Synthesis and biological evaluation of substituted 4-(OBz)phenylalanine derivatives as novel N-type calcium channel blockers.
Selective N-type Voltage Activated Calcium Channel (VACC) blockers have shown utility in several models of stroke and pain. In the process of searching for small molecules as N-type calcium channel blockers, we have identified a series of N,N-dialkylpeptidylamines (e.g., PD 175069) with potent functional activity at N-type VACC. Further modification of the leucine moiety of PD 175069 with a cyclized ring structure provides a series of novel molecules. Syntheses and pharmacological evaluation of the series are presented.
D002121:Calcium Channel Blockers / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D006801:Humans; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D014407:Tumor Cells, Cultured