Pyridine derivatives
AssigneesNovartis AG, Sibia Neurosciences, Inc.
InventorsHans Allgeier, Yves Auberson, Michel Biollaz, Nicholas David Cosford, Fabrizio Gasparini, Roland Heckendorn, Edwin Carl Johnson, Rainer Kuhn, Mark Andrew Varney, Gönül Veliçelebi
Life of this patent
Estimating the term…
Abstract
A compound of formula I wherein X represents an optionally halo-substituted (C2-4)alkynylene group bonded via vicinal unsaturated carbon atoms.
Claims8
A compound of formula I
- wherein
- X represents an optionally halo-substituted (C2-4)alkynylene group bonded via vicinal unsaturated carbon atoms,
- R1 is (C1-4) alkyl, (C1-4)alkoxy, hydroxy(C1-4)alkyl, cyano, ethynyl, carboxy, (C1-4)alkoxycarbonyl, di(C1-4)alkylamino, (C1-6)alkylaminocarbonyl, trifluoromethylphenylaminocarbonyl,
- R2 is hydrogen, hydroxy, (C1-4) alkyl, hydroxy (C1-4) alkyl, (C1-4) alkoxy, carboxy, (C2-5)alkanoyloxy, (C1-4) alkoxycarbonyl, di(C1-4)alkylamino(C1-4)alkanoyl, di(C1-4)alkylaminomethyl, 4-(4-fluoro-benzoyl)-piperidin-1-yl-carboxy, 4-t.-butyloxycarbonyl-piperazin-1-yl-carboxy, 4-(4-azido-2-hydroxybenzoyl)-piperazin-1-yl-carboxy or 4-(4-azido-2-hydroxy-3-iodo-benzoyl)-piperazin-1-yl-carboxy,
- R3 is hydrogen, (C2-4) alkyl, carboxy, (C1-4)alkoxycarbonyl, (C1-4)alkylcarbamoyl, hydroxy(C1-4)alkyl, di(C1-4)alkylaminomethyl, morpholinocarbonyl or 4-(4-fluoro-benzoyl)-piperidin-1-yl-carboxy,
- R4 is hydrogen, hydroxy, (C1-4)alkoxy, carboxy, (C2-5)alkanoyloxy, (C1-4)alkoxycarbonyl, amino(C1-4)alkoxy, di(C1-4)alkylamino(C1-4)alkoxy, di(C1-4)alkylamino(C1-4)alkyl, carboxy (C1-4)alkylcarbonyl, (C1-4)alkoxycarbonyl(C1-4)alkoxy, hydroxy(C1-4)alkyl, di(C1-4)alkylamino(C1-4)alkoxy, m-hydroxy-p-azidophenylcarbonylamino(C1-4)alkoxy, and
- R5 is a group of formula
- wherein
- Ra and Rb independently are hydrogen, hydroxy, halogen, nitro, cyano, carboxy, (C1-4)alkyl, (C1-4)alkoxy, hydroxy(C1-4)alkyl, (C1-4)alkoxycarbonyl, (C2-7)alkanoyl, (C2-5)alkanoyloxy, (C2-5)alkanoyloxy(C1-4)alkyl, trifluoromethyl, trifluoromethoxy, trimethylsilylethynyl, (C2-5)alkynyl, amino, azido, amino (C1-4)alkoxy, (C2-5)alkanoylamino(C1-4)alkoxy, (C1-4)alkylamino(C1-4)alkoxy, di(C1-4)alkylamino(C1-4)alkoxy, (C1-4)alkylamino, di(C1-4)alkylamino, monohalobenzylamino, thienylmethylamino, thienylcarbonylamino, trifluoromethylphenylaminocarbonyl, tetrazolyl, (C2-5)alkanoylamino, benzylcarbonylamino, (C1-4)alkylamino carbonylamino, (C1-4)alkoxycarbonyl-aminocarbonylamino or (C1-4)alkylsulfonyl, Rc is hydrogen, fluorine, chlorine, bromine, hydroxy, (C1-4)alkyl, (C2-5)alkanoyloxy, (C1-4)alkoxy or cyano, and
- Rd is hydrogen, halogen or (C1-4)alkyl, provided that in compounds wherein R2, R3 and R4 are hydrogen, when R1 is methyl, R5 is different from phenyl, 3-methylphenyl, 6-methylpyridin-2-yl and 3-methoxyphenyl, in free form or in form of a pharmaceutically acceptable salt.
