Patent EP0126970A2 successfully refreshed from Google Patents.
EP0126970A2
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Anxiolytic and anti-depressant thienopyridine derivatives
Assignee: Beecham Group PLC
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Filing: 1984-04-24
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Granted: —
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Expires: 2004-04-24
Abstract
Abstract Compounds of formula (I) and pharmaceutically acceptable salts thereof: wherein: G together with the two carbon atoms to which it is bonded is a thieno moiety; R, is phenyl optionally substituted by one or more C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylthio, hydroxy, C 2 - 7 alkanoyl, halo, trifuluoromethyl, nitro, amino optionally substituted by one or two C 1-6 alkyl groups or by C 2 - 7 alkanoyl, cyano, carbamoyl or carboxy groups; or pyridyl optionally substituted by C 1-6 alkyl or halo; R 6 is hydrogen, c 1-6 alkyl or phenyl optionally substituted as defined hereinbefore for R 1 when phenyl; R 8 is hydrogen, one of the optional substituents recited hereinbefore for R, when phenyl or phenyl optionally substituted as defined hereinbefore for R, when phenyl; and either R 2 is hydrogen, or C 1-6 alkyl optionally substituted by hydroxy, amino disubstituted by C 1-6 alkyl, or phenyl optionally substituted as defined hereinbefore for R, when phenyl; R 3 and R 4 together represent a bond; R 5 and R 7 together represent a bond; and R 9 is hydrogen and R 10 is hydroxy, C 1-6 alkoxy or amino optionally substituted by one or two independently selected C 1-6 alkyl groups or by phenyl optionally substituted as defined hereinbefore for R, when phenyl, or Rg and R, o together represent a bond; or R 2 and R 3 together represent a bond; R 4 and R 5 together represent a bond; and R 7 is hydrogen, C 1-6 alkyl optionally substituted by hydroxy, amino disubstituted by c 1-6 alkyl, or phenyl optionally substituted as defined hereinbefore for R, when phenyl; and R 9 and R 10 together represent a bond, having pharmacological activity, a process and intermediates for their preparation, compositions containing them and their use in the treatment of mammals.
Inventors
- 👤 Mervyn Thompson
- 👤 Ian Thomson Forbes
Bibliographic Details
Application Number
—
Jurisdiction
EP
Data Source
google_patents
Last Synchronized
2026-11-01 23:02
CPC Classifications
C; C07; C07D; C07D495/00; C07D495/02; C07D495/04; C07D333/00; C07D333/02; C07D333/04; C07D333/26; C07D333/30; C07D333/36; C07D495/12; C07D495/14
Claims Analysis
Total Claims: 13
Claim 1
Independent Claim
288 words
A compound of formula (I) or a pharmaceutically acceptable salt thereof: wherein: G together with the two carbon atoms to which it is bonded is a thieno moiety; R 1 is phenyl optionally substituted by one or more C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylthio, hydroxy, C 2-7 alkanoyl, halo, trifluoromethyl, nitro, amino optionally substituted by one or two C 1-6 alkyl groups or by C 2 - 7 alkanoyl, cyano, carbamoyl or carboxy groups; or pyridyl optionally substituted by C 1-6 alkyl or halo; R 6 is hydrogen, C 1-6 alkyl or phenyl optionally substituted as defined hereinbefore for R 1 when phenyl; R 8 is hydrogen, one of the optional substituents recited hereinbefore for R 1 when phenyl or phenyl optionally substituted as defined hereinbefore for R 1 when phenyl; and either R2 is hydrogen, or C 1-6 alkyl optionally substituted by hydroxy, amino disubstituted by C 1-6 alkyl, or phenyl optionally substituted as defined hereinbefore for R I when phenyl; R 3 and R 4 together represent a bond; R S and R7 together represent a bond; and Rg is hydrogen and R 10 is hydroxy, C 1-6 alkoxy or amino optionally substituted by one or two independently selected C 1-6 alkyl groups or by phenyl optionally substituted as defined herinbefore for R 1 when phenyl, or Rg and R 10 together represent a bond; or R 2 and R 3 together represent a bond; R 4 and R 5 together represent a bond; and R 7 is hydrogen, C 1-6 alkyl optionally substituted by hydroxy, amino disubstituted by C 1-6 alkyl, or phenyl optionally substituted as defined hereinbefore for R 1 when phenyl; and R9 and R 10 together represent a bond.
