Scott B. Meikrantz

4-Isoxazolyl-1,4-dihydropyridines exhibit binding at the multidrug resistance transporter

The 4-isoxazolyl-dihydropyridines (IDHPs) exhibit inhibition of the multidrug-resistance transporter (MDR-1), and exhibit an SAR distinct from their activity at voltage gated calcium channels (VGCC). Among the four most active IDHPs, three were branched at C-5 of the isoxazole, including the most active analog, 1k.

Improved Routes to Homologated Isoxazoles

Abstract Two carbon homologation of isoxazole-4-carbinols was performed by reaction of lithio-2,4,4-trimethyl-δ2-oxazoline 1 with 4-chloromethyl-isoxazole 2, followed by trans-esterification and reduction to the isoxazole-4-propanols 5a and b. Alternatively, 2,4-diketones 6 were alkylated with 1-bromo-3-chloro-propane, and the chloro ketones 7 treated with hydroxylamine to give isoxazole-4-propanols, 5a-c.