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EP1080078A1 HETEROCYCLIC COMPOUNDS AND METHODS TO TREAT CARDIAC FAILURE AND OTHER DISORDERS 有权
HETEROZYCLISCHE衍生物对心力衰竭等疾病的治疗

HETEROCYCLIC COMPOUNDS AND METHODS TO TREAT CARDIAC FAILURE AND OTHER DISORDERS
摘要:
Compounds of formulae α or β, and the pharmaceutically acceptable salts thereof, wherein each of Z?1 and Z2¿ is independently CR4 or N; where each R4 is independently H or is alkyl (1-6C) or aryl, each of said alkyl or aryl optionally including one or more heteroatoms selected from O, S and N and optionally substituted by one or more of halo, OR, SR, NR¿2?, RCO, COOR, CONR2, OOCR, or NROCR where R is H or alkyl (1-6C), or by one or more CN or =O, or by one or more aliphatic or aromatic 5- or 6-membered rings optionally containing 1-2 heteroatoms; R?1¿ is formula (I); wherein X1 is CO or an isostere thereof; m is 0 or 1; Y is optionally substituted alkyl, optionally substituted aryl, or optionally substituted arylalkyl or two Y taken together may form an alkylene (2-3C) bridge; n is 0 or 2; Z3 is CH or N; X2 is CH, CH¿2? or an isostere thereof; and Ar consists of one or two phenyl moieties directly coupled to X?2¿ optionally substituted by halo, nitro, alkyl(1-6C), alkenyl(1-6C), alkynyl(1-6C), CN or CF¿3?, or by RCO, COOR, CONR2, NR2, OR, SR, OOCR or NROCR wherein R is H or alkyl(1-6C) or by phenyl, itself optionally substituted by the foregoing substituents; R?2¿ is H, or is alkyl(1-6C) or aryl, each or said alkyl or aryl optionally including one heteroatome which is O, S or N, and optionally substituted by one or more of halo, OR, SR, NR¿2?, RCO, COOR, CONR2, OOCR, or NROCR where R is H or alkyl(1-6C), alkynyl(1-6C), or by one or more CN or =O, or by one or more aliphatic or aromatic 5- or 6-membered rings optionally containing 1-2 heteroatoms; R?3¿ is H, halo, NO¿2?, alkyl(1-6C), alkenyl(1-6C), alkynyl(1-6C), CN, OR, SR, NR2, RCO, COOR, CONR2, OOCR, or NROCR where R is H or alkyl(1-6C) are disclosed. These compounds are selective inhibitors of p38α kinase.
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