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US 2004/0171633 A1Published application
(1, 8) naphthyridines as gaba ligands, their pharmaceutical compositions and uses
AssigneeMerck Sharp & Dohme Corp.
InventorsWilliam Robert Carling, Andrew Mitchinson, Michael Geoffrey Russell, Leslie Joseph Street
Life of this patent
Estimating the term…
Abstract
A class of [1,8] naphthyridine analogues which are substituted in the 4-position by a substituted phenyl ring. These compounds are ligands for GABAA receptors and useful in the therapy of deleterious mental states such as anxiety.
Claims10
A compound of formula I or a pharmaceutically acceptable salt thereof:
- 13
- wherein
- X represents hydrogen or halogen;
- Y represents a chemical bond, an oxygen atom, or a —NH— linkage;
- Z represents an optionally substituted aryl or heteroaryl group;
- R1 represents hydrogen, hydrocarbon, a heterocyclic group, halogen, cyano, trifluoromethyl, nitro, —ORa, —SRa, —SORa, —SO2Ra, —SO2NRaRb, —NRaRb, —NRaCORb, —NRaCO2Rb, —CORa, —CO2Ra, —CONRaRb, —CRa═NORb or CRa═NNHRb.
3 more elements
A compound selected from:
- 3′-(7-methyl-[1,8]naphthyridin-4-yl)biphenyl-2-carbonitrile;
- 2′-fluoro-5′-(7-methyl-[1,8]naphthyridin-4-yl)biphenyl-2-carbonitrile;
- 6,2′-difluoro-5′-(7-trifluoromethyl[1,8]naphthyridin-4-yl)biphenyl-2-carbonitrile;
- 5-(4-fluoro-3-pyridin-3-ylphenyl)-2-trifluoromethyl[1,8]naphthyridine;
- 5-(4-fluoro-3-pyridin-4-ylphenyl)-2-trifluoromethyl[1,8]naphthyridine;
- 5-[4-fluoro-3-(3-fluoropyridin-2-yl)phenyl]-2-trifluoromethyl[1,8]naphthyridine;
- 3,2′-difluoro-5′-(7-trifluoromethyl-[1,8]naphthyridin-4-yl)biphenyl-2-carbonitrile;
- 4,2′-difluoro-5′-(7-trifluoromethyl-[1,8]naphthyridin-4-yl)biphenyl-2-carbonitrile;
- 5,2′-difluoro-5′-(7-trifluoromethyl-[1,8]naphthyridin-4-yl)biphenyl-2-carbonitrile;
- 4-fluoro-3′-(7-trifluoromethyl[1,8]naphthyridin-4-yl)biphenyl-2-carbonitrile;
- 5-(2-fluoro-3-pyridin-2-ylphenyl)-2-trifluoromethyl-[1,8]naphthyridine;
- 5-(2-fluoro-3-pyridin-3-ylphenyl)-2-trifluoromethyl-[1,8]naphthyridine;
- 5-(2-fluoro-3-pyridin-4-ylphenyl)-2-trifluoromethyl-[1,8]naphthyridine;
- 5-(2,4-difluoro-3-pyridin-3-ylphenyl)-2-trifluoromethyl[1,8]naphthyridine;
- 5-(2,4-difluoro-3-pyridin-4-ylphenyl)-2-trifluoromethyl[1,8]naphthyridine;
- 3′-fluoro-5′-(7-trifluoromethyl-[1,8]naphthyridin-4-yl)biphenyl-2-carbonitrile;
- 2′-fluoro-5′-(7-trifluoromethyl-[1,8]naphthyridin-4-yl)biphenyl-3-carbonitrile;
- 2′-fluoro-5′-(7-trifluoromethyl[1,8]naphthyridin-4-yl)biphenyl-4-carbonitrile;
- 5-(6-fluoro-2′-methanesulfonylbiphenyl-3-yl)-2-trifluoromethyl[1,8]-naphthyridine;
- 5-(3′-methoxybiphenyl-3-yl)-2-trifluoromethyl[1,8]naphthyridine;
- 5-[4-fluoro-3-(3-fluoropyridin-4-yl)phenyl]-2-trifluoromethyl[1,8]naphthyridine;
- 2-[2-fluoro-5-(7-trifluoromethyl[1,8]naphthyridin-4-yl)phenyl]nicotinonitrile;
- 2-[2-fluoro-5-(7-trifluoromethyl[1,8]naphthyridin-4-yl)phenyl]nicotinamide;
