1599479-01-2Relevant academic research and scientific papers
Design, synthesis, and evaluation of novel and selective G-protein coupled receptor 120 (GPR120) spirocyclic agonists
Cox, Jason M.,Chu, Hong D.,Chelliah, Mariappan V.,Debenham, John S.,Eagen, Keith,Lan, Ping,Lombardo, Matthew,London, Clare,Plotkin, Michael A.,Shah, Unmesh,Sun, Zhongxiang,Vaccaro, Henry M.,Venkatraman, Srikanth,Suzuki, Takao,Wang, Nengxue,Ashley, Eric R.,Crespo, Alejandro,Madeira, Maria,Leung, Dennis H.,Alleyne, Candice,Ogawa, Aimie M.,Souza, Sarah,Thomas-Fowlkes, Brande,Di Salvo, Jerry,Weinglass, Adam,Kirkland, Melissa,Pachanski, Michele,Powles, Mary Ann,Tozzo, Effie,Akiyama, Taro E.,Ujjainwalla, Feroze,Tata, James R.,Sinz, Christopher J.
, p. 49 - 54 (2017/12/12)
Type 2 diabetes mellitus (T2DM) is an ever increasing worldwide epidemic, and the identification of safe and effective insulin sensitizers, absent of weight gain, has been a long-standing goal of diabetes research. G-protein coupled receptor 120 (GPR120) has recently emerged as a potential therapeutic target for treating T2DM. Natural occurring, and more recently, synthetic agonists have been associated with insulin sensitizing, anti-inflammatory, and fat metabolism effects. Herein we describe the design, synthesis, and evaluation of a novel spirocyclic GPR120 agonist series, which culminated in the discovery of potent and selective agonist 14. Furthermore, compound 14 was evaluated in vivo and demonstrated acute glucose lowering in an oral glucose tolerance test (oGTT), as well as improvements in homeostatic measurement assessment of insulin resistance (HOMA-IR; a surrogate marker for insulin sensitization) and an increase in glucose infusion rate (GIR) during a hyperinsulinemic euglycemic clamp in diet-induced obese (DIO) mice.
SUBSTITUTED SPIROPIPERIDINYL COMPOUNDS USEFUL AS GPR120 AGONISTS
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Page/Page column 42; 43, (2014/05/07)
The present invention relates to a compound represented by formula (I): and pharmaceutically acceptable salts thereof are disclosed as useful for treating or preventing diabetes, hyperlipidemia, obesity, inflammation related disorders, and related diseases and conditions. The compounds are useful as agonists of the G-protein coupled receptor GPR120. Pharmaceutical compositions and methods of treatment are also included.
