Development of matrix metalloproteinase-13 inhibitors - A structure-activity/structure-property relationship study.

ABSTRACT: A structure-activity/structure-property relationship study based on the physicochemical as well as in vitro pharmacokinetic properties of a first generation matrix metalloproteinase (MMP)-13 inhibitor (2) was undertaken. After systematic variation of inhibitor 2, compound 31 was identified which exhibited microsomal half-life higher than 20?min, kinetic solubility higher than 20??M, and a permeability coefficient greater than 20?×?10-6?cm/s. Compound 31 also showed excellent in vivo PK properties after IV dosing (Cmax?=?56.8??M, T1/2 (plasma)?=?3.0?h, Cl?=?0.23?mL/min/kg) and thus is a suitable candidate for in vivo efficacy studies in an OA animal model.

SUBMITTER: Fuerst R 

PROVIDER: S-EPMC6379921 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature