Journal article
Identification of a Nonbasic Melanin Hormone Receptor 1 Antagonist as an Antiobesity Clinical Candidate
Journal of medicinal chemistry, v 57(18), pp 7509-7522
25 Sep 2014
PMID: 25165888
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Identification of MCHR1 antagonists with a preclinical safety profile to support clinical evaluation as antiobesity agents has been a challenge. Our finding that a basic moiety is not required for MCHR1 antagonists to achieve high affinity allowed us to explore structures less prone to off-target activities such as hERG inhibition. We report the SAR evolution of hydroxylated thienopyrimidinone ethers culminating in the identification of 27 (BMS-819881), which entered obesity clinical trials as the phosphate ester prodrug 35 (BMS-830216).
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Details
- Title
- Identification of a Nonbasic Melanin Hormone Receptor 1 Antagonist as an Antiobesity Clinical Candidate
- Creators
- William N. Washburn - Bristol-Myers SquibbMark Manfredi - Bristol-Myers SquibbPratik Devasthale - Bristol-Myers SquibbGuohua Zhao - Bristol-Myers SquibbSaleem Ahmad - Bristol-Myers SquibbAndres Hernandez - Bristol-Myers SquibbJeffrey A. Robl - Bristol-Myers SquibbWei Wang - Bristol-Myers SquibbJames Mignone - Bristol-Myers SquibbZhenghua Wang - Bristol-Myers SquibbKhehyong Ngu - Bristol-Myers SquibbMary Ann Pelleymounter - Bristol-Myers SquibbDaniel Longhi - Bristol-Myers SquibbRulin Zhao - Bristol-Myers SquibbBei Wang - Bristol-Myers SquibbNing Huang - Bristol-Myers SquibbNeil Flynn - Bristol-Myers SquibbAnthony V. Azzara - Bristol-Myers SquibbJoel C. Barrish - Bristol-Myers SquibbKenneth Rohrbach - Bristol-Myers SquibbJames J. Devenny - Bristol-Myers SquibbSuzanne Rooney - Bristol-Myers SquibbMichael Thomas - Bristol-Myers SquibbSusan Glick - Bristol-Myers SquibbHelen E. Godonis - Bristol-Myers SquibbSusan J. Harvey - Bristol-Myers SquibbMary Jane Cullen - Bristol-Myers SquibbHongwei Zhang - Bristol-Myers SquibbChristian Caporuscio - Bristol-Myers SquibbPaul Stetsko - Bristol-Myers SquibbMary Grubb - Bristol-Myers SquibbBrad D. Maxwell - Bristol-Myers SquibbHong Yang - Bristol-Myers SquibbAtsu Apedo - Bristol-Myers SquibbBrian Gemzik - Bristol-Myers SquibbEvan B. Janovitz - Bristol-Myers SquibbChristine Huang - Bristol-Myers SquibbLisa Zhang - Bristol-Myers SquibbChris Freeden - Bristol-Myers SquibbBrian J. Murphy - Bristol-Myers Squibb
- Publication Details
- Journal of medicinal chemistry, v 57(18), pp 7509-7522
- Publisher
- Amer Chemical Soc
- Number of pages
- 14
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000342396200003
- Scopus ID
- 2-s2.0-84907486545
- Other Identifier
- 991021902526104721
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InCites Highlights
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- Web of Science research areas
- Chemistry, Medicinal