- Discovery of NBI-77860/GSK561679, a potent corticotropin-releasing factor (CRF1) receptor antagonist with improved pharmacokinetic properties
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Antagonists of the corticotropin-releasing factor (CRF) neuropeptide may prove effective in treating stress and anxiety related disorders. In an effort to identify antagonists with improved physico-chemical properties a new series of CRF1 antagonists were designed to substitute the propyl groups at the C7 position of the pyrazolo[1,5-a]pyrimidine core of 1 with heterocycles. Compound (S)-8d was identified as a high affinity ligand with a pKi value of 8.2 and a functional CRF1 antagonist with pIC50 value of 7.0 in the in vitro CRF ACTH production assay.
- Tellew, John E.,Lanier, Marion,Moorjani, Manisha,Lin, Emily,Luo, Zhiyong,Slee, Deborah H.,Zhang, Xiaohu,Hoare, Sam R.J.,Grigoriadis, Dimitri E.,Denis, Yves St.,Fabio, Romano Di,Modugno, Enza Di,Saunders, John,Williams, John P.
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scheme or table
p. 7259 - 7264
(2011/02/22)
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- PYRAZOLO [1,5-ALPHA] PYRIMIDINYL DERIVATIVES USEFUL AS CORTICOTROPIN-RELEASING FACTOR (CRF) RECEPTOR ANTAGONISTS
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CRF receptor antagonists are disclosed which may have utility in the treatment of a variety of disorders, including the treatment of disorders manifesting hypersecretion of CRF in mammals. The CRF receptor antagonists of this invention have the following structure: (I); and pharmaceutically acceptable salts, esters, solvates, stereoisomers and prodrugs thereof, wherein R1, R2a, R2b, Y, Het, n, o, R6, Ar and R7 are as defined herein. Compositions containing a CRF receptor antagonist in combination with a pharmaceutically acceptable carrier are also disclosed, as well as methods for use of the same.
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Page/Page column 83
(2008/06/13)
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