
Claim 21
Dependent Claim
286 words
A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of the formula ##STR12## where X is S or O; R is hydrogen or lower alkyl; A is pyridazinyl, pyrimidinyl or pyrazinyl; n is 0-4; 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 22
Dependent Claim
286 words
A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of the formula ##STR12## where X is S or O; R is hydrogen or lower alkyl; A is pyridazinyl, pyrimidinyl or pyrazinyl; n is 0-4; 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 23
Dependent Claim
13 words
A composition according to claim 20 useful for treating psoriasis in a mammal.
Claim 24
Independent Claim
303 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 ##STR13## where X is S or O; R is hydrogen or lower alkyl; A is pyridazinyl, pyrimidinyl or pyrazinyl; n is 0-5; 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 4 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 25
Independent Claim
303 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 ##STR13## where X is S or O; R is hydrogen or lower alkyl; A is pyridazinyl, pyrimidinyl or pyrazinyl; n is 0-5; 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 4 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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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1997-10-10 | 1998-04-11 | 1998-10-11 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2001-10-10 | 2002-04-11 | 2002-10-11 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2005-10-10 | 2006-04-11 | 2006-10-11 | $7700.00 | Window Closed / Lapsed |