Synthesis and SAR of 8-Arylquinolines as potent corticotropin-Releasing factor 1 (CRF 1) receptor antagonists

…, TR Webb, J Gu, YF Xie, DE Grigoriadis, C Chen

Index: Huang, Charles Q.; Wilcoxen, Keith; McCarthy, James R.; Haddach, Mustapha; Webb, Thomas R.; Gu, Jian; Xie, Yun-Feng; Grigoriadis, Dimitri E.; Chen, Chen Bioorganic and Medicinal Chemistry Letters, 2003 , vol. 13, # 19 p. 3375 - 3379

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Citation Number: 19

Abstract

A series of 4-substituted 8-aryl-2-methylquinolines 4 was designed and synthesized as highly potent antagonists for the human CRF1 receptor. This series of compounds displayed parallel SAR to other bicyclic systems such as pyrazolo [1, 5-a] pyrimidines, with several compounds possessing low nanomolar binding affinity. In addition to the high potency, the basicity of this 4-aminoquinoline core may offer CRF1 antagonists with lower lipophilicity.