New 5'-biphenyl substituted cyclic ketoenol compounds are acetyl-coenzyme A carboxylase 1 inhibitors, useful for treating cancer e.g. breast cancer, pancreatic cancer, renal cell carcinoma, hepatocellular carcinoma and skin tumors

摘要

5'-Biphenyl substituted cyclic ketoenol compounds (I), are new. 5'-Biphenyl substituted cyclic ketoenol compounds of formula (I), are new. X : 1-3C alkyl or 1-3C alkoxy (both optionally substituted by at least a halo) or halo; W1, Y1 : H, halo or 1-3C alkyl (optionally substituted by at least a halo); either V1-V3 : H, halo, 1-3C (halo)alkyl, 1-3C (halo)alkoxy or 1-3 alkoxy-1-3C; or C+V1+V2 : optionally saturated and optionally at least a further heteroatom containing 5 or 6 membered cycle T1 (optionally substituted by one or more halo and/or 1-3C alkyl); either A : 1-6C alkyl- or 1-6C alkoxy-1-6C alkyl (both optionally substituted by at least a halo), 3-7C cycloalkyl or 4- to 7-membered monocyclic heterocyclyl (both optionally substituted by one or more halo and/or 1-3C alkyl) or H; and B1 : H, 1-6C alkyl or 1-3C alkoxy-1-3C alkyl; and D1 : 1-6C alkyl, 1-6C alkoxy-1-6C alkyl, 3-7C cycloalkyl or 4- to 7-membered monocyclic heterocyclyl (all optionally substituted by one or more halo, OH, 1-3C alkyl, halo-1-3C alkyl, 1-3C alkoxy, halo-1-3C alkoxy and/or 1-3C alkoxy-1-3C alkyl) or H; or C+A+B1 : optionally saturated, optionally one or two heteroatoms containing 3-8 membered cycle T2 (optionally substituted by one or more R1-R3); or A+D1 : optionally saturated and optionally a further heteroatom-containing 5-7 membered cycle T4 (optionally substituted by one or more R7-R9); R7-R9 : halo, 1-3C alkyl or 1-3C alkoxy; either R1-R3 : 1-4C alkyl, 1-4C alkoxy, 1-3C alkoxy-1-3C alkyl, 1-3C alkoxy-1-3C alkoxy, halo-1-3C-alkyl or halo-1-3C alkoxy (all optionally substituted by OH in alkyl residue), halo or OH; or two of R1-R3 together with cycle T2 : saturated or aromatic, optionally one or two heteroatoms containing 5-7 membered cycle T3 (optionally substituted by one or more R4-R6); and R4-R6 : 1-3C alkyl or 1-3C alkoxy. [Image] ACTIVITY : Cytostatic; Antipsoriatic; Vulnerary. MECHANISM OF ACTION : Acetyl-coenzyme A carboxylase 1 inhibitor; Acetyl-coenzyme A carboxylase 2 inhibitor. The ability of (I) to inhibit acetyl-coenzyme A carboxylase 2 was tested in vitro. The results showed that 3-(4'-chloro-4,6-dimethylbiphenyl-3-yl)-4-hydroxy-8-methoxy-1-azaspiro[4.5]dec-3-en-2-one exhibited an IC 50value of 0.087 mu ole/l.