分类: 物理学 >> 普通物理:统计和量子力学,量子信息等 提交时间: 2017-11-17
摘要: A new chemical class of potent DPP-IV inhibitors has been structurally derived from our recently disclosed pyrrolopyrimidine scaffold by replacing cyanobenzyl with butynyl group. Systematic variations and structure-activity relationship studies have been conducted on the starting hit 51 (IC50= 0.46 μM). Consequently, compound 78 (IC50= 1.55 nM) was identified to be a potent, selective, and orally available lead, worth further evaluations and optimizations.
分类: 物理学 >> 普通物理:统计和量子力学,量子信息等 提交时间: 2017-11-17
摘要: The structural superposition of DPP-IV complex with Alogliptin and Linagliptin displayed a similar binding mode. The butynyl of Linagliptin and cyanobenzyl of Alogliptin occupy the S1 pocket which therefore could be mutually switched. Thus a pharmacophore hybridization of Alogliptin was initiated and led to a novel DPP-IV inhibitor 61. Though it did not exhibit desired activity (IC50= 0.2 礛), the butynyl compound acts as a lead compound triggered a following structural optimization. A novel series of potent DPP-IV inhibitors represented by compound 77 (IC50= 0.36 nM) were obtained with a robust pharmacokinetic profile and better in vitro and in vivo efficacy than Alogliptin.
分类: 生物学 >> 生态学 提交时间: 2017-11-17
摘要: It is urgent to discover new anti-influenza drugs considering the threat of so called swine flu and Spanish flu. Though Adamantane derivatives are the only M2 inhibitors as anti-influenza virus A drugs, they are limited to use in the US due to drug resistant. Herein we reported that multiple lead compounds as M2 inhibitors were rapidly generated through the screening of focused library designed with scaffold-hopping strategy based on Amantadine.
分类: 生物学 >> 生态学 提交时间: 2017-11-17
摘要: The discovery of new anti-influenza drugs is urgent, particularly considering the recent threat of swine flu. Although amantadine derivatives are the only M2 drugs for influenza virus A, their use is limited in the US due to drug resistance. Here we report the discovery of multiple M2 inhibitor lead compounds that were rapidly generated through focused screening of a small primary amine library which was designed using a scaffold-hopping strategy based on amantadine.