Claim 2
Dependent Claim
288 words
A compound of formula (I) or a pharmaceutically acceptable salt thereof: wherein: G together with the two carbon atoms to which it is bonded is a thieno moiety; R 1 is phenyl optionally substituted by one or more C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylthio, hydroxy, C 2-7 alkanoyl, halo, trifluoromethyl, nitro, amino optionally substituted by one or two C 1-6 alkyl groups or by C 2 - 7 alkanoyl, cyano, carbamoyl or carboxy groups; or pyridyl optionally substituted by C 1-6 alkyl or halo; R 6 is hydrogen, C 1-6 alkyl or phenyl optionally substituted as defined hereinbefore for R 1 when phenyl; R 8 is hydrogen, one of the optional substituents recited hereinbefore for R 1 when phenyl or phenyl optionally substituted as defined hereinbefore for R 1 when phenyl; and either R2 is hydrogen, or C 1-6 alkyl optionally substituted by hydroxy, amino disubstituted by C 1-6 alkyl, or phenyl optionally substituted as defined hereinbefore for R I when phenyl; R 3 and R 4 together represent a bond; R S and R7 together represent a bond; and Rg is hydrogen and R 10 is hydroxy, C 1-6 alkoxy or amino optionally substituted by one or two independently selected C 1-6 alkyl groups or by phenyl optionally substituted as defined herinbefore for R 1 when phenyl, or Rg and R 10 together represent a bond; or R 2 and R 3 together represent a bond; R 4 and R 5 together represent a bond; and R 7 is hydrogen, C 1-6 alkyl optionally substituted by hydroxy, amino disubstituted by C 1-6 alkyl, or phenyl optionally substituted as defined hereinbefore for R 1 when phenyl; and R9 and R 10 together represent a bond.
Claim 3
Dependent Claim
48 words
A compound according to claim 1, wherein the thieno moiety formed by G and the two carbon atoms to which it is bonded is fused along its 2,3-face to the pyridine or dihydropyridine ring depicted in formula ,(I) in claim 1, in either the [2,3-b] or [3,2-b] orientation.
Claim 4
Dependent Claim
47 words
A compound according to claim 1 or 2 wherein the thieno moiety formed by G and the two carbon atoms to which it is bonded is fused along its 2,3-face to the pyridine or dihydropropyridine ring depicted in formula (I) in claim 1 in the [3,2-b] orientation.
Claim 5
Dependent Claim
44 words
A compound according to claim 1 wherein the thieno moiety formed by G and the two carbon atoms to which it is bonded is fused along its 3,4-face to the b-face of the pyridine or dihydropyridine ring depicted in formula (I) in claim 1.
Claim 6
Dependent Claim
44 words
A compound according to any preceding claim wherein Rg and R 10 together represent a bond, R 6 is hydrogen or C 1-6 alkyl and R 8 is hydrogen or one of the optional substituents recited in claim 1 for R l when phenyl.
Claim 7
Dependent Claim
39 words
A compound according to any one of claims 1 to 4 wherein Rg is hydrogen and R 10 is hydroxy or Cl- 6 alkoxy, R2 is hydrogen and R 6 and R 8 are as defined in claim 5.
Claim 8
Dependent Claim
60 words
A compound according to any one of claims 1 to 4 and 6 which is 7-(2-phenylhydrazino)-thieno[3,2-b]pyridine-6-carboxylic acid, ethyl ester, 7-(4-chlorophenylhydrazino)-thieno[3,2-blpyridine-6-carboxylic acid, ethyl ester, 7-(2-(4-nitrophenyl)hydrazino)-thieno[3,2-b]pyridine-6-carboxylic acid, ethyl ester, 7-(2-(4-isopropylphenyl)hydrazino)-thieno[3,2-b]-pyridine-6-carboxylic acid, ethyl ester, 7-(2-(4-methylphenyl)hydrazino)-thieno[3,2-b]pyridine -6-carboxylic acid, ethyl ester, 7-(2-(2-pyridyl)hydrazino)-thieno[3,2-b]pyridine-6-carboxylic acid, ethyl ester, 7-(2-(4-methoxyphenyl)hydrazino)-thieno[3,2-b]pyridine-6-carboxylic acid, ethyl ester, 5-methyl-7-(2-phenylhydrazino)-thieno[3,2-b]pyridine-6-carboxylic acid, ethyl ester, or 7-(2-(4-chlorophenyl)hydrazino)-5-methyl-thieno[3,2-b]- pyridine-6-carboxylic acid, ethyl ester, or a pharmaceutically acceptable salt thereof.
