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ID: ALA3351921
Journal: Bioorg Med Chem Lett
Title: Structure-activity relationships (SAR) and structure-kinetic relationships (SKR) of pyrrolopiperidinone acetic acids as CRTh2 antagonists.
Authors: Andrés M, Buil MA, Calbet M, Casado O, Castro J, Eastwood PR, Eichhorn P, Ferrer M, Forns P, Moreno I, Petit S, Roberts RS.
Abstract: Pyrrolopiperidinone acetic acids (PPAs) were identified as highly potent CRTh2 receptor antagonists. In addition, many of these compounds displayed slow-dissociation kinetics from the receptor. Structure-kinetic relationship (SKR) studies allowed optimisation of the kinetics to give potent analogues with long receptor residence half-lives of up to 23 h. Low permeability was a general feature of this series, however oral bioavailability could be achieved through the use of ester prodrugs.
CiteXplore: 25437503