HETEROCYCLIC COMPOUNDS AND METHODS TO TREAT CARDIAC FAILURE AND OTHER DISORDERS

• Main Authors: LIU, DAVID Y, SCHREINER, GEORGE F, MAVUNKEL, BABU J, LEWICKI, JOHN A, PERUMATTAM, JOHN J
• Format: Patent
• Language: English; French
• Published: 02.12.1999
• Edition: 6
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

Compounds of formulae .alpha. or .beta., and the pharmaceutically acceptable salts thereof, wherein each of Z1 and Z2 is independently CR4 or N; where ea ch 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, NR2, 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 containi ng 1-2 heteroatoms; R1 is formula (I); wherein X1 is CO or an isostere thereof; m is 0 or 1; Y is optionally substituted alkyl, optionally substituted aryl, o r optionally substituted arylalkyl or two Y taken together may form an alkylen e (2-3C) bridge; n is 0 or 2; Z3 is CH or N; X2 is CH, CH2 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 CF3, 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; R2 is H, or is alkyl(1-6C) or aryl, each or said alk yl or aryl optionally including one heteroatome which is O, S or N, and optionally substituted by one or more of halo, OR, SR, NR2, 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; R3 is H, halo, NO2, 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 selecti ve inhibitors of p38.alpha. kinase.