藥物化學十一章激素

112–––––3M1A11M1A112411134OOOOOOOHOONH5OOOOOOOHOONH5OOO6OOO6OOOOOO7–1935OO–1935OO–O8OO[[+OO9OO[[+OO9OOOOOO進入體內(nèi)后逐漸水解放出OOO進入體內(nèi)后逐漸水解放出OOO––二氫睪酮：Testosterone：△4–5a-還原二氫睪OHOOO17b-脫氫OOH4––二氫睪酮：Testosterone：△4–5a-還原二氫睪OHOOO17b-脫氫OOH4-雄烯二O17a-甲基衍生甲17a-甲基衍生甲睪OOOOO[ OOOOOOO[ OOOProgesterone及17a-Progesterone及17a-OOOOOOOOOOOOOO17a-黃體在研究皮質(zhì)激素生17a-黃體在研究皮質(zhì)激素生物合成過程中，發(fā)現(xiàn)17aOOORO己酸羥孕酮（17a-–油劑注射一次延效1O己酸羥孕酮（17a-–油劑注射一次延效1OOOROR=-R=-OOOOHOHHHOOOOHOHHHO3O6O3O617a-乙酰氧基黃體酮的6a–OOOOO17a-乙酰氧基黃體酮的6a–OOOOOOOOOOOOaaO6a-6a-66-6-6-6-6-6-OOOROOO（將17a乙炔基作為取代基（將17a乙炔基作為取代基–A環(huán)保持△4-3O炔諾17a位引入乙炔17a位引入乙炔基后，雄激素活性減弱–O1/10Testosterone––––1/10Testosterone––––OOOOOOOO OOOO OOOOOOOOO17a17aO–O–OHHHHO9O8HHHHO9O8(+)-Enantiomer↗↘O↗↘OOHHOOOOOH2,Li,OHHOOOOOH2,Li,OOKCOONONONONONONOON孕激（拮抗劑OOO黃體炔諾米非ON孕激（拮抗劑OOO黃體炔諾米非司NO雌激（拮抗劑己烯雌雌二RP+A-CnRRRBP甾體激素（P，孕激素）RP+A-CnRRRBP甾體激素（P，孕激素）N 9ON 9ON 9ON 9OOOOOOOOOONOOOOOONNOOOOOOOOOOOOOOONOOOOOONNOOOOOO如口服200mgOOO如口服200mgOOONN. . OOHN. OOONN. . OOHN. OOO移至鄰位或間位，增加口服活NO引入-CH3、-CH2OH抗劑轉(zhuǎn)變?yōu)榧?1OOO2OOOOOOOOOHOOOOOOOOOOOOOHOOOOOO3OOOOO4OOOOO4OOO5OOO5–OO6–OO6000化合皮質(zhì)肝糖元沉0鈉潴8OOOOOOOOOOO5b-孕甾5b-孕甾烷甾OOOOO△4，53OOOOO++ HHOOOOO△4，53OOOOO++ HH化–O1化–O1O3--O---O---O-COCH2CH2COO--在OO在OO變–OOOO變–OOOOOOFOOOFOOOO 19OOO 19F3O4OOFOOOFO21-酯20Ob11羥Oa17羥21-酯20Ob11羥Oa17羥Fa16甲Oa9C-16aOOOOC-16aOOOOOOOHFOOOOHFOOODMF,OOOOOOFFOOOOFOOODMF,OOOOOOFFOOOOFOOBDC-21OHOOBDC-21OHOCAO–OOFOFHO–OOFOFHOOOHOCOOHOCAOOOOH-HOOOOOOH-HOOOOC-21OC-21OOOOFOOOOFOa，bOPOPOOFFOa，bOPOPOOFFOO糖皮質(zhì)激素結(jié)構(gòu)修飾（續(xù)糖皮質(zhì)激素結(jié)構(gòu)修飾（續(xù)抗炎活性和糖元沉積活性比皮質(zhì)醇大10OOO抗炎活性和糖元沉積活性比皮質(zhì)醇大10OOOFO患腎上腺癌病人的尿中發(fā)現(xiàn)–患腎上腺癌病人的尿中發(fā)現(xiàn)–Hydrocortisone的16a羥基代謝產(chǎn)它的糖皮質(zhì)激素活性依舊保留，而鈉潴留的發(fā)現(xiàn)C-16甲基的引入使17a羥基及發(fā)現(xiàn)C-16甲基的引入使17a羥基及C-20OOOHFO–醋酸膚輕松（FluocinonidOOOOOFOF–醋酸膚輕松（FluocinonidOOOO