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Discovery of MK-4409, a Novel Oxazole FAAH Inhibitor for the Treatment of Inflammatory and Neuropathic Pain

Authors :
Catherine Abbadie
Raul F. Alvaro
Lin-Lin Shiao
Mark Rosenbach
Lisa F. Frey
Marc D. Chioda
Ravi P. Nargund
Richard Hajdu
Kathleen Sullivan
Robert J. DeVita
Joseph F. Leone
Kevin M. Belyk
Jenna L. Terebetski
Amanda K. Makarewicz
Elliot J. Martel
Gino Salituro
Bindhu V. Karanam
Raman K. Bakshi
James Dellureficio
Selena Fung
Ping Liu
Linda Chang
Nina Jochnowitz
Shruti Mistry
Joyce Shuman
Linus S. Lin
Yan Guo
Maria Madeira
Shane W. Krska
Mark McLaughlin
Erin McGowan
Harry R. Chobanian
Jessica Alexander
Matthew J. Wyvratt
Qingmei Hong
Thomas J. Lanza
Source :
ACS Medicinal Chemistry Letters. 5:717-721
Publication Year :
2014
Publisher :
American Chemical Society (ACS), 2014.

Abstract

We report herein the identification of MK-4409, a potent and selective fatty acid amide hydrolase (FAAH) inhibitor. Starting from a high throughput screening (HTS) hit, medicinal chemistry efforts focused on optimizing of FAAH inhibition in vitro potency, improving the pharmacokinetic (PK) profile, and increasing in vivo efficacy in rodent inflammatory and neuropathic pain assays.

Details

ISSN :
19485875
Volume :
5
Database :
OpenAIRE
Journal :
ACS Medicinal Chemistry Letters
Accession number :
edsair.doi.dedup.....0dbc5aefed73bfbd91d72c5b2ca7e347
Full Text :
https://doi.org/10.1021/ml5001239