Amide compounds and uses thereof
The present invention relates to novel amide compounds of formula (I), pharmaceutical compositions comprising same, methods for preparing same, and uses thereof, wherein the definition of each symbol is as described in the description.
1. A compound of formula (I):
or a pharmaceutically acceptable salt thereof, and/or a deuterate, a solvate, a racemic mixture, an enantiomer, a diastereomer and a tautomer thereof, wherein
X is N;
Z 1 and Z 2 are both CH;
Y 1 is CR 7 ; Y 2 is N; Y 3 is CR 9 ;
L is O;
W is absent;
R 1 is 5-12 membered heteroaryl, which is optionally substituted with one or more groups chosen from: halogen, C 1-6 alkyl, C 1-6 haloalkyl, —(C 1-6 alkylene) n -NH 2 , —(C 1-6 alkylene) n -NH (C 1-6 alkyl), —(C 1-6 alkylene) n -N(C 1-6 alkyl) 2 , or —(C 1-6 alkylene) n -OH;
R 2 is C 1-6 alkyl;
R 3 , R 4 , and R 7 are each independently chosen from: hydrogen, halogen, C 1-6 alkyl, or —O (C 1-6 alkyl);
R 9 is hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, or C 3-8 cycloalkyl;
n is 0 or 1.
2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, and/or a deuterate, a solvate, a racemic mixture, an enantiomer, a diastereomer and a tautomer thereof, wherein R 7 is hydrogen, C 1-6 alkyl or —O (C 1-6 alkyl); R 9 is hydrogen, C 1-6 alkyl, C 1-6 haloalkyl or C 3-6 cycloalkyl.
3. The compound of claim 2 , or a pharmaceutically acceptable salt thereof, and/or a deuterate, a solvate, a racemic mixture, an enantiomer, a diastereomer and a tautomer thereof, wherein R 7 is hydrogen; R 9 is hydrogen, C 1-6 alkyl or C 3-6 cycloalkyl.
4. The compound of claim 3 , or a pharmaceutically acceptable salt thereof, and/or a deuterate, a solvate, a racemic mixture, an enantiomer, a diastereomer and a tautomer thereof, wherein R 7 is hydrogen; R 9 is hydrogen or methyl.
5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, and/or a deuterate, a solvate, a racemic mixture, an enantiomer, a diastereomer and a tautomer thereof, wherein R 1 is pyrazolyl, pyrrolyl, furanyl, thienyl, pyridyl, thiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, imidazolyl, or imidazo [1,2-a]pyridyl, each of which is optionally substituted with one or more groups chosen from: halogen, C 1-6 alkyl, C 1-6 haloalkyl, —(C 1-6 alkylene) n -NH 2 , —(C 1-6 alkylene) n -NH (C 1-6 alkyl), —(C 1-6 alkylene) n -N(C 1-6 alkyl) 2 or —(C 1-6 alkylene) n -OH.
6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, and/or a deuterate, a solvate, a racemic mixture, an enantiomer, a diastereomer and a tautomer thereof, wherein R 1 is furanyl, thienyl, pyridyl, thiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, imidazolyl, or imidazo [1,2-a]pyridyl, each of which is optionally substituted with one or more C 1-6 alkyl.
7. The compound of claim 1 or a pharmaceutically acceptable salt thereof, and/or a deuterate, a solvate, a racemic mixture, an enantiomer, a diastereomer and a tautomer thereof, wherein R 2 is methyl, ethyl or i-propyl.
8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, and/or a deuterate, a solvate, a racemic mixture, an enantiomer, a diastereomer and a tautomer thereof, wherein R 3 is hydrogen, or halogen; and R 4 is hydrogen.
9. The compound of formula (I) of claim 1 , or a pharmaceutically acceptable salt thereof, which is chosen from:
No.
Structural formula
8
10
13
14
23
30
31
32
33
34
38
39
41
49
56
62
64
66
73
74
109
110
113
116
117
119
120
122
128
129
130
135
10. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, and/or a deuterate, a solvate, a racemic mixture, an enantiomer, a diastereomer and a tautomer thereof, wherein R 1 is pyrazolyl or pyrrolyl, each of which is optionally substituted with one or more groups chosen from: C 1-6 alkyl, C 1-6 haloalkyl, —(C 1-6 alkylene)-NH 2 , —(C 1-6 alkylene)-NH (C 1-6 alkyl), —(C 1-6 alkylene)-N(C 1-6 alkyl) 2 or —(C 1-6 alkylene)-OH.
11. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, and/or a deuterate, a solvate, a racemic mixture, an enantiomer, a diastereomer and a tautomer thereof, wherein R 1 is pyrazolyl or pyrrolyl, each of which is optionally substituted with one or more C 1-6 alkyl.
12. A pharmaceutical composition, comprising the compound of claim 1 , or a pharmaceutically acceptable salt thereof, and optionally comprising a pharmaceutically acceptable excipient.
13. A combination, comprising the compound of claim 1 , or a pharmaceutically acceptable salt thereof, and at least one additional therapeutic agent.
14. The combination of claim 13 wherein the additional therapeutic agent is selected from an anti-neoplastic agent, an immune checkpoint inhibitor or agonist, and a targeted therapeutic agent.
15. The combination of claim 14 , wherein the antineoplastic agent is a chemotherapeutic agent.
16. A method of in vivo or in vitro inhibiting the activity of CSF-1R, comprising contacting CSF-1R with an effective amount of the compound of claim 1 , or a pharmaceutically acceptable salt thereof.
17. A method of treating cancer in a subject, comprising administering to the subject in need thereof an effective amount of the compound of claim 1 , or a pharmaceutically acceptable salt thereof.
18. The method of claim 17 , wherein the cancer is chosen from solid tumor or hematologic malignancy.
19. The method of claim 17 , wherein the cancer is chosen from ovarian cancer, lung cancer, brain tumor, tenosynovial giant cell tumor, gastrointestinal stromal tumor (GIST), gastric cancer, esophageal cancer, colon cancer, colorectal cancer, pancreatic cancer, prostate cancer, breast cancer, cervical cancer, melanoma, mesothelioma, mesothelial carcinoma, renal cancer, liver cancer, thyroid carcinoma, head and neck cancer, urothelial carcinoma, bladder cancer, endometrial cancer, choriocarcinoma, adrenal carcinoma, sarcoma, leukemia, lymphoma or myeloma.
20. The method of claim 17 , wherein the cancer is chosen from non-small cell lung cancer and glioblastoma.