IMIDAZOLINE DERIVATIVES, PREPARATION METHODS THEREOF, AND THEIR APPLICATIONS IN MEDICINE

摘要

New imidazoline derivatives represented by formula (I):;;preparation methods thereof, pharmaceutical compositions comprising such derivatives, and applications of such derivatives in preparing androgen receptor antagonists and medicaments for treating diseases such as prostate cancer are described.

主权项

1. A compound of formula (I), or a tautomer, mesomer, racemate, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof:wherein:
A is —CR′ or N; R′ is hydrogen, halogen, alkyl, cycloalkyl, or heterocyclyl, wherein said alkyl, cycloalkyl, and heterocyclyl are each optionally substituted with one or more groups selected from the group consisting of halogen, cyano, hydroxy, alkyl, alkoxy, carboxyl, and carboxylic ester; Z1 and Z2 are each independently alkyl, or Z1 and Z2 are taken together with the attached carbon atoms to form a cycloalkyl or heterocyclyl; R1 and R2 are each independently selected from the group consisting of S and O; R3 is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, and —S(O)mR6, wherein the alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl are each optionally substituted with one or more groups selected from the group consisting of halogen, cyano, amino, alkyl, haloalkyl, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, —OR6, —C(O)NR7R8, —S(O)mR6, —C(O)R6, —OC(O)R6, —NR7C(O)R8, —NR7C(O)OR8, and —C(O)OR6; wherein the alkyl is substituted with one or more groups selected from the group consisting of halogen, cyano, amino, cycloalkyl, heterocyclyl, aryl, heteroaryl, —OR6, —C(O)NR7R8, —S(O)mR6, —C(O)R6, —OC(O)R6, —NR7C(O)R8, —NR7C(O)OR8, and —C(O)OR6, wherein the cycloalkyl, heterocyclyl, aryl, and heteroaryl are each optionally substituted with one or more groups selected from the group consisting of halogen, cyano, amino, alkyl, haloalkyl, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, —OR6, —C(O)NR7R8, —S(O)mR6, —C(O)R6, —OC(O)R6, —NR7C(O)R8, —NR7C(O)OR8, and —C(O)OR6; R4 and R5 are each independently selected from the group consisting of cyano, nitro, alkyl, haloalkyl, hydroxy, hydrogen, alkoxy, and haloalkoxy; R6 is hydrogen, alkyl, alkenyl, alkynyl, hydroxy, halogen, alkoxy, cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein the alkyl, alkoxy, cycloalkyl, heterocyclyl, aryl and heteroaryl are each optionally substituted with one or more groups selected from the group consisting of halogen, cyano, hydroxy, amino, oxo, alkyl, haloalkyl, hydroxyalkyl, alkoxy, cycloalkyl, heterocyclyl, aryl, heteroaryl, carboxyl, 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 optionally substituted with one or more groups selected from the group consisting of halogen, cyano, hydroxy, amino, oxo, alkyl, haloalkyl, hydroxyalkyl, alkoxy, cycloalkyl, heterocyclyl, aryl, heteroaryl, carboxyl, and carboxylic ester; and m is 0, 1, or 2.