| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1371175 | Bioorganic & Medicinal Chemistry Letters | 2011 | 8 Pages |
Abstract
We discovered novel pyrrolidine MCHR1 antagonist 1 possessing moderate potency. Profiling of pyrrolidine 1 demonstrated that it was an inhibitor of the hERG channel. Investigation of the structure–activity relationship of this class of pyrrolidines allowed us to optimize the MCHR1 potency and decrease the hERG inhibition. Increasing the acidity of the amide proton by converting the benzamide in lead 1 to an anilide provided single digit nanomolar MCHR1 antagonists while replacing the dimethoxyphenyl ring of 1 with alkyl groups possessing increased polarity dramatically reduced the hERG inhibition.
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Related Topics
Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Brian M. Fox, Reina Natero, Kevin Richard, Richard Connors, Philip M. Roveto, Holger Beckmann, Katrin Haller, Justin Golde, Shou-Hua Xiao, Frank Kayser,