Xie, Hui; Zeng, Shaogao; He, Yuwen; Zhang, Guicheng; Yu, Pengjiu; Zhong, Guifa; Xu, Hongjiang; Yang, Ling; Wang, Shanchun; Zhao, Xin; Hu, Wenhui published the artcile< Rapid generation of a novel DPP-4 inhibitor with long-acting properties: SAR study and PK/PD evaluation>, SDS of cas: 2382-10-7, the main research area is DPP4 inhibitor pyrrolopyrimidine derivative preparation diabetes; DPP-4 inhibitor; In vivo efficacy; Long-acting; SAR; Type 2 diabetes.
Drug compliance is critical for patients with chronic diseases such as diabetes. In our continuous effort to find better glucose-lowering agents, an exploration for long-acting DPP-4 inhibitors had been launched. Based on our previously reported compounds bearing a pyrrolopyrimidine scaffold, the lead compound 4a (IC50 = 2.3 nM, t1/2(rat) = 5.46 h) with pharmacokinetic superiority was rapidly determined Further SAR study indicated that the pyrrole ring was generally tolerable for variation, in which a β-substitution gave a better DPP-4 affinity. In depth evaluation of the pyrrole ring β position identified a highly potent compound 12a (IC50 = 0.76 nM, t1/2(rat) = 7.89 h). In vivo pharmacodynamics tests demonstrated similar or even slightly better sustained DPP-4 inhibition for compounds 4a and 12a compared with the first marketed once-weekly drug trelagliptin in this category, indicating that improvements to DPP-4 inhibitory activity or pharmacokinetic profile might be feasible ways to rapidly generate long-acting DPP-4 inhibitors.
European Journal of Medicinal Chemistry published new progress about Antidiabetic agents. 2382-10-7 belongs to class chlorides-buliding-blocks, and the molecular formula is C6H4Cl2N4, SDS of cas: 2382-10-7.
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics