中国药物化学杂志
中國藥物化學雜誌
중국약물화학잡지
Chinese Journal of Medicinal Chemistry
2002年
2期
97-102
,共6页
苗及%凌仰之%雷小平%李洁%Angela M.H.Brodie
苗及%凌仰之%雷小平%李潔%Angela M.H.Brodie
묘급%릉앙지%뢰소평%리길%Angela M.H.Brodie
17-(5′-异唑基)雄甾-4,16-二烯-3-酮%前列腺癌%抑制剂%P45017α羟化酶和5α-还原酶
17-(5′-異唑基)雄甾-4,16-二烯-3-酮%前列腺癌%抑製劑%P45017α羥化酶和5α-還原酶
17-(5′-이서기)웅치-4,16-이희-3-동%전렬선암%억제제%P45017α간화매화5α-환원매
17-(5′-isoxazolyl)androst-4,16-dien-3-one%prostate cancer%inhibitor%17α-hydroxylase/C17,20-lyase and 5α-reductase
17-(5′-异唑基)雄甾-4,16-二烯-3-酮(4,L-39)是最有希望的P45017α和5α-还原酶的双重抑制剂,对前列腺癌及前列腺肥大具有潜在的治疗作用.对其合成路线进行改进,收率极大提高.首先,Claisen缩合物2用羟胺在乙醇中环和得到纯5′-异唑3a,用Swern氧化反应直接氧化3a,然后在在酸中异构化后得到L-39(4).或者,化合物2在无水甲酸中与羟胺环和得到3-甲酯物(6),后者以改良奥氏氧化法直接氧化生成4-烯-3-酮物(4).
17-(5′-異唑基)雄甾-4,16-二烯-3-酮(4,L-39)是最有希望的P45017α和5α-還原酶的雙重抑製劑,對前列腺癌及前列腺肥大具有潛在的治療作用.對其閤成路線進行改進,收率極大提高.首先,Claisen縮閤物2用羥胺在乙醇中環和得到純5′-異唑3a,用Swern氧化反應直接氧化3a,然後在在痠中異構化後得到L-39(4).或者,化閤物2在無水甲痠中與羥胺環和得到3-甲酯物(6),後者以改良奧氏氧化法直接氧化生成4-烯-3-酮物(4).
17-(5′-이서기)웅치-4,16-이희-3-동(4,L-39)시최유희망적P45017α화5α-환원매적쌍중억제제,대전렬선암급전렬선비대구유잠재적치료작용.대기합성로선진행개진,수솔겁대제고.수선,Claisen축합물2용간알재을순중배화득도순5′-이서3a,용Swern양화반응직접양화3a,연후재재산중이구화후득도L-39(4).혹자,화합물2재무수갑산중여간알배화득도3-갑지물(6),후자이개량오씨양화법직접양화생성4-희-3-동물(4).
17-(5′-isoxazolyl)androst-4,16-dien-3-one(4,L-39)is the most promising inhibitor of 17α-hydroxylase/C17,20-lyase(P45017α)and 5α-reductase(5α-R),and has potential uses in the treatment of prostate cancer and benign prostatic hypertrophy.Its synthesis has been improved with much higher yield in this paper.First,the Claisen condensate(2)was cyclized with hydroxylamine in ethanol to give pure 5′-isoxazole 3a,which could be oxidized directly by Swern oxidation and then isomerized in acid to give L-39(4).Second,2 was cyclized with hydroxylamine in anhydrous formic acid to give 3-formate(7),which was then oxidized directly by the modified Oppenauer oxidation to give 4-en-3-one(4).
