Imidazoline derivatives, preparation methods thereof, and their applications in medicine
AssigneesShanghai Hengrui Pharmaceutical Co., Ltd., Jiangsu Hengrui Medicine Co., Ltd.
InventorsHejun Lu, Piaoyang Sun, Hongbo Fei, Hongjian Jiang, Haowei Wang, Qing Dong
Life of this patent
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Abstract
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.
Claims21
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′;
- R′ is hydrogen, halogen, or alkyl;
- Z1 and Z2 are each independently alkyl;
- R1 is S and R2 is O;
- R3 is alkyl
- substituted with one or more groups selected from the group consisting of halogen, cyano, amino, C3-6cycloalkyl, heterocyclyl, —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 C3-6, cycloalkyl and heterocyclyl are each optionally substituted with one or more groups selected from the group consisting of halogen, cyano, amino, alkyl, haloalkyl, hydroxyalkyl, —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, halogen, or alkoxy wherein the alkyl and alkoxy are each optionally substituted with one or more groups selected from the group consisting of halogen, cyano, hydroxy, amino, oxo, alkyl, haloalkyl, hydroxyalkyl, and alkoxy;
- R7 and R8 are each independently selected from the group consisting of hydrogen and alkyl, wherein the alkyl is optionally substituted with one or more groups selected from the group consisting of halogen, cyano, hydroxy, amino, oxo, alkyl, haloalkyl, hydroxyalkyl, and alkoxy;
- and
- the heterocyclyl is a 3 to 6-membered ring having 1 to 2 oxygen atoms;
- and
- m is 0, 1, or 2.
A compound of formula (I), or a tautomer, mesomer, racemate, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from the group consisting of:
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′;
- R′ is hydrogen or halogen;
- Z1 and Z2 are each independently alkyl;
- R1 is S;
- R2 is O;
- R3 is an alkyl group substituted with one or more groups selected from the group consisting of halogen, hydroxy, amino, cyano, —C(O)NR7R8, —S(O)mR6, —C(O)R6, —C(O)OR6, —NR7C(O)OR8, and C3-6 cycloalkyl, wherein the C3-6 cycloalkyl is optionally substituted with one or more groups selected from the group consisting of amino, hydroxy, alkyl, cyano, —C(O)NR7R8, —NR7C(O)OR8, and —C(O)OR6;
- R4 and R5 are each independently selected from the group consisting of cyano, alkyl, haloalkyl, and hydrogen;
- R6, R7, and R8 are each independently selected from the group consisting of hydrogen and alkyl;
- and
- m is 2.
Dependencies are inferred from the claim text.