Steroidal carbonitriles as potential aromatase inhibitors

Abstract Estrogens, responsible for the growth of hormone-dependant breast cancer are biosynthesized from androgens involving aromatase enzyme in the last rate limiting step. Inhibition of aromatase is an efficient approach for the prevention and treatment of breast cancer. Novel 4-phenylthia derivatives ( 2, 3 and 7 ) have been synthesized as aromatase inhibitors. The synthesized compounds ( 2, 3 and 7 ) exhibited noticeable enzyme inhibiting activity. Kinetics study of these compounds ( 2 , 3 , and 7 ) showed negligible inhibition of the enzyme under conditions conducive for irreversible inhibition of the enzyme. Introduction of unsaturation at C-4, C-1 & 4 or C-4 & 6 (compounds 5, 9 and 11 ) was observed to not be an effective strategy for entrancing aromatase inhibiting activity in 17-oxo-16β-carbonitrile derivatives. The d -seco derivatives ( 13–15 and 17 ) having unsaturation at C-4, C-1 & 4 or C-4 & 6 along with carbonitrile function in ring-D showed complete loss of aromatase inhibiting activity.