Biphenyls as surrogates of the steroidal backbone. Part 2: discovery of a novel family of non-steroidal 5-alpha-reductase inhibitors.
A new family of non-steroidal 5-alpha-reductase inhibitors was designed by replacing the steroid skeleton of an inhibitor related to estrone by a biphenyl moiety. This hypothesis originated from the reported estrogenic activity of a few biphenyl compounds (see Part 1 of this paper; Lesuisse et al. Bioorg. Med. Chem. Lett. 2001, 11, 1709). Two compounds turned out to be potent type 2 5-alpha-reductase inhibitors with IC(50)'s of inhibition in the nanomolar range. These are to our knowledge amongst the most potent non-steroidal 5-alpha-reductase inhibitors described to date.
Lesuisse
D
D
Medicinal Chemistry, Aventis, 102 route de Noisy, 93235 Cedex, Romainville, France. dominique.lesuisse@aventis.com
Gourvest
J F
JF
Albert
E
E
Doucet
B
B
Hartmann
C
C
Lefrançois
J M
JM
Tessier
S
S
Tric
B
B
Teutsch
G
G
D058891:5-alpha Reductase Inhibitors; D001713:Biphenyl Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D013256:Steroids / Q000737:chemistry*; D013329:Structure-Activity Relationship
D058891:5-alpha Reductase Inhibitors; D001713:Biphenyl Compounds; D004791:Enzyme Inhibitors; D013256:Steroids