2. Academic Validation
  3. 5-(pyridinon-1-yl)indazoles and 5-(furopyridinon-5-yl)indazoles as MCH-1 antagonists

5-(pyridinon-1-yl)indazoles and 5-(furopyridinon-5-yl)indazoles as MCH-1 antagonists

  • Bioorg Med Chem Lett. 2010 Dec 1;20(23):7015-9. doi: 10.1016/j.bmcl.2010.09.039.
Matthew D Surman 1,  Emily E Freeman,  James F Grabowski,  Mark Hadden,  Alan J Henderson,  Guowei Jiang,  Xiaowu May Jiang,  Michele Luche,  Yuri Khmelnitsky,  Steven Vickers,  Jean Viggers,  Sharon Cheetham,  Peter R Guzzo
Affiliations

Affiliation

  • 1 AMRI, 26 Corporate Circle, Albany, NY 12212-5098, USA. matthew.surman@amriglobal.com
PMID: 20961756 DOI: 10.1016/j.bmcl.2010.09.039
Abstract

A new series of 5-(pyridinon-1-yl)indazoles with MCH-1 antagonist activity were synthesized. Potential cardiovascular risk for these compounds was assessed based upon their interaction with the hERG Potassium Channel in a mini-patch clamp assay. Selected compounds were studied in a 5-day diet-induced obese mouse model to evaluate their potential use as weight loss agents. Structural modification of the 5-(pyridinon-1-yl)indazoles to give 5-(furopyridinon-5-yl)indazoles provided compounds with enhanced pharmacokinetic properties and improved efficacy.

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