C.sub.4 -amide substituted compounds and their use as therapeutic agents
AssigneeSmithKline Beecham Corporation
InventorsAntonio Kuok Keong Vong, Mervyn Thompson, John Morris Evans, Helen Kate Ann Morgan
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Abstract
The invention provides certain 5 and/or 8 substituted benzopyran, pyranopyridine or tetrahydroquinaline compounds having C.sub.4 -amide substituent and processes for making them. The compounds described are useful in treating and/or preventing certain disorders.
Claims16
A compound which is trans-6-Acetyl-4-(3-azidobenzoylamino)-3,4-dihydro-8-iodo-2,2-dimethyl-2H- 1-benzopyran-3-ol.
A compound which is trans-8-Bromo-4-(3-bromo4-fluorobenzoylamino)-6-ethyl-3,4-dihydro-2,2-dime thyl-2H-1-benzopyran-3-ol.
A compound which is trans-6-Acetyl4S-(3-azidobenzoylamino)-3,4-dihydro-8-iodo-2,2-dimethyl-2H- 1-benzopyran-3R-ol.
A compound which is trans 6-Acetyl4-(4-fluorophenylbenzoylamino)-3,4-dihydro-2,2-dimethyl-8-(2-pheny lethyl)-2H-1-benzopyran-3-ol.
A compound which is trans 6-Acetyl-4-(4-fluorophenylbenzoylamino)-3,4-dihydro-2,2-dimethyl-8-(2-phen ylethenyl-)-2H-1-pyran-3-ol.
A compound which is (.+-.)-10-bromo-2,2-dimethyl-trans4-(4-fluorobenzoylamino)-3,4,6,7,8,9-hex ahydro-6-oxo-naphthaleno3,2-b!pyran-3-ol.
A compound which is trans-3R,4S-6-Acetyl-4-(3-ethoxymethylbenzoylamino)-3-4-dihydro-8-iodo-2,2 -dimethylben.degree.b!pyran-3-ol.
A compound which is trans-3R,4S-6-Acetyl-4-(3-Acetyloxymethylbenzoylamino)-3,4-dihydro-8-iodo- 2,2dimethylbenzolb!pyran-3-ol.
A compound which is trans-3R,4S-6-Acetyl-3,4-dihydro-4-(3-hydroxymethylbenzoylamino)-8-iodo-2, 2-dimethylbenzob!pyran-3-ol.
A compound which is (.+-.)-2,2-dimethyl-trans-4-(3-chloro4-fluorobenzoylamino-3,4,6,7,9,9-hexa hydro-6-oxo-naphthaleno3,2-b!pyran-3-ol.
A compound which is cis 6-Acetyl4S-(3-chlorobenzoylamino)-3,4-Dihydro-2,2-dimethyl-8-hydroxymethyl -2H-benzolb!pyran-3S-ol.
A compound which is cis 8-Acetoxymethyl-6-acetyl4S-(3-chlorobenzoylamino)-3,4dihydro-2,2-dimethyl- 2H-benzob!pyran-3S-ol.
