1599477-75-4

Usage

Biological Activity

gpr120 compound a is an orally active and high-affinity agonist of gpr120 [1].g-protein coupled receptor 120 (gpr120, free fatty acid receptor 4/ffar4) is a g protein-coupled receptor which has been expressed in intestine, adipocytes, and pro-inflammatory macrophages that is activated by long chain free fatty acids. gpr120 has been involved in mediating the anti-inflammatory and insulin-sensitizing effects of omega 3 fatty acids. deficiency of gpr120 is responsible for reduced fat metabolism, produce anti-inflammatory effects and to acutely potentiate insulin secretion [2].gpr120 compound a activated gpr120 with the ec50 value of ~0.35 μm. gpr120 compound a demonstrated potent selectivity over another lipid-sensing g-protein, gpr40 (ffar1). in a high-fat diet fed obese mice, gpr120 compound a (30 mg/kg) exerted anti-inflammatory effects on macrophages in vitro and improved glucose tolerance, decreased hyperinsulinemia, increased insulin sensitivity, and decreased hepatic steatosis [1].

references

[1] walenta e, akiyama t e, lagakos w s, et al. a gpr120-selective agonist improves insulin resistance and chronic inflammation in obese mice[j]. nature medicine, 2014, 20(8): 942-947.[2] ichimura a, hirasawa a, poulain-godefroy o, et al. dysfunction of lipid sensor gpr120 leads to obesity in both mouse and human[j]. nature, 2012, 483(7389): 350-354.

Upstream product

• 189333-18-4 3-oxo-9-azaspiro[5.5]undec-4-ene-9-carboxylic acid benzyl ester 
• 138163-08-3 N-(benzyloxycarbonyl)piperidine-4-carboxaldehyde 
• 1599478-96-2 benzyl 9-(2-methoxy-2-oxoethylidene)-3-azaspiro[5.5]undec-7-ene-3-carboxylate 
• 1346229-41-1 tert-butyl 9-(2-methoxy-2-oxoethyl)-3-azaspiro[5.5]undecane-3-carboxylate 
• 1599478-97-3 methyl 2-(3-(2-chloro-5-(trifluoromethoxy)phenyl)-3-azaspiro[5.5]undecan-9-yl)acetate 
• 1017623-70-9 methyl 2-(3-azaspiro[5.5]undecan-9-yl)acetate 

Downstream Products

• 1599478-33-7 C₁₉H₂₅ClF₃NO₂ 
• 1599478-77-9 2-(3-(2-chloro-5-(trifluoromethoxy)phenyl)-3-azaspiro[5.5]undecan-9-yl)ethanamine 
• 1599479-15-8 C₂₀H₂₇ClF₃NO₄S 
• 1599479-17-0 C₁₉H₂₄ClF₃N₄O 

Relevant academic research and scientific papers

Design, synthesis, and evaluation of novel and selective G-protein coupled receptor 120 (GPR120) spirocyclic agonists

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

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.