Chk1 inhibitors aryl and heteroaryl urea-urea for use as radiosensitizers and chemosensitizers.

摘要

A compound having a formula ** ** Formula or pharmaceutically acceptable salt or solvate thereof, wherein Y 'is O or S; W 'is selected from the group consisting of Formula ** ** and optionally substituted with one to four substituents selected from the group consisting of C1- 6 alkyl, aryl, N (R7) 2, O7, N3, CN, C (O) R7, C1-3 alkylene-aryl, C1-3 alkylene-N (R12) 2, C1-3 alkylene and halo; Z '' is selected from the group consisting of: ** ** Formula and wherein: Q 'is selected from the group consisting of hydro, OR7, SR7, and N (R7) 2, with the proviso that Q 'is hydro only when at least one of J', K ', L', and M 'is N, O, or S; J 'is selected from the group consisting of CR8, NR8, O and S; K 'is selected from the group consisting of CR9, NR9, O and S; L 'is selected from the group consisting of CR10, NR10, O and S; M '' is selected from the group consisting of CR11, NR11, O and S; wherein: R7, independently, is selected from the group consisting of hydro, C1-6alkyl, C2-6alkenyl, cycloalkyl, aryl, heteroaryl, SO2R12, C1-6alkyl substituted with one or more halo, hydroxy , aryl, heteroaryl, heterocycloalkyl, N (R12) 2 and SO2R12, C1-3 alkylene-aryl, C1-3 alkylene-heteroaryl, C 1-3 heterocycloalkyl alkylene 3-8, C1-3 alkylene-SO2-aryl, C1 -3-N (R12) 2, OCF3, alkylene C1-3N (R12) 3+, C3-8heterocycloalkyl, and CH (alkylene C1-3N (R12) 2) 2, or two R7 groups are taken together to form an aliphatic ring of 3 to 6 membered optionally substituted; R8, R9 and R10 are each independently selected from the group consisting of null, hydro, halo, optionally substituted C1-6 alkyl, C2-6 alkenyl optionally substituted, OCF3, NO2, CN, NC, N (R7) 2 , OR7, CO2R7, C (O) N (R7) 2, C (O) R7, N (R13) COR7, N (R13) C (O) OR7, N (R7) C (O) OR7, N (R7 ) C (O) C1-3 alkylene-C (O) R7, N (R7) C (O) C1-3 alkylene-C (O) OR7, N (R7) C (O) C1-3 alkylene-OR7, N (R7) C (O) C1-3 alkylene-NHC (O) OR7, N (R7) C (O) C1-3 alkylene-SO2NR7, CF3, C1-3 alkylene-N (R12) SO2-aryl, alkylene 1-3C-N (R12) SO2-heteroaryl, C1-3 alkylene-O-C1-3 alkylene-aryl, C1-3 alkylene-N (R12) C1-3 alkylene-aryl, C1-3 alkylene-N (R12 ) -C 1-3 alkyl-heteroaryl, C1-3 alkylene-N (R12) C (O) R7, C1-3 alkylene-N (R12) C (O) C1-3 alkylene-OR2, C1-3 alkylene-N (R12) C (O) -aryl, C1-3 alkylene-N (R12) C (O) C1-3 alkylene-N (R12) 2, C1-3 alkylene-N (R12) C (O) heteroaryl, alkylene OR7 and SR7 C 1-3, in which R7 is as defined above; R11 is selected from the group consisting of null, hydro, optionally substituted C1-6 alkyl and halo; SO2-C1-6 alkyl R12 is selected from the group consisting of hydro, C1-6alkyl, cycloalkyl, aryl, heteroaryl, C1-3 alkylenearyl, and alkyl, or two R12 groups are taken together to form a ring of 3 to 6 membered optionally substituted; and R13 is selected from the group consisting of hydro, C1-6alkyl, C2-6 alkenyl, C2-66 alkynyl and aryl; provided that when Q 'is hydro or OCH3, at least one of R8, R9 and R10 is different from hydro, CH3, OCH3 and halo; and provided that the compound is not N- [6- (bencilpirid-2yl)] - N '- (2-pyrazinyl) thiourea.