Back to results
US 6,333,336 B1Granted
Pyrazolo-pyridine derivatives as ligands for GABA receptors
AssigneeMerck Sharp & Dohme Corp.
InventorsWesley Peter Blackaby, Jose Luis Castro Pineiro, Richard Thomas Lewis, Michael Geoffrey Neil Russell, Leslie Joseph Street
Life of this patent
Estimating the term…
Abstract
Pyrazolo[4,3-c]pyridin-3-one derivatives substituted at the 2-position by an optionally substituted aryl or heteroaryl moiety, and having pendant substituents at the 7-position and optionally also at the 6-position, are selective ligands for GABAA receptors, particularly having high affinity for the α2 and/or α3 subunit, and are useful in the treatment and/or prevention of disorders of the central nervous system, including anxiety and convulsions.
Claims10
A compound of formula I, or a salt or prodrug thereof:
- wherein
- R1 represents aryl or heteroaryl, either of which groups may be optionally substituted;
- R2 represents halogen;
- or C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, aryl, aryl(C1-6)alkyl, C3-7 heterocycloalkyl, heteroaryl, heteroaryl(C1-6)alkyl, C2-6 alkoxycarbonyl, C1-6 alkylaminocarbonyl or heteroarylaminocarbonyl, any of which groups may be optionally substituted;
- and
- R3 represents hydrogen, C1-6 alkyl or trifluoromethyl.
3 more elements
A compound selected from:
- 2,5-dihydro-2,7-diphenylpyrazolo[4,3-c]pyridin-3-one;
- 2,5-dihydro-2-phenyl-7-propylpyrazolo[4,3-c]pyridin-3-one;
- 2,5-dihydro-2-(4-methoxyphenyl)-7-propylpyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-7-propylpyrazolo[4,3-c]pyridin-3-one;
- 7-benzyl-2-(4-chlorophenyl)-2,5-dihydropyrazolo[4,3-c]pyridin-3-one;
- 7-benzyl-2,5-dihydro-2-(4-methoxyphenyl)pyrazolo[4,3-c]pyridin-3-one;
- 3,5-dihydro-3-oxo-2-phenyl-2H-pyrazolo[4,3-c]pyridine-7-carboxylic acid propylamide;
- 3,5-dihydro-3-oxo-2-phenyl-2H-pyrazolo[4,3-c]pyridine-7-carboxylic acid thiazol-2-ylamide;
- 2-(4-chlorophenyl)-2,5-dihydro-6-methyl-7-phenylpyrazolo[4,3-c]pyridin-3-one;
- 2,5-dihydro-2-(4-methoxyphenyl)-6-methyl-7-phenylpyrazolo[4,3-c]pyridin-3-one;
- 2,5-dihydro-6-methyl-2,7-diphenylpyrazolo[4,3-c]pyridin-3-one;
- 2,5-dihydro-6-methyl-2-(4-methylphenyl)-7-phenylpyrazolo[4,3-c]pyridin-3-one;
- 2-(4-fluorophenyl)-2,5-dihydro-6-methyl-7-phenylpyrazolo[4,3-c]pyridin-3-one;
- 6-ethyl-2,5-dihydro-2-(4-methoxyphenyl)-7-phenylpyrazolo[4,3-c]pyridin-3-one;
- 6-ethyl-2,5-dihydro-2,7-diphenylpyrazolo[4,3-c]pyridin-3-one;
- 2,5-dihydro-2,7-bis(4-methoxyphenyl)-6-methylpyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-7-(4-methoxyphenyl)-6-methyl -pyrazolo[4,3-c]pyridin-3-one;
- 2,7-bis(4-chlorophenyl)-2,5-dihydro-6-methylpyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-7-(3-methoxyphenyl)-6-methyl -pyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-7-(2-methoxyphenyl)-6-methyl -pyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-6-methyl-7-(thiophen-2-yl)pyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-7-(3-iodophenyl)-6-methylpyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-6-methyl-7-[3-(pyridin-3-yl)phenyl]-pyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-6-methyl-7-[3-(thiophen-2-yl)phenyl]-pyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-6-methyl-7-[3-(3-methyl-1,2,4-oxadiazol-5-yl)phenyl]pyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-6-methyl-7-[3-(pyrrolidin-1-ylcarbonyl)phenyl]pyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-6-methyl-7-[3-(4-methylpiperazin-1-ylcarbonyl)phenyl]pyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-6-methyl-7-[3-(imidazol-1-yl)phenyl]-pyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-6-methyl-7-[4-(pyridin-3-yl)phenyl]-pyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-6-methyl-7-[4-(morpholin-4-yl)phenyl]-pyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-6-methyl-7-[3-nitrophenyl]pyrazolo[4,3-c]pyridin-3-one;
