| US 7,462,621 B2 | ||
| Use of substituted 2-pyridinyl-6,7,8,9-tetrahydropyrimido[1,2-a] pyrimidin-4-one and 7-pyridinyl-2,3-dihydroimidazo[1,2-a] pyrimidin-5(1H)one derivatives as therapeutic agents | ||
| Thierry Gallet, Palaiseau (France); Patrick Lardenois, Bourg-la-Reine (France); Alistair Lochead, Charenton le Pont (France); Severine Marguerie, Rennes (France); Alain Nedelec, Colombes (France); Mourad Saady, Paris (France); Franck Slowinski, Thieux (France); and Philippe Yaiche, Les Lilas (France) | ||
| Assigned to Sanofi-Aventis, Paris (France); and Mitsubishi Pharma Corporation, Osaka (Japan) | ||
| Filed on Apr. 05, 2007, as Appl. No. 11/696,982. | ||
| Application 11/696982 is a continuation of application No. 10/490135, filed on Sep. 07, 2004, granted, now 7,214,682. | ||
| Application 10/490135 is a continuation of application No. PCT/EP02/11128, filed on Sep. 19, 2002. | ||
| Claims priority of application No. 01402432 (EP), filed on Sep. 21, 2001; and application No. 02290489 (EP), filed on Feb. 28, 2002. | ||
| Prior Publication US 2007/0167461 A1, Jul. 19, 2007 | ||
| This patent is subject to a terminal disclaimer. | ||
| Int. Cl. C07D 487/04 (2006.01); A61K 31/519 (2006.01); A61P 25/28 (2006.01); A61K 31/55 (2006.01) | ||
| U.S. Cl. 514—259.5 [514/221; 544/279] | 8 Claims |
1. A method of inhibiting the activity of glycogen synthase kinase 3-beta (GSK3-β), which comprises administering to a patient
in need of said inhibition an effective amount of a compound of formula (I) or a physiologically acceptable salt thereof:
 X represents two hydrogen atoms, a sulfur atom, an oxygen atom or a C1-2 alkyl group and a hydrogen atom;
Y represents a bond, an ethenylene group, an ethynylene group, an oxygen atom, a sulfur atom, a sulfonyl group, a sulfoxide
group, a carbonyl group, a hydroxyiminomethylene group, a dioxolan group, a nitrogen atom being optionally substituted by
a C1-6 alkyl group, a phenyl group or a benzyl group; or a methylene group optionally substituted by one or two groups chosen from
a C1-6 alkyl group, a benzyl group, a hydroxyl group, a C1-4 alkoxy group, a C1-2 perhalogenated alkyl group, an amino group, an acetylamino group or a phenyl group;
R1 represents a 2, 3 or 4-pyridine ring optionally substituted by a C3-6 cycloalkyl group, a C1-4 alkyl group, a C1-4 alkoxy group, a benzyl group or a halogen atom;
when Y represents a bond, a methylene group optionally substituted, a hydroxylminomethylene group, a dioxolan group or a carbonyl
group then R2 represents a C1-6 alkyl group optionally substituted by a hydroxy group, a C6,10 aryloxy or a C6,10 arylamino group; a C3-6 cycloalkyl group, a C1-4 alkylthio group, a C1-4 alkoxy group, a C1-2 perhalogenated alkyl group, a C1-3 halogenated alkyl group, a phenylthio group, a benzyl group, a benzene ring, an indan ring, a 5,6,7,8-tetrahydronaphthalene
ring, a naphthalene ring, a pyridine ring, a pyrrole ring, a thiophene ring, a furan ring or an imidazole ring; the benzyl
group or the rings being optionally substituted by 1 to 4 substituents selected from a C1-6 alkyl group, a methylenedioxy group, a halogen atom, a C1-2 perhalogenated alkyl group, a C1-3 halogenated alkyl group, a hydroxyl group, a C1-4 alkoxy group, a nitro, a cyano, an amino, a C1-5 monoalkylamino group, a C2-10 dialkylamino group, a C1-6 alkylcarbonylamino group, a C6,10 arylcarbonylamino group, a C1-4 alkylsulfonyl group, C1-4 alkylsulfonyloxy group or a phenyl group;
when Y represents a ethenylene group, a ethynylene group, an oxygen atom, a sulfur atom, a sulfonyl group, a sulfoxide group
or a nitrogen atom being optionally substituted then R2 represents a C1-6 alkyl group optionally substituted by a hydroxy group, a C6,10 aryloxy or a C6,10 arylamino group; a C3-6 cycloalkyl group, a C1-2 perhalogenated alkyl group, a C1-3 halogenated alkyl group, a benzyl group, a benzene ring, an indan ring, a 5,6,7,8-tetrahydronaphthalene ring, a naphthalene
ring, a C6,10 arylamino, a pyridine ring, a pyrrole ring, a thiophene ring, a furan ring or an imidazole ring; the benzyl group or the rings
being optionally substituted by 1 to 4 substituents selected from a C1-6 alkyl group, a methylenedioxy group, a halogen atom, a C1-2 perhalogenated alkyl group, a C1-3 halogenated alkyl group, a hydroxyl group, a C1-4 alkoxy group, a nitro, a cyano, an amino, a C1-5 monoalkylamino group, a C2-10 dialkylamino group, a C1-6 alkylcarbonylamino group, a C6,10 arylcarbonylamino group, a C1-4 alkylsulfonyl group, C1-4 alkylsulfonyloxy group or a phenyl group;
R3 represents a hydrogen atom, a C1-6 alkyl group, a hydroxy group, a C1-4 alkoxy group or a halogen atom;
R4 represents a hydrogen atom, a C1-6 alkyl group, a hydroxy group, a C1-4 alkoxy group or a halogen atom;
R5 represents a hydrogen atom, a C1-6 alkyl group or a halogen atom; with the proviso that when R3 and R4 represent each a hydrogen atom then R5 is not a hydrogen
atom;
when m equals 0, p equals 1, 2 or 3,
when m equals 1, p equals 0, 1 or 2,
when m equals 2, p equals 0 or 1 ; and
n represents 0 to 3.
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