Basic Information
ID: ALA5131553
Journal: ACS Med Chem Lett
Title: Novel 6-Methoxy-3,4-dihydro-1H-isoquinoline Compounds for Treating Diabetes.
Authors: Sabnis RW.
Abstract: Polar molecular surface area provides a valuable metric when optimizing properties as varied as membrane permeability and efflux susceptibility. The EPSA method to measure this quantity has had a substantial impact in medicinal chemistry, providing insight into the conformational and stereoelectronic features that govern the polarity of small molecules, targeted protein degraders, and macrocyclic peptides. Recognizing the value of bioisosteres in replacing permeation-limiting polar groups, we determined the effects of common amide, carboxylic acid, and phenol bioisosteres on EPSA, using matched molecular pairs within the Merck compound collection. Our findings reinforce EPSA's utility in optimizing permeability, highlight bioisosteres within each class that are particularly effective in lowering EPSA and others, which despite widespread use, offer little to no such benefit. Our method for matched-pair identification is generalizable across large compound collections and, thus, may constitute a flexible platform to study the effects of bioisosterism both in EPSA and other in vitro assays.
CiteXplore: 35707151
DOI: 10.1021/acsmedchemlett.2c00220
Patent ID: ┄
Associated Items: Associated Bioactivities Associated Assays Associated Compounds Associated Targets