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Cyclohex‐1‐ene Carboxylic Acids: Synthesis and Biological Evaluation of Novel Inhibitors of Human 5α Reductase
Author(s) -
Baston Eckhard,
Salem Ola I. A.,
Hartmann Rolf W.
Publication year - 2003
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.200390001
Subject(s) - chemistry , isozyme , stereochemistry , wittig reaction , reductase , chemical synthesis , enzyme , biological activity , biochemistry , in vitro
In search of novel nonsteroidal mimics of steroidal inhibitors of 5α reductase, 4‐(2‐phenylethyl)cyclohex‐1‐ene carboxylic acids 1 — 5 were synthesized with different substituents in para position of the phenyl ring ( 1 : N , N ‐diisopropylcarbamoyl, 2 : phenyl, 3 : phenoxy, 4 : benzoyl, and 5 : benzyl). The principal synthetic approach for the desired compounds consisted of a Wittig olefination between 1, 4‐dioxaspiro [4.5]‐decane‐8‐carbaldehyde ( 4g and the appropriate phosphonium salts. The compounds were tested for inhibition of human 5α reductase isozymes 1 and 2 using DU 145 cells and preparations from prostatic tissue, respectively. They turned out to be good inhibitors of the prostatic isozyme 2 with compound 1 being the most potent one (IC 50 = 760 nM). Isozyme 1 was only slightly inhibited. It is concluded that the novel structures are appropriate for being further optimized, aiming at the development of a novel drug for the treatment of benign prostatic hyperplasia.