Inhibition of cholesterol side-chain cleavage. 3. 22-azacholesterol analogues bearing aryl-substituted side chains.
The potent inhibitory activity of 22-azacholesterol analogue 2a, in which the (3-methylbutyl)amino side chain had been replaced by the (phenylethyl)amino side chain, on the conversion of cholesterol to pregnenolone prompted the synthesis and enzymatic studies of two series of 22-azacholesterol analogues bearing (arylalkyl)amino and (arylalkyl)amino side chains. The potent inhibitory activity of both the amines (2) and the amides (3) indicated that a basic nitrogen was not a requirement for inhibitory activity. However, the amide analogue (4) in which the positions of the carbonyl and the nitrogen were interchanged was a much poorer inhibitor. The inhibitory activities in the phenylacetamido series were decreased by electron-withdrawing groups on the aromatic ring, while an electron-donating group effected a small increase.
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; D013329:Structure-Activity Relationship
C032413:22-azacholesterol; D002784:Cholesterol