US 9,809,604 B2Granted

DGAT1 inhibitor and preparation method and use thereof

AssigneesQingdao Huanghai Pharmaceutical Co., Ltd., Medshine Discovery Inc.

InventorsChengde Wu, Zhiliu Zhang, Tao Yu

Life of this patent

Estimating the term…

Abstract

The present invention discloses a novel DGAT1 inhibitor, especially the compound of formula (I) or a pharmaceutically acceptable salt thereof, preparation and pharmaceutical composition thereof, as well as their uses in the preparation of a medicament for the prevention and treatment of Familial hyperchylomicronemia (FCS), obesity, hyperlipoproteinemia or hypertriglyceridemia.

Claims20

Dependent claims

A compound represented by formula (I)

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
wherein
R6 is selected from the group consisting of
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
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.

10 more elements

A compound selected from the group consisting of:

1) 2-(3-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)-2-chlorophenyl)-2-oxoimidazolidin-1-yl)acetic acid;
2) 2-(3-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)-2-fluorophenyl)-2-oxoimidazolidin-1-yl)acetic acid;
3) 2-(3-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)-2-methylphenyl)-2-oxoimidazolidin-1-yl)acetic acid;
4) 2-(3-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)-2-ethyl-6-methylphenyl)-2-oxoimidazolidin-1-yl)acetic acid;
5) 2-(3-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)-2-ethylphenyl)-2-oxoimidazolidin-1-yl)acetic acid;
6) 3-(3-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)-2-chlorophenyl)-2-oxoimidazolidin-1-yl)propanoic acid;
7) 2-(3-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)-2-(trifluoromethoxy)phenyl)-2-oxoimidazolidin-1-yl)acetic acid;
8) 4-amino-6-(3-chloro-4-(2-oxo-3-(2,2,2-trifluoroethyl)imidazolidin-1-yl)phenyl)-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5(6H)-one;
9) 4-amino-6-(3,5-dimethyl-4-(2-oxo-3-(2,2,2-trifluoroethyl)-2,3-dihydro-1H-benzo[d]imidazol-1-yl)phenyl)-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5(6H)-one;
10) 2-(3-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)phenyl)-2-oxo-2,3-dihydro-1H-imidazol-1-yl)acetic acid;
11) 2-(3-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)phenyl)-2-oxoimidazolidin-1-yl)acetic acid;
12) Ethyl-2-(3-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)phenyl)-2-oxoimidazolidin-1-yl)acetate;
13) 3-(3-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)phenyl)-2-oxoimidazolidin-1-yl)propanoic acid;
14) 2-(3-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)-2-methoxyphenyl)-2-oxoimidazolidin-1-yl)acetic acid;
15) 2-(3-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)phenyl)-2-oxoimidazolidin-1-yl)propanoic acid;
16) 2-(3-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)phenyl)-2-oxo-2,3-dihydro-1H-imidazol-1-yl)acetic acid;
17) 2-(3-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)phenyl)-2-oxoimidazolidin-1-yl)-3-methylbutanoic acid;
18) 2-(3-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)-2,6-dimethylphenyl)-2-oxoimidazolidin-1-yl)acetic acid;
19) 2-(3-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)-2,6-diethylphenyl)-2-oxoimidazolidin-1-yl)acetic acid;
20) 3-(3-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)phenyl)-2-oxo-2,3-dihydro-1H-imidazol-1-yl)propanoic acid;
21) 2-(3-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)-2-(trifluoromethoxy)phenyl)-2-oxo-2,3-dihydro-1H-imidazol-1-yl)acetic acid;
22) 2-(3-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)phenyl)-2-oxo-2,3-dihydro-1H-imidazol-1-yl)propanoic acid;
23) 2-(3-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)phenyl)-2-oxoimidazolidin-1-yl)butanoic acid;
24) 3-(3-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)phenyl)-2-oxoimidazolidin-1-yl)-2-methylpropanoic acid;
25) 2-(3-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)-2-(trifluoromethyl)phenyl)-2-oxoimidazolidin-1-yl)acetic acid;
26) 2-(3-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)-2-fluoro-6-methylphenyl)-2-oxoimidazolidin-1-yl)acetic acid;
27) 2-(3-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)-2-chloro-6-methylphenyl)-2-oxoimidazolidin-1-yl)acetic acid;
28) 2-(3-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)-2-chlorophenyl)-2-oxo-2,3-dihydro-1H-imidazol-1-yl)acetic acid;
29) 4-amino-6-(3-chloro-4-(3-isobutyl-2-oxoimidazolidin-1-yl)phenyl)-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5(6H)-one;
30) 4-amino-6-(3-chloro-4-(3-(cyclopropylmethyl)-2-oxoimidazolidin-1-yl)phenyl)-7, 8-dihydropyrimido[5,4-f][1,4]oxazepin-5(6H)-one;
31) 4-amino-6-(3-chloro-4-(3-(2-fluoro-2-methylpropyl)-2-oxoimidazolidin-1-yl)phenyl)-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5(6H)-one;
32) 2-(4-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)phenyl)-3,5-dimethyl-1H-pyrazol-1-yl)acetic acid;
