Synthesis of a series of 3-cyanopropionamides and 4-imino-gamma-butyrolactams and evaluation of their function as modulators of multidrug resistance.

The synthesis of the 3-cyanopropionamides 3a and 3b, of the 2,2-dimethyl-3-cyanopropionamides 4a-4c and of the 4-imino-gamma-butyrolactams 5a and 5b (cyclic functional isomers of 3-cyanopropionamides) is described. The amides 3a and 3b were obtained by aminolysis of the corresponding acid chlorides, which are accessible via hydrolysis of the ethyl esters to the acids. This methodology was not used for the synthesis of the amides 4a-4c owing to steric hindrance to hydrolysis in the corresponding ethyl esters.