- 7-(3-aminophenyl)-2-(4-chlorophenyl)-2,5-dihydro-6-methylpyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-6-methyl-7-[3-(3-pyridylmethylamino)phenyl]pyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-6-methyl-7-[3-(dimethylamino)phenyl]-pyrazolo[4,3-c]pyridin-3-one;
- N-{3-[2-(4-chlorophenyl)-3,5-dihydro-6-methyl-3-oxo-2H-pyrazolo[4,3-c]pyridin-7-yl]phenyl}methanesulphonamide;
- 2-(4-chlorophenyl)-2,5-dihydro-6-methyl-7-[3-(4H-1,2,4-triazol-4-yl)phenyl]pyrazolo[4,3-c]pyridin-3-one;
- N-{3-[2-(4-chlorophenyl)-3,5-dihydro-6-methyl-3-oxo-2H-pyrazolo[4,3-c]pyridin-7-yl]phenyl}-N′-(ethyl)urea;
- 2-(4-chlorophenyl)-2,5-dihydro-6-methyl-7-[3-(4-methylpiperazin-1-yl)phenyl]pyrazolo[4,3-c]pyridin-3-one;
- 2,5-dihydro-2-phenyl-7-(4-pyridyl)pyrazolo[4,3-c]pyridin-3-one;
- 7-(4-aminophenyl)-2-(4-chlorophenyl)-2,5-dihydro-6-methylpyrazolo[4,3-c]pyridin-3-one;
- 7-(4-acetamidophenyl)-2-(4-chlorophenyl)-2,5-dihydro-6-methyl -pyrazolo[4,3-c]pyridin-3-one;
- 7-[4-(4-(tert-butoxycarbonyl)piperazin-1-yl)phenyl]-2-(4-chlorophenyl)-2,5-dihydro-6-methylpyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-6-methyl-7-[4-(piperazin-1-yl)phenyl]-pyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-6-methyl-7-[4-(pyrrolidin-2-on-1-yl)phenyl]pyrazolo[4,3-c]pyridin-3-one;
- 7-[4-(2-amino-2-methylpropionamido)phenyl]-2-(4-chlorophenyl)-2,5-dihydro-6-methylpyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-6-methyl-7-[4-(4-methylpiperazin-1-yl)phenyl]pyrazolo[4,3-c]pyridin-3-one;
- 7-[4-(N′-tert-butoxycarbonylglycinamido)phenyl]-2-(4-chlorophenyl)-2,5-dihydro-6-methylpyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-6-methyl-7-[4-(1,2,4-triazol-4-yl)phenyl]-pyrazolo[4,3-c]pyridin-3-one;
- and salts and prodrugs thereof.
46 more elements
A compound selected from:
- 2-(4-chlorophenyl)-7-(4-cyanophenyl)-2,5-dihydro-6-methylpyrazolo[4,3-c]pyridin-3-one;
- 7-(3-cyanophenyl)-2-(4-chlorophenyl)-2,5-dihydro-6-methylpyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-6-methyl-7-[4-(pyridin-2-ylmethylamino) phenyl]pyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-7-[4-(N,N-di(cyclopropylmethyl)amino)phenyl]-2,5-dihydro-6-methylpyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-7-[4-(N-cyclopropylmethylamino)phenyl]-2,5-dihydro-6-methylpyrazolo[4,3-c]pyridin-3-one;
- 7-(4-carboxamidophenyl)-2-(4-chlorophenyl)-2,5-dihydro-6-methyl -pyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-7-(3-methoxycarbonylphenyl)-6-methyl -pyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-6-methyl-7-[3-(pyridin-2-ylmethylaminomethyl)phenyl]pyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-6-methyl-7-[4-(pyridin-2-ylmethylaminomethyl)phenyl]pyrazolo[4,3-c]pyridin-3-one;
- 7-[4-(1benzylaminomethyl)phenyl]-2-(4-chlorophenyl)-2,5-dihydro-6-methyl -pyrazolo[4,3-c]pyridin-3-one;
- 7-(3-carboxamidophenyl)-2-(4-chlorophenyl)-2,5-dihydro-6-methyl -pyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-6-methyl-7-[4-(pyrrolidin-1-ylmethyl)phenyl]-pyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-7-[4-(hydroxymethyl)phenyl]-6-methyl -pyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-7-(4-iodophenyl)-6-methylpyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-6-methyl-7-[4-(3-dimethylaminoprop-1-yn -1-yl)phenyl]pyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-7-[4-(imidazol-1-yl)phenyl]-6-methyl -pyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-7-[4-(imidazol-2-yl)phenyl]-6-methyl-pyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-6-methyl-7-[4-(1,2,3-triazol-5-yl)phenyl]-pyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-6-methyl-7-[4-(thiazol-2-yl)phenyl]-pyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-7-(4-hydroxyphenyl)-6-methylpyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-7-[4-(3-hydroxyprop -1-yn-1-yl)phenyl]-6-methylpyrazolo[4,3-c]pyridin-3-one;
- 7-[4-(6-azabenzimidazol-2-yl)phenyl]-2-(4-chlorophenyl)-2,5-dihydro-6-methylpyrazolo[4,3-c]pyridin-3-one;
