| US 7,465,736 B2 | ||
| Azole methylidene cyanide derivatives and their use as protein kinase modulators | ||
| Pascale Gaillard, St-Julien-en-Genevois (France); Jean-Pierre Gotteland, Beaumont (France); Isabelle Jeanclaude-Etter, Bellevue (Switzerland); Matthias Schwarz, Geneva (Switzerland); and Russel J. Thomas, Siena (Italy) | ||
| Assigned to Laboratoires Serono S.A., Coinsins (Switzerland) | ||
| Appl. No. 10/516,330 PCT Filed Jun. 13, 2003, PCT No. PCT/EP03/50225 § 371(c)(1), (2), (4) Date Sep. 22, 2005, PCT Pub. No. WO03/106455, PCT Pub. Date Dec. 24, 2003. |
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| Claims priority of application No. 02100710 (EP), filed on Jun. 14, 2002. | ||
| Prior Publication US 2007/0123530 A1, May 31, 2007 | ||
| Int. Cl. C07D 417/06 (2006.01); C07D 417/08 (2006.01); C07D 417/14 (2006.01); A61K 31/427 (2006.01); A61P 3/04 (2006.01); A61P 3/10 (2006.01); C07D 413/06 (2006.01); C07D 413/14 (2006.01); A61K 31/4523 (2006.01); A61K 31/497 (2006.01); A61K 31/502 (2006.01) | ||
| U.S. Cl. 514—256 [514/258.1; 514/269; 514/274; 514/275; 514/252.01; 514/252.1; 514/336; 544/253; 544/299; 544/323; 544/326; 544/333; 544/334; 544/335; 544/238; 544/239; 544/240; 544/241; 544/336] | 18 Claims |
1. An azole compound according to formula (I),
 a tautomer thereof, a geometrical isomer thereof, an optically active form thereof as an enantiomer thereof, a diastereomer
thereof, a racemate form thereof, or a pharmaceutically acceptable salt thereof, wherein
X is S;
A is a pyrimidinyl, which may be substituted with 1, 2 or 3 moieties R2 and/or fused with an aryl or a heteroaryl group;
R0 is selected from the group consisting of hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-alkyl-aryl, aryl, heteroaryl, C1-C6-alkyl-heteroaryl, —C(O)—OR5, —C(O)—R5, —C(O)—NR5R5′, and —(SO2)R5, wherein R5 and R5′, being independently selected from the group consisting of hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, aryl, heteroaryl, C1-C6-alkyl aryl, and C1-C6-alkyl heteroaryl;
R1 is selected from the group consisting of hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-alkoxy, C1-C6-sulfanyl, primary, secondary or tertiary amino groups, aminoacyl, aminocarbonyl, C1-C6 alkoxycarbonyl, C3-C8-cycloalkyl, C3-C8 heterocycloalkyl, aryl, heteroaryl, carboxyl, cyano, halogen, hydroxy, nitro, sulfonamide and hydrazide;
R2 is selected from the group consisting of hydrogen, sulfonyl, amino, C1-C6-alkyl, C2-C6-alkenyl, and C2-C6-alkynyl, wherein said alkyl, alkenyl, alkynyl chains may be interrupted by a heteroatom selected from the group consisting
of N, O, S, aryl, heteroaryl, saturated or unsaturated 3-8-membered cycloalkyl, and heterocycloalkyl, wherein said cycloalkyl,
heterocycloalkyl, aryl or heteroaryl groups may be fused with 1-2 further cycloalkyl, heterocycloalkyl, aryl or heteroaryl
group, an acyl moiety, C1-C6-alkyl aryl, C1-C6-alkyl heteroaryl, C1-C6-alkenyl aryl, C1-C6-alkenyl heteroaryl, C1-C6-alkynyl aryl, C1-C6-alkynyl heteroaryl, C1-C6-alkyl cycloalkyl, C1-C6-alkyl heterocycloalkyl, C1-C6-alkenyl cycloalkyl, C1-C6-alkenyl heterocycloalkyl, C1-C6-alkynyl cycloalkyl, C1-C6-alkynyl heterocycloalkyl, alkoxycarbonyl, aminocarbonyl, C1-C6-alkyl carboxy, C1-C6-alkyl acyl, aryl acyl, heteroaryl acyl, C3-C8-(hetero)cycloalkyl acyl, C1-C6-alkyl acyloxy, C1-C6-alkyl alkoxy, C1-C6-alkyl alkoxycarbonyl, C1-C6-alkyl aminocarbonyl, C1-C6-alkyl acylamino, acylamino, C1-C6-alkyl ureido, C1-C6-alkyl carbamate, C1-C6-alkyl amino, C1-C6-alkyl ammonium, C1-C6-alkyl sulfonyloxy, C1-C6-alkyl sulfonyl, C1-C6-alkyl sulfinyl, C1-C6-alkyl sulfanyl, C1-C6-alkyl sulfonylamino, C1-C6-alkyl aminosulfonyl, hydroxy or halogen,
wherein the following compounds are excluded:
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