苯二氮卓类课件.ppt

1、NNR4123456791/2/3/4/5/6/ABCR1O8R2R3NNClNHCH3O氯氮卓NNClCH3O地西泮NR1NOR3R1=H, R2=H, R3=NO2, 硝西泮R1=H, R2=Cl, R3=NO2,氯硝西泮R1=(CH2)2N(C2H5)2, R2=F, R3=Cl 氟西泮R2NHNOClOHR1R1 = H 奥沙西泮R1 = Cl 劳拉西泮NNSClFCH2CF3夸西泮NNClFNH3C咪达唑伦NHNOBrOF卤f唑仑SNNNNCH3 依替唑伦ClCH3NNNClR2NR1R1=H R2=H 艾司唑伦R1=CH3 R2=H 阿普唑伦R1=CH3 R2=Cl 三唑伦NNCl

2、CH3O地西泮NNClCH3ONNClCH3OHHHHabNNClCH3ONNClCH3OHCH3CH3HSR稳定,活性强NNOClCH3diazepanNHNOClOH4hydroxydesoxydemoxepamNHNOClnordazepamNHNOClOH9-hydroxydesoxydemoxepamNHNOClOHoxazepamNNCH3OCl（CH3)2SO4CH3C6H5Fe , HClC2H5OHClON3-苯-5-氯嗯呢ClON+CH3ClNHCH3OClCH2COClC6H12ClNCOCH2ClOCH3NNCH3OCl(CH2)6N4.HClCH3OHIIINHNOC

3、l2) NaNO2, HCl3)-萘酚ClNONHO1)H+NNCH3OClH+OH-ClNHCH3O+ H2NCH2COOH2-甲氨基-5-氯-二苯甲酮ONCH3OClNH2H+NNHCH3ClCOOHNHNOR2 R2=H, R3=NO2, 硝西泮 R2=Cl, R3=NO2,氯硝西泮R1NNNClR2NR1R1=H R2=H 艾司唑伦R1=CH3 R2=H 阿普唑伦R1=CH3 R2=Cl 三唑伦NNClFNH3C咪达唑伦NNCH3OClNH2NCH3OClOClNOCH3NHNH2OONH2Ro7355肽酶前药Ro7355NNNClNHNNNClNHONNClNHH+NH3+NNCH3

4、H3CN(CH3)2ONNNONN CH3NClOCOHNNHOOO124563R1R2HNNHOOONNHOOHONNOHOHONNOHOHHO巴比妥酸单内酰亚胺双内酰亚胺三内酰亚胺124563HNNHOOO124563R1R2R3NNHOXO124563R1R2名称名称pKa分子态药物分子态药物离子态药物离子态药物巴比妥酸巴比妥酸4.120.0599.955-苯基巴比妥苯基巴比妥酸酸3.750.0299.98苯巴比妥苯巴比妥7.2943.7056.30海索比妥海索比妥8.4090.919.09HNNHOOO124563R1R2NHNHC6H5C2H5OOONHNHC2H5OOOHONHNH

5、C2H5OOONHNHC2H5OOOOHNHNHR1R2OOOCHCNHCNH2R1R2OOCR1R2CONH2CONH2NHNHC2H5OSOH3CNHNHC2H5OOOH3CNNHH3COOOCH3NHNHH3COOONHNHR1R2OO(S)OH2CCOOC2H5COOC2H5R1XC2H5ONa CHCOOC2H5COOC2H5R1R2XC2H5ONa CCOOC2H5COOC2H5R1R2NHNHR1R2OO(S)OH2NCNH2C2H5ONaO(S)IIIIIINNHOOONaR1R2CHCONHCONH2R1R2+ NaHCO3CHCOONa + NH3R1R2室温NHNHC6H

