Yu, Ming; Lizarzaburu, Mike; Motani, Alykhan; Fu, Zice; Du, Xiaohui; Liu, Jiwen; Jiao, Xianyun; Lai, SuJen; Fan, Peter; Fu, Angela; Liu, Qingxiang; Murakoshi, Michiko; Nara, Futoshi; Oda, Kozo; Okuyama, Ryo; Reagan, Jeff D.; Watanabe, Nobuaki; Yamazaki, Mami; Xiong, Yumei; Zhang, Ying; Zhuang, Run; Lin, Daniel C.-H.; Houze, Jonathan B.; Medina, Julio C.; Li, Leping published the article 《Aminopyrazole-Phenylalanine Based GPR142 Agonists: Discovery of Tool Compound and in Vivo Efficacy Studies》. Keywords: amrinone phenylalanine carboxylic acid preparation GPR142 agonist structure design; pharmacokinetics bioavailability diabetes amrinone phenylalanine carboxylic acid antidiabetic prodrug; glucose tolerance insulin secretagogue human islet transplant CYP450 hERG; GPR142 agonist; aminopyrazole−phenylalanine; human islet transplant; insulin secretagogue; oral glucose tolerance test; prodrug; type 2 diabetes.They researched the compound: 3-(Pyridin-4-yl)-1H-pyrazol-5-amine( cas:91912-53-7 ).Reference of 3-(Pyridin-4-yl)-1H-pyrazol-5-amine. Aromatic heterocyclic compounds can be divided into two categories: single heterocyclic and fused heterocyclic. In addition, there is a lot of other information about this compound (cas:91912-53-7) here.
Herein, we report the lead optimization of amrinone-phenylalanine based GPR142 agonists. Structure-activity relationship studies led to the discovery of aminopyrazole-phenylalanine carboxylic acid I, which exhibited good agonistic activity, high target selectivity, desirable pharmacokinetic properties, and no cytochrome P 450 or hERG liability. Compound I, together with its orally bioavailable Et ester prodrug II, were found to be suitable for in vivo proof-of-concept studies. Compound II displayed good efficacy in a mouse oral glucose tolerance test (OGTT). CompoundI showed GPR142 dependent stimulation of insulin secretion in isolated mouse islets and demonstrated a statistically significant glucose lowering effect in a mouse model bearing transplanted human islets.
There is still a lot of research devoted to this compound(SMILES：NC1=CC(C2=CC=NC=C2)=NN1)Reference of 3-(Pyridin-4-yl)-1H-pyrazol-5-amine, and with the development of science, more effects of this compound(91912-53-7) can be discovered.