Pyrrolidinohydroquinazolines--a novel class of CCR3 modulators.
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.
Anderskewitz
Ralf
R
Boehringer Ingelheim Pharma GmbH and Co. KG, Birkendorfer Strasse 65, D-88397 Biberach an der Riss, Germany. ralf.anderskewitz@bc.boehringer-ingelheim.com
Bauer
Rolf
R
Bodenbach
Gisela
G
Gester
Dirk
D
Gramlich
Bernd
B
Morschhäuser
Gerd
G
Birke
Franz W
FW
D020013:Calcium Signaling / Q000187:drug effects; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000037:antagonists & inhibitors; D004804:Eosinophils / Q000187:drug effects; D006801:Humans; D011799:Quinazolines / Q000138:chemical synthesis* / Q000494:pharmacology; D054397:Receptors, CCR3; D019707:Receptors, Chemokine / Q000819:agonists / Q000037:antagonists & inhibitors / Q000187:drug effects*; D013329:Structure-Activity Relationship
C515456:CCL11 protein, human; C515350:CCR3 protein, human; D054413:Chemokine CCL11; D019742:Chemokines, CC; D011799:Quinazolines; D054397:Receptors, CCR3; D019707:Receptors, Chemokine