430472-50-7Relevant academic research and scientific papers
17,20-Lyase inhibitors. Part 4: Design, synthesis and structure-activity relationships of naphthylmethylimidazole derivatives as novel 17,20-lyase inhibitors
Kaku, Tomohiro,Matsunaga, Nobuyuki,Ojida, Akio,Tanaka, Toshimasa,Hara, Takahito,Yamaoka, Masuo,Kusaka, Masami,Tasaka, Akihiro
, p. 1751 - 1770 (2011/04/17)
A novel series of naphthylmethylimidazole derivatives and related compounds have been investigated as selective 17,20-lyase inhibitors. Optimization of the substituent at the 6-position on the naphthalene ring was performed to yield a methylcarbamoyl derivative, which exhibited potent inhibitory activity against human 17,20-lyase and promising selectivity (>200-fold) for 17,20-lyase over CYP3A4. Further modifications of the methylcarbamoyl derivative led to the discovery of the corresponding tricyclic compound, which showed highly potent activity against human 17,20-lyase (IC50 19 nM) and good selectivity (>1000-fold) for inhibition of 17,20-lyase over CYP3A4. Additional biological evaluation revealed that the tricyclic compound had potent in vivo efficacy in monkeys and favorable pharmacokinetic profiles when administered in rats. Asymmetric synthesis of the selective tricyclic inhibitor was also achieved using a chiral α-hydroxy ketone.
IMIDAZOLE DERIVATIVES, PROCESS FOR THEIR PREPARATION AND THEIR USE
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, (2008/06/13)
The present invention provides a compound having a steroid C17,20-lyase inhibitory activity, which is useful as a prophylactic or therapeutic agent of prostatism and tumor such as breast cancer and the like. A compound represented by the formula: or wherein R is a hydrogen atom or a protecting group, R1 is a lower alkyl group or a cyclic alkyl group, and ring A and ring B are each an optionally substituted 5-membered or 6-membered ring having an amide bond in the ring, or a salt thereof.