33) 2-(4-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)-2-chlorophenyl)-1H-pyrazol-1-yl)-2-methylpropanoic acid;
34) 2-(4-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)-2-chlorophenyl)-1H-pyrazol-1-yl)propanoic acid;
35) 3-(4-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)-2-chlorophenyl)-1H-pyrazol-1-yl)propanoic acid;
36) 2-(4-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)-2-chlorophenyl)-3-methyl-1H-pyrazol-1-yl)acetic acid;
37) 3-(4-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)-2-fluorophenyl)-1H-pyrazol-1-yl)propanoic acid;
38) 3-(4-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)-2-chlorophenyl)-3,5-dimethyl-1H-pyrazol-1-yl)propanoic acid;
39) 2-(4-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)phenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetic acid;
40) 4-amino-6-(3-chloro-4-(3-methyl-1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)phenyl)-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5(6H)-one;
41) 4-amino-6-(3,5-dimethyl-4-(3-methyl-1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)phenyl)-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5(6H)-one;
42) 4-amino-6-(3-chloro-4-(1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl)phenyl)-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5(6H)-one;
43) 4-amino-6-(4-(1-(2,2-difluoroethyl)-3-methyl-1H-pyrazol-4-yl)-3,5-dimethylphenyl)-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5(6H)-one;
44) 4-amino-6-(3-chloro-4-(1-(3-hydroxy-2,2-dimethylpropyl)-1H-pyrazol-4-yl)phenyl)-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5(6H)-one;
45) (R)-4-amino-6-(3-chloro-4-(1-isobutyl-1H-pyrazol-4-yl)phenyl)-8-methyl-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5(6H)-one;
46) 2-(4-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)-2-chlorophenyl)-1H-pyrazol-1-yl)acetamide;
47) 4-amino-6-(3,5-dimethyl-4-(3-methyl-1-((3-methyloxetan-3-yl)methyl)-1H-pyrazol-4-yl)phenyl)-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5(6H)-one;
48) 4-amino-6-(4-(1-(2,2-difluoropropyl)-3-methyl-1H-pyrazol-4-yl)-3,5-dimethylphenyl)-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5(6H)-one;
49) 2-(4-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)phenyl)-1H-pyrazol-1-yl)acetic acid;
50) 3-(4-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)phenyl)-1H-pyrazol-1-yl)propanoic acid;
51) 2-(4-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)phenyl)-1H-pyrazol-1-yl)propanoic acid;
52) 2-(4-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)phenyl)-1H-pyrazol-1-yl)butanoic acid;
53) 2-(4-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)phenyl)-1H-pyrazol-1-yl)-3-methylbutanoic acid;
54) 2-(4-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)phenyl)-1H-pyrazol-1-yl)-2-methylpropanoic acid;
55) 2-(4-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)phenyl)-3-methyl-1H-pyrazol-1-yl)acetic acid;
56) 2-(4-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)-2-chlorophenyl)-1H-pyrazol-1-yl)acetic acid;
57) 2-(4-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)-2-methylphenyl)-1H-pyrazol-1-yl)acetic acid;
58) 2-(4-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)-2-methylphenyl)-1H-pyrazol-1-yl)propanoic acid;
59) 2-(4-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)-2-methylphenyl)-1H-pyrazol-1-yl)-3-methylbutanoic acid;
60) 3-(4-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)-2-methylphenyl)-1H-pyrazol-1-yl)propanoic acid;
61) 2-(4-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)-2-chlorophenyl)-1H-pyrazol-1-yl)butanoic acid;
62) 3-(4-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)phenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)propanoic acid;
63) 2-(4-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)-2-methylphenyl)-1H-pyrazol-1-yl)-2-methylpropanoic acid;
64) 2-(4-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)-2-methylphenyl)-1H-pyrazol-1-yl)butanoic acid;
65) 2-(4-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)-2-chlorophenyl)-1H-pyrazol-1-yl)-3-methylbutanoic acid;
66) 2-(4-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)-2,6-dimethylphenyl)-1H-pyrazol-1-yl)-2-methylpropanoic acid;
67) 2-(4-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)-2,6-dimethylphenyl)-1H-pyrazol-1-yl)acetic acid;
68) 4-amino-6-(3-chloro-4-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)phenyl)-7, 8-dihydropyrimido[5,4-f][1,4]oxazepin-5(6H)-one;
69) 2-(4-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)-2-methoxyphenyl)-1H-pyrazol-1-yl)acetic acid;
70) 3-(4-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)-2,6-dimethylphenyl)-1H-pyrazol-1-yl)propanoic acid;
71) 3-(4-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)-2-chlorophenyl)-1H-pyrazol-1-yl)-2,2-dimethylpropanoic acid;
72) 2-(4-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)-2-chlorophenyl)-3,5-dimethyl-1H-pyrazol-1-yl)acetic acid;
