Pirazolil acilsulfonamidas as Endothelin converting Enzyme inhibitors useful in the treatment of chronic obstructive pulmonary disease

摘要

Claim 1: A compound characterized in that it is of formula (1) where: R1 is optionally substituted aryl or optionally substituted heteroaryl; R2 and R4 independently represent H, halogen, C1-6 alkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, or C3-7 cycloalkyl [optionally substituted by halogen or C1 -4 alkyl]; R3 is optionally substituted aryl, optionally substituted heteroaryl, or C3-7 cycloalkyl [optionally substituted by halogen or C1-4alkyl]; the aryl and heteroaryl portions are optionally independently substituted with one or more dehalogen, cyano, nitro, OC (O) NR5R6, NR7R8, NR10C (O) NR11R12,S (O) 2NR13R14, NR15S (O) 2R16, C (O) NR17R18, CO2R19, NR20CO2R21, S (O) nR22, OS (O) 2R23, C1-6 alkyl (optionally monosubstituted with S (O) 2R24 or C ( O) NR25R26),C (O) R27, NR28C (O) R29, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C1-6 haloalkyl, C1-6 alkoxy (C1-69alkyl, C1-6 alkoxy, C1-6 hydroxyalkyl , C1-6 haloalkoxy, phenyl, phenyl (C1-4) alkyl, phenoxy, phenylthio, phenylS (O),Fenils (o) 2, fenil (C1-4) alcoxi, heaterilo, heateril (C1-4) acoxi, heateriloloxi or heaterial (C1-4) alcoxi; in these places, the newly mentioned phenyl and heteromorphic parts are replaced by halogen, nitro, NH2, NH (C1-4) tar,N (C1-4 tar) 2, s (C1-4 tar),S (o) (C1-4 tar)S (o) 2 (C1-4 tar) s (o) 2nh2, s (o) 2nh (C1-4 tar),S (O) 2N (C1-4alkyl) 2, cyano, C1-4alkyl, C1-4alkoxy, C (O) NH2, C (O) NH (C1-4alkyl),C (o) n (C1-4 tar) 2, CO2H, CO2 (C1-4 tar),NHC (o) (C1-4 tar)NHS (o) 2 (C1-4 tar),C (o) (C1-4 tar)CF3 or OCF3; R5, R6, R7, R8, R10, R11, R12, R13, R14, R15, R17, R18, R19, R20, R21, R25, R26, R27, R28 and R29 are independently H, C1-6 alkyl [optionally substituted with halogen, C3-6 cycloalkyl or phenyl {optionally substituted with halogen or C1-4 alkyl}], CH2 (C2-6 alkenyl),Phenyl [substituted halide, nitro, NH2, NH (C1-4 tar),N (C1-4 tar) 2, s (C1-4 tar),S (o) (C1-4 tar)S (o) 2 (C1-4 tar) s (o) 2nh2, s (o) 2nh (C1-4 tar),S (O) 2N (C1-4alkyl) 2, cyano, C1-4alkyl, C1-4alkoxy, C (O) NH2, C (O) NH (C1-4alkyl),C (o) n (C1-4 tar) 2, CO2H, CO2 (C1-4 tar),NHC (o) (C1-4 tar)NHS (o) 2 (C1-4 tar),C (o) (C1-4 tar)CF3 or ocf3) or heteromorphic [alternative halogen, nitro, NH2, NH (C1-4 tar),N (C1-4 tar) 2, s (C1-4 tar),S (o) (C1-4 tar)S (o) 2 (C1-4 tar) s (o) 2nh2, s (o) 2nh (C1-4 tar),S (O) 2N (C1-4alkyl) 2, cyano, C1-4alkyl, C1-4alkoxy, C (O) NH2, C (O) NH (C1-4alkyl),C (o) n (C1-4 tar) 2, CO2H, CO2 (C1-4 tar),NHC (o) (C1-4 tar)NHS (o) 2 (C1-4 tar),C (o) (C1-4 tar)C3 or ocf3]; R16, R22, R23 and R24 are C1-6 tar [substitute halogen, C3-6 cyclododecane or phenyl (substitute halogen or C1-4 tar)], CH2 (c2-6 alquenilo),Phenyl [substituted halide, nitro, NH2, NH (C1-4 tar),N (C1-4 tar) 2, s (C1-4 tar),S (o) (C1-4 tar)S (o) 2 (C1-4 tar) s (o) 2nh2, s (o) 2nh (C1-4 tar),S (O) 2N (C1-4alkyl) 2, cyano, C1-4alkyl, C1-4alkoxy, C (O) NH2, C (O) NH (C1-4alkyl),C (o) n (C1-4 tar) 2, CO2H, CO2 (C1-4 tar),NHC (o) (C1-4 tar)NHS (o) 2 (C1-4 tar),C (o) (C1-4 tar)CF3 or ocf3) or heteromorphic [alternative halogen, nitro, NH2, NH (C1-4 tar),N (C1-4 tar) 2, s (C1-4 tar),S (o) (C1-4 tar)S (o) 2 (C1-4 tar) s (o) 2nh2, s (o) 2nh (C1-4 tar),S (O) 2N (C1-4alkyl) 2, cyano, C1-4alkyl, C1-4alkoxy, C (O) NH2, C (O) NH (C1-4alkyl),C (o) n (C1-4 tar) 2, CO2H, CO2 (C1-4 tar),NHC (o) (C1-4 tar)NHS (o) 2 (C1-4 tar),C (o) (C1-4 tar)Moreover, n is 0, 1 or 2; or acceptable salt for pharmaceutical use.