Pyrrolidinohydroquinazolines--a novel class of CCR3 modulators

Ralf Anderskewitz; Rolf Bauer; Gisela Bodenbach; Dirk Gester; Bernd Gramlich; Gerd Morschhäuser; Franz W Birke

doi:10.1016/j.bmcl.2004.11.039

Pyrrolidinohydroquinazolines--a novel class of CCR3 modulators

Bioorg Med Chem Lett. 2005 Feb 1;15(3):669-73. doi: 10.1016/j.bmcl.2004.11.039.

Authors

Ralf Anderskewitz¹, Rolf Bauer, Gisela Bodenbach, Dirk Gester, Bernd Gramlich, Gerd Morschhäuser, Franz W Birke

Affiliation

¹ Boehringer Ingelheim Pharma GmbH and Co. KG, Birkendorfer Strasse 65, D-88397 Biberach an der Riss, Germany. ralf.anderskewitz@bc.boehringer-ingelheim.com

PMID: 15664834
DOI: 10.1016/j.bmcl.2004.11.039

Abstract

A novel class of CCR3 modulators is described. Starting with lead compound 4a (K(i): 110 nM), which turned out to be an antagonist of eotaxin at the CCR3 receptor, further optimization led to compound 8b (K(i): 28 nM), which surprisingly proved to be an agonist.

MeSH terms

Calcium Signaling / drug effects
Chemokine CCL11
Chemokines, CC / antagonists & inhibitors
Eosinophils / drug effects
Humans
Quinazolines / chemical synthesis*
Quinazolines / pharmacology
Receptors, CCR3
Receptors, Chemokine / agonists
Receptors, Chemokine / antagonists & inhibitors
Receptors, Chemokine / drug effects*
Structure-Activity Relationship

Substances

CCL11 protein, human
CCR3 protein, human
Chemokine CCL11
Chemokines, CC
Quinazolines
Receptors, CCR3
Receptors, Chemokine