73) 2-(4-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)-2,6-dimethylphenyl)-3-methyl-1H-pyrazol-1-yl)acetic acid;
74) 3-(4-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)-2-methoxyphenyl)-1H-pyrazol-1-yl)propanoic acid;
75) 2-(4-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)-2-fluorophenyl)-1H-pyrazol-1-yl)acetic acid;
76) 3-(4-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)phenyl)-3,5-dimethyl-1H-pyrazol-1-yl)propanoic acid;
77) 3-(4-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)-2-methylphenyl)-3,5-dimethyl-1H-pyrazol-1-yl)propanoic acid;
78) 3-(4-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)-2-chlorophenyl)-3-methyl-1H-pyrazol-1-yl)propanoic acid;
79) 4-amino-6-(3-chloro-4-(1-ethyl-1H-pyrazol-4-yl)phenyl)-7, 8-dihydropyrimido[5,4-f][1,4]oxazepin-5(6H)-one;
80) 4-amino-6-(3-chloro-4-(1-isobutyl-1H-pyrazol-4-yl)phenyl)-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5(6H)-one;
81) 4-amino-6-(3-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)phenyl)-7, 8-dihydropyrimido[5,4-f][1,4]oxazepin-5(6H)-one;
82) 4-amino-6-(3-chloro-4-(1-(2-hydroxyethyl)-1H-pyrazol-4-yl)phenyl)-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5(6H)-one;
83) 3-(4-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)-2,6-dimethylphenyl)-3-methyl-1H-pyrazol-1-yl)propanoic acid;
84) 2-(4-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)-2-chlorophenyl)-1H-pyrazol-1-yl)acetonitrile;
85) 4-amino-6-(3-chloro-4-(1-(2,2-dimethyl-3-oxo-3-(pyrrolidin-1-yl)propyl)-1H-pyrazol-4-yl)phenyl)-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5(6H)-one;
86) 4-amino-6-(3-chloro-4-(1-isobutyl-1H-pyrazol-4-yl)phenyl)-8,8-dimethyl-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5(6H)-one;
87) 4-amino-6-(3-chloro-4-(1-(cyclopropylmethyl)-1H-pyrazol-4-yl)phenyl)-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5(6H)-one;
88) 4-amino-6-(3-chloro-4-(1-neopentyl-1H-pyrazol-4-yl)phenyl)-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5(6H)-one;
89) 3-(4-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)-2-chlorophenyl)-1H-pyrazol-1-yl)-N,N,2,2-tetramethylpropanamide;
90) 4-amino-6-(3-ethyl-4-(1-isobutyl-1H-pyrazol-4-yl)phenyl)-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5(6H)-one;
91) 4-amino-6-(3-chloro-4-(1-(2-fluoro-2-methylpropyl)-1H-pyrazol-4-yl)phenyl)-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5(6H)-one;
92) 4-amino-6-(3-chloro-4-(1-isobutyl-1H-pyrazol-4-yl)phenyl)-7,7-dimethyl-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5(6H)-one;
93) 4-amino-6-(4-(3,5-dimethyl-1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)-3,5-dimethylphenyl)-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5(6H)-one;
94) 4-amino-6-(3-chloro-4-(1-(2-methoxy-2-methylpropyl)-1H-pyrazol-4-yl)phenyl)-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5(6H)-one;
95) 4-amino-6-(3-chloro-4-(1-(2-fluoro-2-methylpropyl)-1H-pyrazol-3-yl)phenyl)-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5(6H)-one;
96) (R)-4-amino-6-(3-chloro-4-(1-isobutyl-1H-pyrazol-4-yl)phenyl)-7-methyl-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5(6H)-one;
97) 4-amino-6-(4-(1-(2-fluoro-2-methylpropyl)-3-methyl-1H-pyrazol-4-yl)-3,5-dimethylphenyl)-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5(6H)-one;
98) 4-amino-6-(4-(1-(2-hydroxy-2-methylpropyl)-3-methyl-1H-pyrazol-4-yl)-3,5-dimethylphenyl)-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5(6H)-one;
99) 4-amino-6-(4-(1-(2-methoxy-2-methylpropyl)-3-methyl-1H-pyrazol-4-yl)-3,5-dimethylphenyl)-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5(6H)-one;
100) 4-amino-6-(4-(2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridin-3-yl)phenyl)-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5(6H)-one;
101) 4-amino-6-(3,5-dimethyl-4-(6-oxo-1-(2,2,2-trifluoroethyl)-1,6-dihydropyridin-3-yl)phenyl)-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5(6H)-one;
102) 4-amino-6-(3-chloro-4-(1-(2-fluoro-2-methylpropyl)-1H-imidazol-4-yl)phenyl)-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5(6H)-one;
105) 4-amino-6-(3,5-dimethyl-4-(1-oxo-2-(2,2,2-trifluoroethyl)-1,2-dihydroisoquinolin-7-yl)phenyl)-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5(6H)-one;
106) (E)-4-amino-6-(6-((2,2,2-trifluoroethoxy)imino)-5,6,7,8-tetrahydronaphthalen-2-yl)-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5(6H)-one;
107) (Z)-4-amino-6-(5-((2,2,2-trifluoroethoxy)imino)-5,6,7,8-tetrahydronaphthalen-2-yl)-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5(6H)-one;
108) 4-amino-6-(6-(2,2,2-trifluoroethoxy)-5,6,7,8-tetrahydronaphthalen-2-yl)-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5(6H)-one;
and
109) 4-amino-6-(3,5-dimethyl-4-(3-methyl-2-(2,2,2-trifluoroethyl)-2H-indazol-5-yl)phenyl)-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5(6H)-one.

