Optimization of 3-phenylpyrazolo [1, 5-a] pyrimidines as potent corticotropin-releasing factor-1 antagonists with adequate lipophilicity and water solubility

C Chen, KM Wilcoxen, CQ Huang, JR McCarthy…

Index: Chen, Chen; Wilcoxen, Keith M.; Huang, Charles Q.; McCarthy, James R.; Chen, Takung; Grigoriadis, Dimitri E. Bioorganic and Medicinal Chemistry Letters, 2004 , vol. 14, # 14 p. 3669 - 3673

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Citation Number: 32

Abstract

In our efforts to identify potent CRF1 antagonists with proper physicochemical properties, a series of 3-phenylpyrazolo [1, 5-a] pyrimidines bearing polar groups, such as amino, hydroxyl, methoxy, sulfoxide, were designed and synthesized. Several positions of the core structure were identified, where a polar group was tolerated with slight reduction in receptor binding. NBI 30545 (18n) was found to have good binding affinity and potent antagonistic ...