- 5-(3-fluoro-5-pyridin-3-ylphenyl)-2-trifluoromethyl[1,8]naphthyridine;
- 5-(4-fluoro-3-pyrimidin-4-ylphenyl)-2-trifluoromethyl[1,8]naphthyridine;
- 5-[3-(2-methyl-2H-tetrazol-5-yl)phenyl]-2-trifluoromethyl[1,8]naphthyridine;
- 5-(3-furan-2-ylphenyl)-2-trifluoromethyl[1,8]naphthyridine;
- 5-[3-(pyridin-2-ylmethoxy)phenyl]-2-trifluoromethyl[1,8]naphthyridine;
- 5-(4-fluoro-3-morpholin-4-ylmethylphenyl)-2-trifluoromethyl[1,8]naphthyridine;
- 5-[3-(3,5-difluoropyridin-2-yl)-4-fluorophenyl]-2-trifluoromethyl[1,8]-naphthyridine;
- 2′-fluoro-5′-(7-trifluoromethyl[1,8]naphthyridin-4-yl)biphenyl-2-carbonitrile;
- 5-(4-fluoro-3-pyridin-2-yl)-2-trifluoromethyl[1,8]naphthyridine;
- 6,2′-difluoro-5′-(7-trifluoromethyl[1,8]naphthyridin-4-yl)biphenyl-3-carbonitrile;
- 5-(4-fluoro-3-methoxyphenyl)-2-trifluoromethyl[1,8]naphthyridine;
- 5-(3′-chloro-6-fluorobiphenyl-3-yl)-2-trifluoromethyl[1,8]naphthyridine;
- N-[2′-fluoro-5′-(7-trifluoromethyl[1,8]naphthyridin-4-yl)biphenyl-3-yl]acetamide;
- 1-[2′-fluoro-5′-(7-trifluoromethyl[1,8]naphthyridin-4-yl)biphenyl-3-yl]ethanone;
- 5-(6-fluoro-2′-methoxybiphenyl-3-yl)-2-trifluoromethyl[1,8]naphthyridine;
- 5-(6-fluoro-2′-trifluoromethylbiphenyl-3-yl)-2-trifluoromethyl[1,8]naphthyridine;
- 5-(4-fluoro-3-pyrimidin-5-ylphenyl)-2-trifluoromethyl[1,8]naphthyridine;
- 5-(4-fluoro-3-quinolin-6-ylphenyl)-2-trifluoromethyl[1,8]naphthyridine;
- 5-(4-fluoro-3-thiazol-2-ylphenyl)-2-trifluoromethyl[1,8]naphthyridine;
- 5-(4-fluoro-3-pyrazin-2-ylphenyl)-2-trifluoromethyl[1,8]naphthyridine;
- 5-(4-fluoro-3-trifluoromethylphenyl)-2-trifluoromethyl[1,8]naphthyridine;
- 2-fluoro-5-(7-trifluoromethyl[1,8]naphthyridine-4-yl)benzonitrile;
- 2-[6-(7-trifluoromethyl[1,8]naphthyridin-4-yl)pyridin-2-yl]benzonitrile;
- 5-[4-fluoro-3-(pyridin-3-ylmethoxy)phenyl]-2-trifluoromethyl[1,8]naphthyridine;
- 5-[4-fluoro-3-(pyridin-4-ylmethoxy)phenyl]-2-trifluoromethyl[1,8]naphthyridine;
- 5-[4-fluoro-3-(pyridin-2-yloxy)phenyl]-2-trifluoromethyl[1,8]naphthyridine;
- [2-fluoro-5-(7-trifluoromethyl[1,8]naphthyridin-4-yl)phenoxy]acetonitrile;
- 2-[2-fluoro-5-(7-trifluoromethyl[1,8]naphthyridin-4-yl)phenoxy]-N,N-dimethylacetamide;
- 5-[4-fluoro-3-(2-methyl-2H-[1,2,4]triazol-3-ylmethoxy)phenyl]-2-trifluoromethyl[1,8]naphthyridine;
- 5-[4-fluoro-3-(1-methyl-1H-[1,2,3]triazol-4-ylmethoxy)phenyl]-2-trifluoromethyl[1,8]naphthyridine;
- 5-(4-fluorophenyl)-2-trifluoromethyl[1,8]naphthyridine;
- 2′-fluoro-5′-[7-(2-fluorophenyl)-[1,8]naphthyridin-4-yl]biphenyl-2-carbonitrile;
- 2′-fluoro-5′-[7-(pyridin-3-yl)-[1,8]naphthyridin-4-yl]biphenyl-2-carbonitrile;
- 2′-fluoro-5′-[7-(thiazol-2-yl)-[1,8]naphthyridin-4-yl]biphenyl-2-carbonitrile;
- 5′-[7-acetyl-[1,8]naphthyridin-4-yl]-2′-fluorobiphenyl-2-carbonitrile;
- 2′-fluoro-5′-[7-(1-hydroxy-1-methylethyl)-[1,8]naphthyridin-4-yl]biphenyl-2-carbonitrile;
- or a pharmaceutically acceptable salt thereof.
57 more elements
Dependencies are inferred from the claim text.