Inhibition of cholesterol side-chain cleavage. 3. 22-Azacholesterol analogs bearing aryl-substituted side chains

• Published in: Journal of medicinal chemistry Vol. 24; no. 9; pp. 1034 - 1038
• Main Authors: Delaney, Norma G, Lu, Matthias C
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 01-09-1981
• Subjects: Adrenal Glands - enzymology; Animals; Cattle; Chemical Phenomena; Chemistry; Cholesterol - analogs & derivatives; Cholesterol - chemical synthesis; Cholesterol - metabolism; Cholesterol - pharmacology; In Vitro Techniques; Structure-Activity Relationship
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm00141a003

The potent inhibitory activity of 22-azacholesterol analogue 2a, in which the (3-methylbutyl)amino side chain had been replaced by the (phenylethyl)amino side chain, on the conversion of cholesterol to pregnenolone prompted the synthesis and enzymatic studies of two series of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.