Kaku, Tomohiro; Tsujimoto, Saori; Matsunaga, Nobuyuki; Tanaka, Toshimasa; Hara, Takahito; Yamaoka, Masuo; Kusaka, Masami; Tasaka, Akihiro published the artcile< 17,20-Lyase inhibitors. Part 3: Design, synthesis, and structure-activity relationships of biphenylylmethylimidazole derivatives as novel 17,20-lyase inhibitors>, Recommanded Product: (9Z,12Z)-Methyl octadeca-9,12-dienoate, the main research area is prostate cancer lyase inhibitor biphenylylmethylimidazole preparation SAR.
A novel series of biphenylylmethylimidazole derivatives and related compounds were synthesized as inhibitors of 17,20-lyase, a key enzyme in the production of steroid hormones, and their biol. activities were evaluated. In an attempt to identify potent and selective inhibitors of 17,20-lyase over the related CYP3A4 enzyme, a homol. model for human 17,20-lyase was developed using the X-ray crystallog. structure of the mammalian CYP2C5 enzyme. With the aid of mol. modeling, optimization of the biphenyl moiety was performed to give an acetamide derivative, which was resolved by HPLC to give the active (-)-enantiomer. The obtained active enantiomer showed not only potent inhibition of both rat and human 17,20-lyase,with IC50 values of 14 and 26 nM, resp., but also excellent selectivity (>300-fold) for inhibition of 17,20-lyase over CYP3A4. Moreover, the active enantiomer significantly reduced both serum testosterone and DHEA concentrations in a monkey model after single oral administration. Asym. synthesis of the active enantiomer was also developed via a chiral intermediate using a diastereoselective Grignard reaction.
Bioorganic & Medicinal Chemistry published new progress about Diastereoselective synthesis. 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, Recommanded Product: (9Z,12Z)-Methyl octadeca-9,12-dienoate.
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