A compound which is 2-[2-(Pyridin-3-yl)ethynyl]-6-methyl-pyridine in free form or in form of a pharmaceutically acceptable form.
A method of treating disorders which are mediated fully or in part by mGluR1 or mGluR5, comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound of formula I
- wherein
- X represents an optionally halo-substituted lower alkenylene or alkynylene group bonded via vicinal unsaturated carbon atoms or an azo (—N═N—) group,
- R1 denotes hydrogen, lower alkyl, hydroxy-lower alkyl, lower alkyl-amino, piperidino, carboxy, esterified carboxy, amidated carboxy, unsubstituted or lower alkyl-, lower alkoxy-, halo- and/or trifluoromethyl-substituted N-lower-alkyl-N-phenylcarbamoyl, lower alkoxy, halo-lower alkyl or halo-lower alkoxy,
- R2 denotes hydrogen, lower alkyl, carboxy, esterified carboxy, amidated carboxy, hydroxy-lower alkyl, hydroxy, lower alkoxy or lower alkanoyloxy, 4-(4-fluoro-benzoyl)-piperidin-1-yl-carboxy, 4-t.-butyloxycarbonyl-piperazin-1-yl-carboxy, 4-(4-azido-2-hydroxybenzoyl)-piperazin-1-yl-carboxy or 4-(4-azido-2-hydroxy-3-iodo-benzoyl)-piperazin-1-yl-carboxy,
- R3 represents hydrogen, lower alkyl, carboxy, lower alkoxy-carbonyl, lower alkyl-carbamoyl, hydroxy-lower alkyl, di-lower alkyl-aminomethyl, morpholinocarbonyl or 4-(4-fluoro-benzoyl)-piperidin-1-yl-carboxy,
- R4 represents hydrogen, lower alkyl, hydroxy, hydroxy-lower alkyl, amino-lower alkyl, lower alkylamino-lower alkyl, di-lower alkylamino-lower alkyl, unsubstituted or hydroxy-substituted lower alkyleneamino-lower alkyl, lower alkoxy, lower alkanoyloxy, amino-lower alkoxy, lower alkylamino-lower alkoxy, di-lower alkylamino-lower alkoxy, phthalimido-lower alkoxy, unsubstituted or hydroxy- or 2-oxo-imidazolidin-1-yl-substituted lower alkyleneamino-lower alkoxy, carboxy, esterified or amidated carboxy, carboxy-lower-alkoxy or esterified carboxy-lower-alkoxy, and
- R5 denotes an aromatic or heteroaromatic group which is unsubstituted or substituted by one or more substituents selected from lower alkyl, halo, halo-lower alkyl, halo-lower alkoxy, lower alkenyl, lower alkynyl, unsubstituted or lower alkyl-, lower alkoxy-, halo- and/or trifluoromethyl-substituted phenyl, unsubstituted or lower alkyl-, lower alkoxy-, halo- and/or trifluoromethyl-substituted phenyl-lower alkynyl, hydroxy, hydroxy-lower alkyl, lower alkanoyloxy-lower alkyl, lower alkoxy, lower alkenyloxy, lower alkylenedioxy, lower alkanoyloxy, amino-, lower alkylamino-, lower alkanoylamino- or N-lower alkyl-N-lower alkanoylamino-lower alkoxy, unsubstituted or lower alkyl-lower alkoxy-, halo- and/or trifluoromethyl-substituted phenoxy, unsubstituted or lower alkyl-lower alkoxy-, halo- and/or trifluoromethyl-substituted phenyl-lower alkoxy, acyl, carboxy, esterified carboxy, amidated carboxy, cyano, carboxy-lower alkylamino, esterified carboxy-lower alkylamino, amidated carboxy-lower alkylamino, phosphono-lower alkylamino, esterified phosphono-lower alkylamino, nitro, amino, lower alkylamino, di-lower alkylamino, acylamino, N-acyl-N-lower alkylamino, phenylamino, phenyl-lower alkylamino, cycloalkyl-lower alkylamino or heteroaryl-lower alkylamino each of which may be unsubstituted or lower alkyl-lower alkoxy-, halo- and/or trifluoromethyl-substituted,
- in free form or in the form of a photoaffinity ligand, a radioactive marker, an N-oxide or a pharmaceutically acceptable salt.
Dependencies are inferred from the claim text.