Synthesis and 5 alpha-reductase inhibitory activity of 8-substituted benzo[f]quinolinones derived from palladium mediated coupling reactions.
Benzoquinolinones have been shown to be potent, selective inhibitors of the Type I 5 alpha-reductase enzyme, which is responsible for the production of dihydrotestosterone from testosterone localized in the scalp. In an effort to identify compounds that demonstrate inhibition of both 5 alpha-reductase isozymes, we have employed 8-bromobenzoquinolinone as an advanced intermediate for participation in a variety of palladium mediated carbon-carbon bond forming reactions. By varying the 8-substituent it is possible to alter the selectivity profile of the series.
Smith
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Lilly Research Laboratories, Division of Eli Lilly and Company, Indianapolis, IN 46285, USA.
McQuaid
L A
LA
Goode
R L
RL
McNulty
A M
AM
Neubauer
B L
BL
Rocco
V P
VP
Audia
J E
JE
D042944:Cholestenone 5 alpha-Reductase; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008297:Male; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D010165:Palladium / Q000737:chemistry*; D011467:Prostate / Q000187:drug effects / Q000201:enzymology; D015363:Quinolones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D012535:Scalp / Q000187:drug effects / Q000201:enzymology; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D015363:Quinolones; D010165:Palladium; D010088:Oxidoreductases; D042944:Cholestenone 5 alpha-Reductase