Phthalazinone ketone derivative, preparation method thereof, and pharmaceutical use thereof

摘要

A phthalazinone ketone derivative as represented by formula (I), a preparation method thereof, a pharmaceutical composition containing the derivative, a use thereof as a poly (ADP-ribose) polymerase (PARP) inhibitor, and a cancer treatment method thereof are described.;

主权项

1. A compound of formula (I) or a pharmaceutically acceptable salt thereof:wherein:
A and B are taken together with the attached carbon atoms to form an aryl or heteroaryl, wherein said aryl or heteroaryl is each independently and optionally substituted with one or more groups selected from the group consisting of an alkyl, halogen, hydroxyl, alkoxyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, —C(O)OR5, —OC(O)R5, —O(CH2)nC(O)OR5, —C(O)R5, —NHC(O)R5, —NR6R7, —OC(O)NR6R7 and —C(O)NR6R7; R1, R2, R3 or R4 is each independently selected from the group consisting of hydrogen, a halogen, alkyl, cyano and alkoxyl, wherein said alkyl or alkoxyl is each independently and optionally substituted with one or more groups selected from the group consisting of a halogen, hydroxyl, alkyl and alkoxyl; D, E, or G is each independently selected from the group consisting of nitrogen atom and C(R8); R5 is selected from the group consisting of hydrogen, an alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl, wherein said alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl is each independently and optionally substituted with one or more groups selected from the group consisting of an alkyl, halogen, hydroxyl, alkoxyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, carboxyl and alkoxycarbonyl; R6 or R7 is each independently selected from the group consisting of hydrogen, an alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl, wherein said alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl is each independently and optionally substituted with one or more groups selected from the group consisting of an alkyl, halogen, hydroxyl, alkoxyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, carboxyl and alkoxycarbonyl; alternatively, R6 and R7 are taken together with the attached N atom to form a heterocyclyl, wherein said heterocyclyl contains one or more N, O or S(O)m heteroatoms, and said heterocyclyl is optionally substituted with one or more groups selected from the group consisting of an alkyl, halogen, hydroxyl alkoxyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, carboxyl and alkoxycarbonyl; R8 is selected from the group consisting of hydrogen, an alkyl, halogen, hydroxyl, cyano, alkoxyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, benzyl, —C(O)OR5, —OC(O)R5, —O(CH2)nC(O)OR5, —(CH2)nNR6R7, —C(O)R5, —NHC(O)R5, —NR6R7, —OC(O)NR6R7 and —C(O)NR6R7, wherein said alkyl, alkoxyl, cycloalkyl, heterocyclyl, aryl, heteroaryl or benzyl is each independently and optionally substituted with one or more groups selected from the group consisting of an alkyl, halogen, hydroxyl, alkoxyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, oxo, —C(O)OR5, —OC(O)R5, —O(CH2)nC(O)OR5, —C(O)R5, —NHC(O)R5, —NR6R7, —OC(O)NR6R7 and —C(O)NR6R7; m is selected from the group consisting of 0, 1 and 2; and n is selected from the group consisting of 0, 1 and 2.