Substituted piperazine compounds and their use as fatty acid...

C - Chemistry – Metallurgy – 07 – D

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C07D 417/12 (2006.01) A61K 31/496 (2006.01) A61P 3/10 (2006.01) A61P 9/00 (2006.01) C07D 263/56 (2006.01) C07D 263/57 (2006.01) C07D 271/06 (2006.01) C07D 277/64 (2006.01) C07D 413/04 (2006.01) C07D 413/12 (2006.01) C07D 413/14 (2006.01) C07D 417/14 (2006.01)

Patent

CA 2454059

Disclosed are novel heterocyclic derivatives of the formula (I), wherein amongst others R1, R2, R3, R4, R5, R6, R7, and R8 are hydrogen; T is oxygen, sulfur, or NR11, in which R11 is hydrogen or lower alkyl; V is N<, -CH<, or N- CH<; X1 is hydrogen, optionally substituted lower alkyl, optionally substituted cycloalkyl, optionally substituted aryl, or optionally substituted heteroaryl; X2 is optionally substituted aryl or optionally substituted heteroaryl; Y is optionally substituted monocyclic heteroarylenyl; and Z1 and Z2 are independently optionally substituted alkylene or 1-4 carbon atoms. The compounds are useful for the treatment of various disease states, in particular cardiovascular diseases such as atrial and ventricular arrhythmias, intermittent claudication, Prinzmetal's (variant) angina, stable and unstable angina, exercise induced angina, congestive heart disease, and myocardial infarction. The compounds are also useful in the treatment of diabetes, and for increasing HDL plasma levels in mammals.

L'invention concerne de nouveaux dérivés hétérocycliques de la formule (I) dans laquelle, entre autres, R?1¿, R?2¿, R?3¿, R?4¿, R?5¿, R?6¿, R?7¿ et R?8¿ représentent hydrogène; T représente oxygène, soufre ou NR?11¿, où R?11¿ représente hydrogène ou alkyle inférieur; V représente -N<, -CH< ou -N-CH<; X?1¿ représente hydrogène, alkyle inférieur facultativement substitué, cycloalkyle facultativement substitué, aryle facultativement substitué ou hétéroaryle facultativement substitué; X?2¿ représente aryle facultativement substitué ou hétéroaryle facultativement substitué; Y représente hétéroarylènyle monocyclique facultativement substitué; et Z?1¿ ainsi que Z?2¿ représentent indépendamment alkylène facultativement substitué ayant de 1 à 4 atomes de carbone. Les composés sont utiles dans le traitement de divers états pathologiques, notamment de maladies cardio-vasculaires telles que les arythmies auriculaires et ventriculaires, la claudication intermittente, l'angor de Prinzemtal (spastique), l'angor stable et instable, l'angor induit par l'exercice, les maladies cardiaques congestives et l'infarctus du myocarde. Les composés sont aussi utiles dans le traitement du diabète et pour augmenter les niveaux de HDL dans le plasma chez des mammifères.

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