Yang, Lingyun; Zhang, Jian; Si, Lianghui; Han, Li; Zhang, Bo; Ma, Hui; Xing, Junhao; Zhao, Leilei; Zhou, Jinpei; Zhang, Huibin published the artcile< Synthesis and biological evaluation of GPR40/FFAR1 agonists containing 3,5-dimethylisoxazole>, Reference of 188813-04-9, the main research area is dimethylisoxazolyl benzyloxy fluorophenylpropanoic acid preparation antidiabetic activity SAR; 3,5-Dimethylisoxazole; Diabetes; GPR40 agonist; Oral glucose tolerance test.
GPR40 is an attractive target due to its glucose-stimulated insulin secretion effect with low risk of causing hypoglycemia, which also can be seen from the clin. studies using TAK-875 (fasiglifam). 3,5-Dimethylisoxazolyl-substituted arylmethoxy fluorobenzenepropanoic acids such as I (R = Me, Et, n-Pr, i-Pr, Bu, i-Bu, cyclopropylmethyl, cyclopentyl; R1 = H, Me, F, Cl, CF3, RO; R2 = F, Cl, MeO; R3 = F, R4 = F, Cl, MeO) were prepared as GPR40 agonists; I (R1 = R2 = R3 = H; R4 = Cl) (II) was a GPR40 agonist with an EC50 value of 15.9 nM. Moreover, II reduced glucose excursion to 23.1% in ICR mice and 29.5% in type 2 diabetic C57BL/6 mice at 30 mg/kg and exhibited satisfactory pharmacokinetics profile. Mol. docking studies of I (R1 = R2 = R3 = R4 = H) with GPR40 were conducted to explain the interaction mode of this series. II with robust efficacy in vitro and in vivo constitutes a promising antidiabetic drug candidate.
European Journal of Medicinal Chemistry published new progress about Antidiabetic agents. 188813-04-9 belongs to class bromides-buliding-blocks, and the molecular formula is C8H7BrO, Reference of 188813-04-9.
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary