Inhibition of cholesterol side-chain cleavage. Part 5. Synthesis of 22-(p-chlorophenyl) cholesterol analogues.
Three 22-(p-chloroaryl) analogues of cholesterol (6a-c) were synthesized and evaluated as potential inhibitors of the adrenal cholesterol side-chain cleavage enzyme, in comparison with the known 20-aryl analogue, 20-(p-chlorophenyl)-5-prenen-3 beta,20-diol (2b). All were potent inhibitors. An oxygen at C-22 (analogues 6a and 6b) enhanced the strong binding to the enzyme. Two compounds (6b and 6c) are potential substrates of the enzyme. Possible pharmaceutical uses for these compounds and their derivatives are discussed.
Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois, Chicago 60612.
C P
CP
Bergstrom
R
R
Clarke
J F
JF
Fitzloff
M C
MC
Lu
D000311:Adrenal Glands / Q000187:drug effects / Q000201:enzymology; D000818:Animals; D002417:Cattle; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000037:antagonists & inhibitors* / Q000378:metabolism; D066298:In Vitro Techniques; D011284:Pregnenolone / Q000378:metabolism
D011284:Pregnenolone; D002784:Cholesterol; D002786:Cholesterol Side-Chain Cleavage Enzyme