Synthesis and biological evaluation of isoxazole, oxazole, and oxadiazole containing heteroaryl analogs of biaryl ureas as DGAT1 inhibitors

Hypolipidemic effect of dihydroisoquinoline oxaziridine in high-fat diet-fed rats

“…In clinical terms, a surrogate decision-maker for body fat content is the body mass index (BMI), which exceeds 30 kg/m 2 called obesity [1][2][3][4].…”

Synthesis and Diacylglycerol Acyltransferase‐1 Inhibition of Azabicyclo[3.1.0]hexane Derivatives

“…Amino acid extension of the acid part for effective DGAT‐1 inhibition has been reported previously . And we introduced amino acid groups, and analogs were synthesized by the synthetic route outlined in Scheme .…”

Therapeutic Strategies for Metabolic Diseases: Small‐Molecule Diacylglycerol Acyltransferase (DGAT) Inhibitors

“…[27,28,104] Bayer Healthcare has revealed a number of molecules as DGAT-1 inhibitors that have relatively high molecular weights and enzyme activities at the hundred-nanomolar level. [108] Kwak et al developed a series of benzimidazole derivatives with a phenylcyclohexyl acetic acid group as DGAT-1 inhibitors. [25,105] In a continued effort to find safe and effective DGAT-1 inhibitors, Yun et al identified 2-phenyloxazole-4-carboxamide as a conformationally constrained analogue of a hydrazide hit (IC 50 = 0.23 mm), which was previously identified by HTS.…”

“…The compound shown in Figure 24 (IC 50 = 64 nm with an in vivo plasma TAG reduction of 90 % and a solubility of 0.43 mg mL À1 at pH 7.4) may serve as a new lead for developing novel anti-obesity and anti-diabetic agents. [108] Kwak et al developed a series of benzimidazole derivatives with a phenylcyclohexyl acetic acid group as DGAT-1 inhibitors. Among the benzimidazole series, the compound shown in Figure 25 showed sub-micromolar in vitro activity toward human and murine DGAT-1 with good selectivity against DGAT-2, human liver metabolic stability, and PK and safety profiles such as hERG, CYP, and acute toxicity.…”