An oxidation product (5) formed during the synthesis of BIBN-4096BS (1) was found to be a potent CGRP antagonist (IC50=0.11nM). While 5 was found to be ten-fold less potent than 1, another analog 8 with lower molecular weight containing the oxidized fragment demonstrated twenty-fold higher activity than its parent 7.
View Article and Find Full Text PDF[structures: see text] A stereocontrolled racemic synthesis of conformationally restricted analogues 2a and 2b of a potent CGRP receptor antagonist 1 by novel functionalization of 2-substituted octahydropyrido[1,2-a]pyrazin-6-ones is described. The new diastereoselective LDA-promoted alpha-nitration of intermediate lactams established the required trans-configuration in the desired products.
View Article and Find Full Text PDFThe present studies have identified a series of diaminopyrimidines and diaminopyridines as novel 5-HT(7) receptor ligands. Three regiosiomeric classes of pyrimidines and four regioisomeric classes of pyridines were synthesized and analyzed for binding to the 5-HT(7) receptor. The 5-HT(7) binding affinities of different regioisomers show clearly the structure-activity relationship with position of ring nitrogens.
View Article and Find Full Text PDF