Thiazole pyrazolopyrimidines CRF1 receptor antagonists
The present invention relates to compounds of Formula (I), pharmaceutical compositions thereof, and use thereof as corticotropin releasing factor 1 (CRF1) receptor antagonists in the treatment of psychiatric and neuroendocrine disorders, neurological diseases, and metabolic syndrome.
1. A compound of Formula I
wherein:
R 1 and R 2 are independently ethyl or n-propyl;
R 3 is hydrogen, Cl, Br, methyl, trifluoromethyl or methoxy;
R 4 is hydrogen, Br, R a R b N—, methoxymethyl, n-butyl, acetamido, pyridin-4-yl, morpholin-4-yl,
R a and R b are independently hydrogen, C 1 -C 3 alkyl, H 2 NCH 2 CH 2 —, (CH 3 ) 3 COC(O)NHCH 2 CH 2 —, or CH 3 CH 2 CH 2 NHCH 2 CH 2 —;
or a pharmaceutically acceptable salt thereof.
2. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 3 is Cl, Br, methyl or trifluoromethyl.
3. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 3 is Cl or Br.
4. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4 is R a R b N—, pyridin-4-yl, morpholin-4-yl, or
5. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4 is morpholin-4-yl or
6. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4 is R a R b N— and R a and R b are independently C 1 -C 3 alkyl.
7. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, which is 3-[4-bromo-2-(2-methyl-2H-[1,2,4]triazol-3-yl)-thiazol-5-yl]-2,5-dimethyl-7-(1-propyl-butyl)-pyrazolo[1,5-a]pyrimidine.
8. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, which is 3-(4-bromo-2-(2-methyl-2H-[1,2,4]triazol-3-yl)-thiazol-5-yl)-7-(1-ethyl-propyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidine.
9. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, which is 3-(4-chloro-2-morpholin-4-yl-thiazol-5-yl)-7-(1-ethyl-propyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidine.
10. A pharmaceutical composition comprising: a compound according to claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.