Structure-activity relationships of substituted 1-pyridyl-2-phenyl-1,2-ethanediones: potent, selective carboxylesterase inhibitors.
Structure-activity relationships of substituted 1-pyridyl-2-phenyl-1,2-ethanediones: potent, selective carboxylesterase inhibitors.
复制标题
DOI：
10.1021/jm101101q
复制
发表时间：
2010-12-23
影响因子：
7.3
通讯作者：
Webb TR
中科院分区：
文献类型：
--
作者：
Young BM;Hyatt JL;Bouck DC;Chen T;Hanumesh P;Price J;Boyd VA;Potter PM;Webb TR
肠道羧酸酯酶的抑制可能会通过改变半衰期或毒性来改变现有药物的药代动力学/药效学特征。由于先前鉴定的二芳基乙烷-1，2-二酮抑制剂明显是疏水性的，因此设计了修饰的二酮支架并将其加工成>300个成员的文库，随后对其进行筛选以建立酯酶抑制的SAR。这使得能够鉴定出在选择性和测量的溶解度方面均显示出改善的个位数纳摩尔hiCE抑制剂。
Inhibition of intestinal carboxylesterases may allow modification of the pharmacokinetics/pharmacodynamic profile of existing drugs by altering half-life or toxicity. Since previously identified diaryl ethane-1,2-dione inhibitors are decidedly hydrophobic, a modified dione scaffold was designed and elaborated into a >300 member library, which was subsequently screened to establish the SAR for esterase inhibition. This allowed the identification of single digit nanomolar hiCE inhibitors that showed improvement in both selectivity and measured solubility.
登录
查看更多内容
影响因子：
5.8
作者：
ELLMAN, GL;COURTNEY, KD;FEATHERSTONE, RM
通讯作者：
FEATHERSTONE, RM
影响因子：
5.2
作者：
Netherton, MR;Fu, GC
通讯作者：
Fu, GC
影响因子：
7.3
作者：
Hyatt, JL;Stacy, V;Potter, PM
通讯作者：
Potter, PM
影响因子：
5.2
作者：
Deng, XH;Mani, NS
通讯作者：
Mani, NS
影响因子：
7.3
作者：
Hicks LD;Hyatt JL;Stoddard S;Tsurkan L;Edwards CC;Wadkins RM;Potter PM
通讯作者：
Potter PM