PYRAZOLOPYRIMIDONE OR PYRROLOTRIAZONE DERIVATIVES, METHOD OF PREPARING SAME, AND PHARMACEUTICAL APPLICATIONS THEREOF

摘要

Pyrazolopyrimidone and pyrrolotriazone derivatives, methods of preparation thereof, and pharmaceutical uses thereof are described. Specifically, pyrazolopyrimidone and pyrrolotriazone derivatives represented by the general formula (I) and pharmaceutically acceptable salts thereof are described. The pyrazolopyrimidone and pyrrolotriazone derivatives are useful as gonadotropin releasing hormone (GnRH) antagonists, such as for therapeutic agents for endometriosis. The definitions of the substituents in the general formula (I) are the same as the definitions in the specification.;

主权项

1. A compound of formula (I), or a tautomer, mesomer, racemate, enantiomer, or diastereomer thereof, or mixture thereof, or a pharmaceutically acceptable salt thereof:wherein:
G is N or C; when G is N, D is C and E is —CH—; when G is C, D and E are N; R1 is selected from the group consisting of alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, and —OR6, wherein the alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl are each independently and optionally further substituted with one or more groups selected from the group consisting of halogen, cyano, nitro, alkyl, haloalkyl, hydroxyalkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, —OR6, —C(O)OR6, —OC(O)R6, —NHS(O)mR6, —C(O)R6, —NHC(O)R6, —NHC(O)OR6, —NR7R8, —OC(O)NR7R8, —C(O)NR7R8, —NHC(O)NHR6, and —NHC(O)NHOR6; R2 is alkyl, wherein the alkyl is further substituted with one or more groups selected from the group consisting of aryl and heteroaryl, wherein the aryl and heteroaryl are each optionally further substituted with one or more groups selected from the group consisting of halogen, alkyl, haloalkyl, cyano, nitro, —C(O)OR6, —C(O)NR7R8, —OC(O)NR7R8, —OR6, —NHS(O)mR6, —NHC(O)R6, and —NR7R8; R3 is selected from the group consisting of aryl and heteroaryl, wherein the aryl and heteroaryl are each optionally further substituted with one or more groups selected from the group consisting of halogen, alkyl, haloalkyl, —OR6, —C(O)OR6, —OC(O)R6, —C(O)R6, —NR7R8, —OC(O)NR7R8, —C(O)NR7R8, —NHS(O)mR6, —NHC(O)R6, —NHC(O)OR6, —NHC(O)NHR6, and —NHC(O)NHOR6; R4 is alkyl; R5 is selected from the group consisting of hydrogen, cycloalkyl, heterocyclyl, aryl, heteroaryl, —OR5, —NR7R8, and —NR7S(O)mR6, wherein the alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl are each optionally further substituted with one or more groups selected from the group consisting of halogen, oxo, alkyl, haloalkyl, hydroxyalkyl, —OR6, —C(O)OR6, —OC(O)R6, —NR7S(O)mR6, —S(O)mR6, —C(O)R6, and —NHC(O)R6; R6 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl, wherein the alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl are each independently and optionally further substituted with one or more groups selected from the group consisting of alkyl, halogen, hydroxy, alkoxy, cycloalkyl, heterocyclyl, aryl, heteroaryl, carboxylic acid, and carboxylic ester; R7 and R8 are each independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl, wherein the alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl are each independently and optionally further substituted with one or more groups selected from the group consisting of alkyl, halogen, hydroxy, alkoxy, cycloalkyl, heterocyclyl, aryl, heteroaryl, carboxylic acid, and carboxylic ester; or, R7 and R8 are taken together with the attached N atom to form a heterocyclyl, wherein the heterocyclyl contains one or more heteroatoms selected from the group consisting of N, O, and S(O)m, and the heterocyclyl is optionally further substituted with one or more groups selected from the group consisting of alkyl, halogen, hydroxyl, alkoxyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, carboxylic acid, and carboxylic ester; m is 0, 1, or 2; n is 1, 2, 3, or 4; and p is 0, 1, or 2.