Combinatorial synthesis and screening of a chemical library of 1,4-dihydropyridine calcium channel blockers.
Solid-phase synthesis of a 300-member pharmacophore library of 1,4-dihydropyridines from keto ester, diketone and aldehyde building blocks on a cleavable amine polymeric support is described. Screening and serial deconvolution of the combinatorial library has resulted in identification of known and new potent calcium channel blockers.
Gordeev
M F
MF
Affymix Research Institute, Santa Clara, CA 95051, USA.
Patel
D V
DV
England
B P
BP
Jonnalagadda
S
S
Combs
J D
JD
Gordon
E M
EM
D000818:Animals; D001667:Binding, Competitive; D002121:Calcium Channel Blockers / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D004095:Dihydropyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D066298:In Vitro Techniques; D009568:Nitrendipine / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004095:Dihydropyridines; C038806:1,4-dihydropyridine; D009568:Nitrendipine