INHIBITION OF PYRIDINE-NUCLEOTIDE-DEPENDENT ENZYMES BY PYRAZOLES. SYNTHESIS AND ENZYMOLOGY OF A NOVEL A-RING PYRAZOLE STEROID

Article abstract of DOI:10.1016/0039-128X(86)90004-8

A novel A-ring pyrazole steroid, 2,3-bisaza-A-nor-1,5(10)-estradien-17β-ol (3), was synthesized as a potential inhibitor of steroidal NAD(P)H-dependent oxidoreductases.Compound (3) proved to be a potent inhibitor of 3(17)β-hydroxysteroid dehydrogenase (from P. testosteroni) exhibiting a K_i of 90 +/- 20 nM.The activities of 3α,20β-hydroxysteroid dehydrogenase (from S. hydrogenans), steroid-5α-reductase (from rat prostate), and 3α-hydroxysteroid dehydrogenase (from rat liver) were unaffected by pyrazole (3).Dead end inhibition studies indicate an ordered binding of cofactor prior to substrate or pyrazole inhibitor.