1335195-53-3Relevant academic research and scientific papers
Strategies to lower the Pgp efflux liability in a series of potent indole azetidine MCHR1 antagonists
Lu, Kai,Jiang, Yu,Chen, Bin,Eldemenky, Eman M.,Ma, Gil,Packiarajan, Mathivanan,Chandrasena, Gamini,White, Andrew D.,Jones, Kenneth A.,Li, Boshan,Hong, Sang-Phyo
, p. 5310 - 5314 (2011/10/03)
A series of potent indolyl azetidine rMCHR1 antagonists were found to show poor CNS penetration due to Pgp efflux. We envisioned a strategy which included: lowering basicity; changing the conformational flexibility motif; and removal of a hydrogen bond donor, in an attempt to optimize this property while maintaining target receptor efficacy. This work resulted in mitigation of Pgp efflux, and led us to identify 1-dihydroindolyl azetidine derivatives with CNS penetration and excellent rMCHR1 binding affinity.