Claim 9
Dependent Claim
35 words
A compound according to any one of claims 1 to 5 which is 2-(4-chlorophenyl)-2,5-dihydro-4-methyl-3H-pyrazolo-[3,4-d]thieno[3,2-b]pyridin-3-one, 2-(4-chlorophenyl)-2,5-dihydro-3H-pyrazoloI3,4-d] -thieno[3,2-b]pyridin-3-one, 2-(3,5-dichlorophenyl)-2,5-dihydro-3H-pyrazolo[3,4-d]-thieno[3,2-b]pyridin-3-one, 2,5-dihydro-2-(4-methylphenyl)-3H-pyrazolo[3,4-d] -thieno-[3,2-b]pyridin-3-one, 2,5-dihydro-2-(4-methoxyphenyl)-3H-pyrazolo[3,4-d]-thieno[3,2-b]pyridin-3-one, 2,5-dihydro-4-methyl-2-phenyl-3H-pyrazolo[3,4-d]thieno-[3,2-b]pyridin-3-one, 2-(4-chlorophenyl)-2,5-dihydro-4,8-dimethyl-3H-pyrazolo -[3,4-d]thieno[2,3-b]pyridin-3-one, 2-(4-chlorophenyl)-2,5-dihydro-7-ethyl-3H-pyrazolo-[3,4-d]thieno[2,3-b]pyridin-3-one, 2-(4-chlorophenyl)-2,5-dihydro-7-ethyl-4-methyl-3H-pyrazolo[3,4-d]thieno[2,3-b]pyridin-3-one, 2,5-dihydro-2-(2-pyridyl)-3H-pyrazolo[3,4-d]thieno-[3,2-b]pyridin-3-one, or 2-(4-chlorophenyl)-2,5-dihydro-3H-pyrazolo[3,4-d] -thieno-[3,4-b]pyridin-3-one, or a pharmaceutically acceptable salt thereof.
Claim 10
Dependent Claim
31 words
9 A pharmaceutical composition, which comprises a compound according to any one of claims 1 to 8 of formula (I) or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
Claim 11
Dependent Claim
375 words
10 A process for the preparation of a compound according to any one of claims 1 to 8 of formula (I) or a pharmaceutically acceptable salt thereof which process comprises the reaction of a compound of formula (XVI): or a salt thereof, wherein i) when Rg and R 10 in the desired compound of formula (I) are hydrogen, and R 10 1 respectively, where R 10 1 is hydroxy, C 1-6 alkoxy or amino optionally substituted by one or two independently selected C I - 6 alkyl groups or by phenyl optionally substituted as defined in claim 1 for R 1 when phenyl; X is halo; Y is COR 10 1 as hereinbefore defined or nitrile; and the remaining variables are as defined in claim 1; with a compound of formula R 2 HN-NH-R 1 where R 1 and R 2 are as defined in claim 1; and thereafter, in the resultant compound, when Y is nitrile, converting Y to COR 10 1 as hereinbefore defined; and optionally converting R 10 1 to other R 10 1 ; when R 9 and R 10 in the desired compound of ii) formula (I) together represent a bond; a) X is NR 2 -NH-R 1 where R l and R 2 are as hereinbefore defined and Y is COR 11 where R 11 is halo or Y is COR 10 2 where R 10 2 is hydroxy or C 1-6 alkoxy and the compound of formula (XVI) or the salt thereof is optionally prepared by process variant i) hereinbefore optionally followed by salification; b) X is halo, and Y is CON(NR 2 R 15 )R 1 where R 1 and R 2 are as hereinbefore defined; and Rl 5 is hydrogen or a labile deactivating N-protecting group; c) X is C 1-6 alkoxyamino or azido and Y is CONHR 1 where R 1 is as hereinbefore defined; to cyclise; and thereafter, in the resultant compound of formula (I) wherein R 9 and R 10 together represent a bond; optionally converting R 2 or R7 hydrogen to other R 2 or R 7 ; and, in the resultant compound of formula (I), optionally converting R 8 to other R 8 ; and optionally forming a pharmaceutically acceptable salt.
Claim 12
Dependent Claim
19 words
11 A compound of formula (XVI) as in claim 10, wherein the variables are as defined in claim 10.
Claim 13
Dependent Claim
34 words
12 A compound according to any one of claims 1 to 8 of formula (I) or a pharmaceutically acceptable salt thereof, for use in the treatment of CNS disorders, in particular anxiety or depression.
References Cited (Backward Citations)
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