Structure-activity relationships (SAR) and structure-kinetic relationships (SKR) of bicyclic heteroaromatic acetic acids as potent CRTh2 antagonists II: lead optimization.

Authors :: Alonso JA
Andrés M
Bravo M
Calbet M
Eastwood PR
Eichhorn P
Esteve C
Ferrer M
Gómez E
González J
Mir M
Moreno I
Petit S
Roberts RS
Sevilla S
Vidal B
Vidal L
Vilaseca P
Zanuy M
Source :: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2014 Nov 01; Vol. 24 (21), pp. 5123-6. Date of Electronic Publication: 2014 Aug 19.
Publication Year :: 2014
Abstract: Extensive structure-activity relationship (SAR) and structure-kinetic relationship (SKR) studies in the bicyclic heteroaromatic series of CRTh2 antagonists led to the identification of several molecules that possessed both excellent binding and cellular potencies along with long receptor residence times. A small substituent in the bicyclic core provided an order of magnitude jump in dissociation half-lives. Selected optimized compounds demonstrated suitable pharmacokinetic profiles.<br /> (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Subjects :: Acetates chemical synthesis
Acetates pharmacokinetics
Animals
Half-Life
Humans
Indoles chemistry
Injections, Intravenous
Rats
Rats, Wistar
Receptors, Immunologic metabolism
Receptors, Prostaglandin metabolism
Structure-Activity Relationship
Acetates chemistry
Bridged Bicyclo Compounds chemistry
Receptors, Immunologic antagonists & inhibitors
Receptors, Prostaglandin antagonists & inhibitors

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