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.
D000311:Adrenal Glands / Q000201:enzymology; D000818:Animals; D002417:Cattle; D055598:Chemical Phenomena; D002621:Chemistry; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology; D066298:In Vitro Techniques
C032414:20-azacholesterol; C032413:22-azacholesterol; D002784:Cholesterol