105 more elements

A method for preparing a compound represented by formula (I)

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
wherein
R6 is selected from the group consisting of
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
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, comprising the following step,
wherein
Y is selected from the group consisting of CF3, halogen, OH, SH, NH2, PH2, and C1-6 alkyl, wherein the C1-6 alkyl is optionally substituted by one or more substituents selected from the group consisting of halogen, OH, SH, NH2, and PH2.

12 more elements

Dependencies are inferred from the claim text.

Facts

Application: 14/912,428Filed 18 Aug 2014
Priority: CN 2013 1 037106923 Aug 2013
Published: US 2016/0272651 A122 Sep 2016
Granted: 7 Nov 2017
Term ends: Not estimatedThe source records don’t support an estimate.

Classification8 codes

C07D 498/04
In which the condensed system contains two hetero rings: ortho-condensed systems
A61K 31/553
Having seven-membered rings, e.g. azelastine, pentylenetetrazole: having at least one nitrogen and one oxygen as ring hetero atoms, e.g. loxapine,…
A61P 3/04
Drugs for disorders of the metabolism: anorexiants; Antiobesity agents
A61P 3/06
Drugs for disorders of the metabolism: antihyperlipidemics

Family

US 2016/0272651 A1Pre-grant publication · published 22 Sep 2016
US 9,809,604 B2This patent

From the US filing history. Foreign family members aren’t listed.

Timeline

Citations

Open elsewhere

patentgrep

Loading patent…

Abstract

A compound represented by formula (I)

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
wherein
R6 is selected from the group consisting of
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
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.

10 more elements

Facts

Application

14/912,428Filed 18 Aug 2014

Priority

CN 2013 1 037106923 Aug 2013

Published

US 2016/0272651 A122 Sep 2016

Granted

7 Nov 2017

Term ends

Not estimatedThe source records don’t support an estimate.

Classification8 codes

C07D 498/04
In which the condensed system contains two hetero rings: ortho-condensed systems
A61K 31/553
Having seven-membered rings, e.g. azelastine, pentylenetetrazole: having at least one nitrogen and one oxygen as ring hetero atoms, e.g. loxapine,…
A61P 3/04
Drugs for disorders of the metabolism: anorexiants; Antiobesity agents
A61P 3/06
Drugs for disorders of the metabolism: antihyperlipidemics