Branched-Chain Carbon Compounds. Part 6. Synthesis of a Series of3-Cyanopropionamides and 4-Imino-γ-butyrolactams and Evaluationof Their Function as Modulators of Multidrug Resistance.

Abstract

Cyanopropionamides like (VII), (XI), and (XV) are prepared as well as theheavily substituted lactam (XIII) in an unplanned way. With a view tosynthesizing a pyridyl propionamide, the ester (IIIb) and the acid (IVb) areprepared. However, treatment of (IVb) with thionyl chloride gives a crudeblack solid. The alkylation of (VIIIa) with (IX) is improved by using potassiumtert-butoxide as base in HMPA. The branched chain amides (XIa) and (XV),and lactam (XIII) are active in the multidrug resistance cells. Lactam (XIII)reduces the vineristine resistance by 90% at a micromolar concentration.