| Autor: |
Guo, Z., Tellew, J. E., Gross, R. S., Dyck, B., Grey, J., Haddach, M., Kiankarimi, M., Lanier, M., Li, B.-F., Luo, Z., McCarthy, J. R., Moorjani, M., Saunders, J., Sullivan, R., Zhang, X., Zamani-Kord, S., Grigoriadis, D. E., Crowe, P. D., Chen, T. K., Williams, J. P. |
| Zdroj: |
Journal of Medicinal Chemistry; August 2005, Vol. 48 Issue: 16 p5104-5107, 4p |
| Abstrakt: |
The synthesis and SAR studies of tricyclic imidazo[4,5-b]pyridin-2-ones as human corticotropin-releasing factor receptor (CRF1) antagonists are discussed herein. Compound 16g was identified as a functional antagonist that inhibited CRF-stimulated cyclic adenosine monophosphate production and CRF-induced adrenocorticotrophic hormone release. Pharmacokinetics studies in rats showed that 16g was orally bioavailable, had good brain penetration, and had a moderate half-life. In our effort to identify CRF1 antagonists with improved pharmacokinetics properties, 16g exhibited a favorably lower volume of distribution. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
|
