Inhibition of cholesterol side-chain cleavage. 4. Synthesis of A or B ring modified azacholesterols

A number of A or B ring modified 20- and 22-azacholesterol analogues (1 and 2, respectively) were synthesized in an attempt to ascertain the structural requirements for inhibition of the cholesterol side-chain cleavage reaction in bovine adrenocortical mitochondrial acetone powder preparations. The inhibition studies of these analogues revealed that (1) the 3-methyl ethers were as active as the parent compounds and that (2) reduction of the delta 5 double bond greatly lessened the inhibitory activity. These studies demonstrated a crucial role of the delta 5 double bond for inhibitory activity, while a free hydroxyl group at C-3 is not essential for this action. Furthermore, as in the parent compounds, 22-azacholesterol analogues were more potent than their 20-azacholesterol counterparts.