- 7-(2-acetyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-6-yl)-2-(4-chlorophenyl)-2,5-dihydro-6-methylpyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-7-(2-ethyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-6-yl)-2,5-dihydro-6-methylpyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-7-[2-(dimethylaminomethyl)indol-5-yl]-6-methylpyrazolo[4,3-c]pyridin-3-one;
- 7-(benzimidazol-5-yl)-2-(4-chlorophenyl)-2,5-dihydro-6-methylpyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-6-methyl-7-[4-(4-(morpholin-4-ylmethyl) -1,2,3-triazol-5-yl)phenyl]pyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-6-methyl-7-[4-(4-(morpholin-4-methyl) -1,2,3-triazol-5-yl)phenyl]pyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-6-methyl-7-[4-(2-(pyridin-2-yl)ethyl-1-yn-1-yl)phenyl]pyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-6-methyl-7-[4-(2-(pyridin-2-yl)ethyl)phenyl]pyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-6-methyl-7-[4-(1-methylimidazol-2-yl)phenyl]-pyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-6-methyl-7-[4-(1,2,4-triazol-3-yl)phenyl]-pyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-6-methyl-7-[4-(1-oxa-8-azaspiro[4,5]dec-3-en-3-yl)phenyl]pyrazolo[4,3-c]pyridin-3-one;
- 7-bromo-2-(4-chlorophenyl)-2,5-dihydro-6-methylpyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-7-iodo-6-methylpyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-7-(2-ethoxycarbonylethenyl)-6-methyl -pyrazolo[4,3-c]pyridin-3-one;
- 7-(2-carboxamidoethenyl)-2-(4-chlorophenyl)-2,5-dihydro-6-methylpyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-6-methyl-7-[2-(pyridin-4-yl)ethenyl]-pyrazolo[4,3-c]pyridin-3-one;
- 7-benzyl-2-(4-chlorophenyl)-2,5-dihydro-6-methylpyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-6-methyl-7-[2-(pyridin-4-yl)ethyl]pyrazolo[4,3-c]pyridin-3-one;
- 7-(2-carboxamidoethyl)-2-(4-chlorophenyl)-2,5-dihydro-6-methylpyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-6-methyl-7-[2-(pyridin-2-yl)ethenyl]-pyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-7-(3-dimethylaminoprop -1-ynyl)-6-methyl -pyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-6-methyl-7-(thien-3-yl)pyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-3,5-dihydro-6-methyl-3-oxo-2H-pyrazolo[4,3-c]pyridine -7-carboxylic acid ethyl ester;
- 2-(4-chlorophenyl)-2,5-dihydro-7-[2-(imidazol-1-yl)ethenyl]-6-methyl -pyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-7-ethyl-6-methylpyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-7-(2-methylpropyl)-6-methylpyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-6-methyl-7-[2-(pyridin-2-yl)ethyl]pyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-6-methyl-7-[2-(piperidin-2-yl)ethyl]-pyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-6-methyl-7-[3-(morpholin-4-yl)prop-1-ynyl]-pyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-7-hydroxymethyl-6-methylpyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-6-methyl-7-[2-oxo-3-(1,2,4-triazol-1-yl)propyl]-pyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-7-[3-(imidazol-1-yl)-2-oxopropyl]-6-methyl -pyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-6-methyl-7-[N-(2-methyl-2H-1,2,4-triazol-3-ylmethyl)aminomethyl]pyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-7-(3-methoxycarbonylpropyl)-6-methylpyrazolo[4,3-c]pyridin-3-one;
- 7-(3-carboxamidopropyl)-2-(4-chlorophenyl)-2,5-dihydro-6-methyl -pyrazolo[4,3-c]pyridin-3-one;
- 7-(3-benzoyloxypropyl)-2-(4-chlorophenyl)-2,5-dihydro-6-methylpyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-6-methyl-7-[3-(3-methyl-1,2,4-oxadiazol-5-yl)propyl]pyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-7-(3-cyanopropyl)-2,5-dihydro-6-methylpyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-6-methyl-7-(pyridin-3-yl)pyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-7-[3-(1H-imidazol-2-yl)propyl]-6-methyl -pyrazolo[4,3-c]pyridin-3-one;
- 2-(4-chlorophenyl)-2,5-dihydro-7-(3-hydroxypropyl)-6-methylpyrazolo[4,3-c]pyridin-3-one;
- and salts and prodrugs thereof.
61 more elements
Dependencies are inferred from the claim text.