A method of treatment of anxiety, mania, depression, the effects associated with withdrawal from substances of abuse, a disorder treatable and/or preventable with anti-convulsive agents, Parkinson's disease, psychosis, migraine, cerebral ischaemia, schizophrenia, OCD, a panic disorder and/or agression in a sufferer, comprising administering to the sufferer in need thereof an effective amount of a compound selected from the group consisting of:
- trans-6-Acetyl4-(3-azidobenzoylamino)-3,4-dihydro-8-iodo-2,2-dimethyl-2H-1 -benzopyran-3-ol;
- trans-8Bromo-4-3-bromo-4-fluorobenzoylamino-6-ethyl-3,4-dihydro-2.2-dimethy l-2H-1-benzopyran-3-ol;
- trans-6-Acetyl-4S-(3-azidobenzoylamino)-3,4-dihydro-8-iodo-2,2-dimethyl1-2H -1-benzopyran-3R-ol;
- trans 6-Acetyl4-(4-fluorophenylbenzoylamino)-3,4-dihydro-2,2-dimethyl-8-(2-pheny lethyl)-2H-1 -benzopyran-3-ol;
- trans 6-Acetyl-4-(4-fluorophenylbenzoylamino -3,4-dihydro-2,2-dimethyl-8-(2-phenylethenyl)-2H-1-benzopyran-3-ol;
- (.+-.)-10-bromo-2,2-dimethyl-trans-4-(4-fluorobenzoylamino)-3,4,6,7,8,9-hex ahydro-6-oxo-naphthaleno3,2-b!pyran-3-ol;
- trans-3R,4S-6-Acetyl4-(3-ethoxymethylbenzoylamino)-3-4-dihydro-8-iodo-2,2-d imethylbenzob!pyran-3-ol;
- trans-3R,4S-6-Acetyl4-(3-Acetyloxymethylbenzoylamino)-3,4dihydro-8-iodo-2,2 dimethylbenzob!pyran-3-ol;
- trans-3R,4S-6-Acetyl-3,4-dihydro-4-(3-hydroxymethylbenzoylamino)-8-iodo-2,2 -dimethylbenzob!pyran-3-ol;
- (.+-.)-2,2-dimethyl-trans-4-(3-chloro-4-fluorobenzoylamino-3,4,6,7,8,9-hexa hydro-6-oxo-naphthaleno3,2-b!pyran-3-ol;
- cis 6-Acetyl-4S-(3-chlorobenzoylamino)-3,4-Dihydro-2,2-dimethyl-8-hydroxymethy l-2H-benzolb!pyran-3S-ol:
- or
- cis 8-Acetoxymethyl-6-acetyl4S-(3-chlorobenzoylamino)-3,4dihydro-2,2-dimethyl- 2H-benzob!pyran-3S-ol or a pharmaceutically acceptable salt thereof.
A pharmaceutical composition comprising a compound selected from the group consisting of:
- trans-6-Acetyl-4-(3-azidobenzoylamino)-3,4-dihydro-8-iodo-2,2-dimethyl-2H-1 -benzopyran-3-ol;
- trans-8-Bromo-4-(3-bromo-4-fluorobenzoylamino)-6-ethyl-3,4-dihydro-2,2-dime thyl-2H-1-benzopyran-3-ol;
- trans-6-Acetyl-4S-(3-azidobenzoylamino)-3,4-dihydro-8-iodo-2,2-dimethyl-2H- 1-benzopyran-3R-ol;
- trans 6-Acetyl-4-(4-fluorophenylbenzoylamino)-3,4-dihydro-2,2-dimethyl-8-(2-phen ylethyl)-2H-1-benzopyran-3-ol;
- trans 6-Acetyl-4-(4-fluorophenylbenzoylamino)-3,4-dihydro-2,2-dimethyl-8-(2-phen ylethyl)-2H-1-benzopyran-3-ol;
- (.+-.)-10-bromo-2,2-dimethyl-trans-4-(4-fluorobenzoylamino)-3,4,6,7,8,9-hex ahydro-6-oxo-naphthaleno3,2-b!pyran-3-ol;
- trans-3R,4S-6-Acetyl-4-(3-ethoxymethylbenzoylamino)-3-4-dihydro-8-iodo-2,2- dimethylbenzob!pyran-3-ol;
- trans-3R,4S-6-Acetyl-4-(3-Acetyloxymethylbenzoylamino)-3,4-dihydro-8-iodo-2 ,2dimethylbenzob!pyran-3-ol;
- trans-3R,4S-6-Acetyl-3,4dihydro-4-(3-hydroxymethylbenzoylamino)-8-iodo-2,2- dimethylbenzob!pyran-3-ol;
- (.+-.)-2,2-dimethyl-trans4-(3-chloro-4-fluorobenzoylamino-3,4,6,7,8,9-hexah ydro-6-oxo-naphthaleno3,2-b!pyran-3-ol;
- cis 6-Acetyl-4S-(3-chlorobenzoylamino)-3,4-Dihydro-2,2-dimethyl-8-hydroxymethy l-2H-benzob!pyran-3S-ol;
- or
- cis 8-Acetoxymethyl-6-acetyl4S-(3-chlorobenzoylamino)-3,4dihydro-2,2-dimethyl- 2H-benzob!pyran-3S-ol or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.
Dependencies are inferred from the claim text.