天然藥物化學第十一章天然藥物的開發(fā)課件

1、第十一章 天然藥物的研究開發(fā)芳香性：醌、苯丙素、黃酮非芳香性：糖、萜、甾體不含氮含氮: 生物堿天然藥物主要來源：生物堿，萜，皂苷一. 內(nèi)容總論各論提取分離結(jié)構(gòu)測定生物合成天然藥物R&D緒論THE CONTINUING NEED FOR DRUG DISCOVERYExpanding global populationBiodiversity is decreasingDrug Resistance is increasingNew diseases are emerging (e.g. SARS)BUT - the cost to market a new drug is increasing

2、 now at least $700 millionAND - the role of natural products as pharmaceuticals is well-establishedPharmaceutical companies are looking for enhanced chemical (structural) diversityNATURAL PRODUCTS AS PHARMACEUTICALSONeill and Lewis (1993) - over 50% of leading Compounds were nat. prod. based.Newman

3、et al. (2003) - between 1981 2002: 340 (39%) of the 868 New Chemical Entities (NCEs) were nat. prod. or nat. prod. based-J. Nat. Prod. 2003, 66, 1022. Over 80% of worlds population use plants as a primary health care source$4.2 Billion on phytotherapeuticals in U.S. in 1999中藥現(xiàn)代化基礎(chǔ)：文獻資料，民間用藥經(jīng)驗 手段：生物活

4、性測試（高通量篩選），提取分離技術(shù)對象：天然產(chǎn)物：陸地，海洋；動植物（中藥），微 生物，礦物內(nèi)容：分離，結(jié)構(gòu)測定（波譜技術(shù)結(jié)合化學方法）, 理化性質(zhì)，半合成，全合成，結(jié)構(gòu)改造（組合化學）目的：發(fā)現(xiàn)新的先導化合物或藥物 利用和改善藥物來源 創(chuàng)制新的藥物二. 學科 定義：基礎(chǔ) 手段 對象 內(nèi)容 目的 涉及學科治療的目標 尋找先導化合物 優(yōu)化先導化合物 研制侯選藥物 新藥1. “當歸蘆薈丸”(11味) 青黛 靛玉紅 合成 靛玉紅 (Indirubin)靛蘭 (Indigotin)治療慢性粒細胞白血病青蒿素氫化青蒿素還原青蒿素蒿甲醚還原青蒿素琥珀酸鈉Anticancer agentsR = H 喜樹堿(camptothecine)R = OH 10-羥基喜樹堿(hydroxycamptothecine)珙桐科植物喜樹(Camptotheca acuminata)治療多種惡性腫瘤:骨癌、肝癌、膀胱癌和白血病副作用: 骨髓抑制、嘔吐和腹瀉 水溶性差伊立替康(irinotecan)R1 =R3 = EtR2 = H拓撲替康(topotecan)R1 =