| 摘要 |
The present invention is directed to imidazolin-5-one derivatives, pharmaceutical compositions containing them, and their use as FASN inhibitors, in for example, the treatment of cancer, obesity related disorders, and liver related disorders. Such compounds are represented by formula (I) as follows:;wherein R1, R2, R3, R4, R5, m, n, and;;are defined herein. |
| 主权项 |
1. A compound of formula (I) wherein R1 is C1-4alkyl and fluorinated C1-2alkyl; R2 is selected from the group consisting of C1-4alkyl, fluorinated C1-2alkyl, —(C1-4 alkyl)-O—(C1-4alkyl), C3-6cycloalkyl, phenyl and 5 to 6 membered heteroaryl; wherein the phenyl or 5 to 6 membered heteroaryl is optionally substituted with one to two substituents independently selected from the group consisting of halogen, C1-4alkyl, fluorinated C1-2alkyl, C1-4alkoxy, fluorinated C1-2alkoxy and cyano; m is an integer from 0 to 1; and n is an integer from 0 to 1; provided that each of m and n are not 1;is selected from the group consisting of azetidin-3-yl, pyrrolidin-3-yl and piperidin-4-yl;
R3 is selected from the group consisting of C1-4alkyl, fluorinated C1-4alkyl, C2-4alkenyl, C3-6cycloalkyl, —(C1-4alkyl)-(C3-6cycloalkyl), 4 to 6 membered, saturated heterocyclyl, —(C1-4alkyl)-(4 to 6 membered, saturated heterocyclyl), 5 to 6 membered heteroaryl and —(C1-4alkyl)-(5 to 6 membered heteroaryl);wherein the C3-6cycloalkyl, 4 to 6 membered, saturated heterocyclyl or 5 to 6 membered heteroaryl, whether alone or as part of a substituent group, is optionally substituted with one to two substituents independently selected from the group consisting of halogen, hydroxy, cyano, C1-4alkyl, fluorinated C1-4alkyl, C1-4alkoxy, fluorinated C1-4alkoxy and NRARB; wherein RA and RB are each independently selected from the group consisting of hydrogen and C1-4alkyl;
a is an integer from 0 to 2; each R4 is independently selected from the group consisting of hydroxy, halogen, C1-4alkyl, fluorinated C1-4alkyl, C1-4alkoxy, fluorinated C1-4alkoxy, cyano, and NRCRD; wherein RD and RD are each independently selected from the group consisting of hydrogen and C1-4alkyl; R5 is selected from the group consisting of aryl and heteroaryl; wherein the aryl or heteroaryl is optionally substituted with one to two substituents independently selected from the group consisting of hydroxy, halogen, cyano, nitro, C1-4alkyl, fluorinated C1-4alkyl, hydroxy substituted C1-4alkyl, C1-4alkoxy, fluorinated C1-4alkoxy, NRERF, —(C1-4alkyl)-NRERF, —C(O)—(C1-4alkyl), —C(O)—NRERF, —C(O)OH, —C(O)O—(C1-4alkyl), —NRE—C(O)—(C1-4alkyl) and —NRE—SO2—(C1-4alkyl); wherein RE and RF are each independently selected from the group consisting of hydrogen and C1-4alkyl; alternatively, R5 iswherein R6 is selected from the group consisting of phenyl and 5 to 6 membered heteroaryl; wherein the phenyl or 5 to 6 membered heteroaryl is optionally substituted with with one to two substituents independently selected from the group consisting of hydroxy, halogen, cyano, nitro, C1-4alkyl, fluorinated C1-4alkyl, hydroxy substituted C1-4alkyl, C1-4alkoxy, fluorinated C1-4alkoxy, NRGRH, —C(O)—NRR″, —C(O)OH, —C(O)O—(C1-4alkyl) and —(C1-4alkyl)-NRGRH; wherein RG and RH are each independently selected from the group consisting of hydrogen and C1-4alkyl;
or a stereoisomer, tautomer or pharmaceutically acceptable salt thereof. |
