US 9,809,604 B2
DGAT1 inhibitor and preparation method and use thereof
Chengde Wu, Shanghai (CN); Zhiliu Zhang, Shanghai (CN); and Tao Yu, Shanghai (CN)
Assigned to Qingdao Huanghai Pharmaceutical Co., Ltd., Qingdao (CN); and Medshine Discovery Inc., Nanjing, Jiangsu (CN)
Appl. No. 14/912,428
Filed by Qingdao Huanghai Pharmaceutical Co., Ltd., Qingdao (CN); and Medshine Discovery Inc., Nanjing, Jiangsu (CN)
PCT Filed Aug. 18, 2014, PCT No. PCT/CN2014/084586
§ 371(c)(1), (2) Date Feb. 17, 2016,
PCT Pub. No. WO2015/024486, PCT Pub. Date Feb. 26, 2015.
Claims priority of application No. 2013 1 0371069 (CN), filed on Aug. 23, 2013.
Prior Publication US 2016/0272651 A1, Sep. 22, 2016
Int. Cl. C07D 498/04 (2006.01); A61K 31/553 (2006.01); A61P 3/10 (2006.01); A61P 3/04 (2006.01)
CPC C07D 498/04 (2013.01) [A61K 31/553 (2013.01)] 20 Claims
 
1. A compound represented by formula (I)

OG Complex Work Unit Drawing
wherein
R1a, R1b, R2, R3a, R3b, R4a, and R4b are each independently selected from the group consisting of H, C1-10 alkyl, C1-10 alkoxy, C3-10 cycloalkyl, and C3-10 cycloalkoxy, wherein each of the C1-10 alkyl, C1-10 alkoxy, C3-10 cycloalkyl, or C3-10 cycloalkoxy is optionally substituted by one or more substituents, each independently selected from the group consisting of halogen, OH, SH, NH2, and PH2,
R5 is

OG Complex Work Unit Drawing
 wherein
R6 is selected from the group consisting of

OG Complex Work Unit Drawing
and R6 is optionally protected by a protecting group, wherein
R14 and R15 are each independently selected from the group consisting of H, C1-6 alkyl, and C1-6 alkoxy, wherein each of the C1-6 alkyl or C1-6 alkoxy is optionally substituted by one to three substituents, each independently selected from the group consisting of halogen, OH, SH, NH2, and PH2; and
R16, R17, R18, R19, R20, R22, R23, R25, R26, R27, R28, R29, R30, R31, R32, R33, R34, R35, R36, R38, R39, and R40 are each independently selected from the group consisting of H, halogen, OH, SH, NH2, PH2, C1-6 alkyl, C1-6 alkoxy, —C1-6OH, —COOH, —C1-6COOH, —OC1-6COOH, —C1-6OC1-6, —C1-6COOC1-6, —C1-6CN, —C1-6CONH2, and

OG Complex Work Unit Drawing
 wherein said C1-6 alkyl, C1-6 alkoxy, —C1-6OH, —C1-6COOH, —OC1-6COOH, —C1-6OC1-6, —C1-6COOC1-6, —C1-6CN, and —C1-6CONH2 are optionally substituted by one to three substituents, each independently selected from the group consisting of halogen, OH, SH, NH2, PH2, and C1-6 cycloalkyl, the carbon atoms, located on both sides or on the same side of each oxygen or carbonyl in said —C1-6OC1-6 or —C1-6COOC1-6, are optionally joined together to form a ring, and the H atom, connected with the N atom of —C1-6NH2, is optionally replaced by C1-6 alkyl singly or bothly;
R7, R8, R9, and R10 are each independently selected from the group consisting of C1-10 alkyl, C1-10 alkoxy, C3-10 cycloalkyl, C3-10 cycloalkoxy, H, halogen, OH, SH, NH2, PH2, and CN, wherein each of the C1-10 alkyl, C1-10 alkoxy, C3-10 cycloalkyl, and C3-10 cycloalkoxy is optionally substituted by one or more substituents, each independently selected from the group consisting of halogen, OH, SH, NH2, PH2, CN, CH3, and CF3;
R11, R12, and R13 are each independently selected from the group consisting of C1-10 alkyl, C1-10 alkoxy, C3-10 cycloalkyl, and C3-10 cycloalkoxy, wherein each of the C1-10 alkyl, C1-10 alkoxy, C3-10 cycloalkyl, and C3-10 cycloalkoxy is optionally substituted by one to three substituents, each independently selected from the group consisting of halogen, OH, SH, NH2, PH2, CN, CF3, —OCF3, and —OCH3,
or a pharmaceutically acceptable salt thereof.
 
17. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 1 and a pharmaceutical acceptable carrier.