New dipyrido-pyrrole compounds are protein kinase inhibitors useful for the treatment of cancer

摘要

Dipyrido-pyrrole compounds (I) are new. Dipyrido-pyrrole compounds of formula (I) are new. Z 2>-Z 4> : C or N; R 3> : (hetero)aryl, C(O)Oalkyl or 1-10C alkyl optionally comprising heteroatom (all optionally mono, di or tri substituted), H, halo (F, Cl, Br, I), CF 3, CHF 2, OH, NH 2, CONH(alkyl), CON(alkyl) 2, alkoxy, NH(alkyl), or N(alkyl) 2(in which all the alkyl part is in CONH(alkyl), CON(alkyl) 2, alkoxy, NH(alkyl), or N(alkyl) 2are optionally mono, di or tri substituted); R 6> : heteroaryl (5 or 6 membered ring with 1-4 heteroatoms of N, S or O) connected to azacarboline unit, C or N of R 6>, where R 6>is optionally mono or polysubstituted; either R1a : CON(alkyl) 2, CONHalkyl, CONHcycloalkyl, CONHheterocycloalkyl or CON(alkyl)(heterocycloalkyl) (all optionally mono, di or tri substituted), CONHN(alkyl) 2(in which alkyl part is optionally mono, di or tri substituted) or CONH 2; and R1s : O-1-10C alkyl, N(1-10C alkyl or 3-7C cycloalkyl) 2(all optionally mono or polysubstituted), H, Cl, Br, I, OH, NH 2, NHCOR3a, N-1-10C alkylCOR3a, NHSO 2R3a, N-1-10C alkylSO 2R3a, CO 2R3a, SR3a, SOR3a or SO 2R3a; or R1aR1s : ring. [Image] ACTIVITY : Cytostatic. MECHANISM OF ACTION : Protein kinase inhibitor. The ability of (I) to inhibit Proto-oncogene serine/threonine-protein 2 (Pim 2) kinase was tested using time resolved-fluorescence resonance energy transfer assays. The result showed that N-cyclopropyl-4-[3-fluoro-6-(pyridin-3-yl)-9H-pyrrolo[2,3-b:5,4-c']dipyridin-4-yl]benzamide exhibited an IC 5 0value of 1-5 mu M.