Quinoline and cinnoline derivatives and their applications

摘要

The present invention relates to a series of quinoline and cinnoline derivatives of general formula I, pharmaceutically acceptable salts, hydrates, solvates or prodrugs thereof. And the compounds of general formula I show potent inhibitory activity gainst c-Met kinase. The present invention further relates to the uses of the compounds, pharmaceutically acceptable salts and hydrates for the preparation of medicaments for the treatment and/or prevention of diseases caused by abnormal expression of c-Met kinase, especially for treatment and/or prevention of cancer.;

主权项

1. A compound of formula I or a pharmaceutically acceptable salt, hydrate, solvate or prodrug thereof,wherein:
P is F or H; X is O, S, NH or NCH3; Z is N or CH; Y is N or CH; n is an integer between 1 and 6; R1 and R2, which are same or different, are selected independently from the group consisting of H, (C1-C10) alkyl, (C3-C7) cycloalkyl, (C2-C10)alkenyl and (C2-C10)alkynyl, wherein said alkyl, cycloalkyl, alkenyl and alkynyl are optionally substituted with 1 to 3 same or different R4; or R1 and R2 are covalently bonded together with the nitrogen to which they are attached to form 5- to 10-membered heterocyclic radical or 5- to 10-membered heteroaryl radical, said heterocyclic radical or heteroaryl radical may have optionally 1 to 4 heteroatoms selected from N, O, and S except the nitrogen atom to which R1 and R2 are attached, said heterocyclic radical may optionally have 1 to 2 carbon-carbon double bond or triple bond, said heterocyclic and heteroaryl radicals can be optionally substituted with 1 to 3 same or different R4; R4 is (C1-C4) alkyl, (C1-C4)alkoxyl, halogen, hydroxyl, cyano, carboxyl, or an ester group; R3 is hydrogen or 1 to 3 substituents selected independently from the group consisting of hydroxyl, halogen, nitro, amino, cyano, (C1-C6) alkyl, (C2-C6) alkenyl, (C2-C6) alkynyl, (C1-C6) alkoxyl, (C1-C6) alkylsulfanyl, (C1-C6) alkyl or (C1-C6) alkoxyl or (C1-C6) alkylsulfanyl substituted optionally with hydroxyl, amino or halogen, amino substituted with 1 or 2 (C1-C6) alkyl, (C1-C6)alkylamido, carboxy group which can be free, salts, or form ester group, (C1-C6) alkylsulfinyl, sulfonyl, (C1-C6)alkylacyl, aminoformyl, aminoformyl substituted with 1 or 2 (C1-C6)alkyl, and (C1-C3)alkylenedioxo; Ar represents (C6-C10) aryl, or 5- to 10-membered heteroaryl radical, wherein said heteroaryl radical may have 1 to 3 heteroatom(s) selected from N, O, and S, and Ar can be optionally substituted with 1 to 3 same or different R5; R5 is hydroxyl, halogen, nitro, amino, cyano, (C1-C6) alkyl, (C2-C6) alkenyl, (C2-C6) alkynyl, (C1-C6) alkoxyl, (C1-C6) alkyl or (C1-C6) alkoxyl optionally substituted with hydroxyl, amino or halogen, amino substituted with 1 or 2 (C1-C6) alkyl, carboxy group which can be free, salts, or form ester group, (C1-C6) alkylsulfinyl, sulfonyl, (C1-C6) alkoxyl (C1-C6) alkyl, (C1-C6)alkylacyl, aminoformyl, aminoformyl substituted optionally with 1 or 2 (C1-C6) alkyl, or (C1-C3)alkylenedioxo.