247174-39-6Relevant articles and documents
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.
Naphthalene derivatives, their production and use
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, (2008/06/13)
A composition containing a compound of the formula: wherein A is a nitrogen-containing heterocyclic group which may be substituted, R1 is a hydrogen atom, hydrocarbon group which may be substituted, or monocyclic aromatic heterocyclic group which may be substituted, R2 is a hydrogen atom or a lower alkyl group which may be substituted, R3, R4, R5, R6, R7, R8 and R9 are independently a hydrogen atom, a hydrocarbon group which may be substituted, a hydroxy group which may be substituted, a thiol group which may be substituted, an amino group which may be substituted, an acyl group or a halogen atom, a salt thereof or a prodrug thereof has steroid C17,20-lyase inhibitory activity, and is useful for preventing and treating for example, primary cancer of malignant tumor, its metastasis and recurrence thereof.
