1026063-71-7Relevant academic research and scientific papers
Identification of a nonbasic melanin hormone receptor 1 antagonist as an antiobesity clinical candidate
Washburn, William N.,Manfredi, Mark,Devasthale, Pratik,Zhao, Guohua,Ahmad, Saleem,Hernandez, Andres,Robl, Jeffrey A.,Wang, Wei,Mignone, James,Wang, Zhenghua,Ngu, Khehyong,Pelleymounter, Mary Ann,Longhi, Daniel,Zhao, Rulin,Wang, Bei,Huang, Ning,Flynn, Neil,Azzara, Anthony V.,Barrish, Joel C.,Rohrbach, Kenneth,Devenny, James J.,Rooney, Suzanne,Thomas, Michael,Glick, Susan,Godonis, Helen E.,Harvey, Susan J.,Cullen, Mary Jane,Zhang, Hongwei,Caporuscio, Christian,Stetsko, Paul,Grubb, Mary,Maxwell, Brad D.,Yang, Hong,Apedo, Atsu,Gemzik, Brian,Janovitz, Evan B.,Huang, Christine,Zhang, Lisa,Freeden, Chris,Murphy, Brian J.
, p. 7509 - 7522 (2015/01/09)
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).