6、5C2H5OOONHNHC6H5C2H5OOOC6H5CH2COOC2H5COOC2H5COOC2H5C2H5ONa CHCOCOOC2H5COOC2H5C6H5CO CHCOOC2H5COOC2H5C6H5C2H5BrC2H5ONa CCOOC2H5COOC2H5C6H5C2H5H2NCONH2C2H5ONaHClNHNHC6H5C2H5OOOIIIIIICHOHOHCl3C 水合氯醛安全的催眠、抗惊厥药代谢CH2OHCl3CCH2OPO3H2Cl3C三氯乙醇膦酸酯CHNHCOOC2H5Cl3C氨基甲酸乙酯水合氯醛OH三氯乙醇活性前药CCH2OCONH2CH2OCONH2H3CCH3CH2C

7、H2NNCH3OH3CNHNHC6H5C2H5OO扑米酮（扑痫酮） NHNHC6H5C2H5OOO苯巴比妥NHNHC6H5C6H5OO苯妥英ONH3CH3COOCH3 三甲双酮 毒性大（f唑烷双酮类） 失神性小发作NHC2H5H3COO 乙琥胺（丁二酰亚胺类） 癫痫小发作NHNHC6H5C2H5OO5-乙基-5-苯基-乙内酰脲 毒性大生物电子等排v抑制大脑皮层运动中枢，提高惊厥的阈值。NHNC6H5C6H5OONa135NHNC6H5C6H5OONaNHCONH2COOHC6H5C6H5NH2COOHC6H5C6H5NaOH+ NH3NHNC6H5C6H5OONaNHNHC6H5OOHONHN

8、HC6H5OOGluONHCONH2COOHC6H5C6H5+NH2COOHC6H5C6H5NNClCH3OONCONH2NCONH2NCONH2ONCONH2OHOH环氧化物酶卡马西平CYP450CHCORCH3CH2CH2CH3CH2CH2R = HR=ONaR = NH2丙戊酸丙戊酸钠丙戊酰胺H2NOHOv作用机理可能是通过抑制脑内兴奋性介质谷氨酸和天门冬氨酸的过量释放，产生抗癫痫作用。NNNClClNH2纹状体中NSCH2CH2CH2NRRRNSCH2CHN(CH3)2CH3异丙嗪NSCH2CH2CH2N(CH3)2Cl12345678910氯丙嗪 NSCH2CH2CH2R1R2NNC

9、H2CH2OHNNCH3NNCH2CH2OHClCF3CF3 奋乃静氟奋乃静 三氟拉嗪NSCH2CH2CH2CF3NNCH2CH2OCOC6H13氟奋乃静庚酸酯23周注射一次 R1 R2N(CH3)2 COCH3 乙乙酰酰丙丙嗪嗪N(CH3)2 CF3 三三氟氟丙丙嗪嗪1045013NHRSI2NHSR+NHSR少量NaNH2Cl(CH2)3NR2/NSCH2CH2CH2NR2/ClNSCH2CH2CH2NRRRNSCH2CH2CH2N(CH3)2.HClClNSCH2CH2CH2ClNNCH2CH2OHXRCl -N(CH3)2 氯普噻吨CF3NNCH2CH2OH氟哌噻吨Cl 珠氯噻醇NNC

10、H2CH2OHNSCH2CH2CH2RXSCHCH2CH2RXNCOOC2H5H3C哌替啶FCO(CH3)3NR1R2123456R1 OH OHR2ClCF3氟哌啶醇三氟哌多NNNOFCO(CH2)3氟哌利多广泛用于治疗急、慢性精神分裂症和躁狂症RCO(CH2)3NR1R2急、慢性FCO(CH2)3NOHCl234561FCO(CH2)3NOHClFCO(CH2)2CHOFCO(CH2)2COOHFCH(CH2)3NOHClOHFCH(CH2)2CHOOHFCH(CH2)2COOHOHFCO(CH3)3NR1R2123456FCH(CH2)3NR2R1FR1 HNNHOR2匹莫齐特Cl五氟利

11、多OHCF3NHNC6H5O 氟司必林一天一次 两周一次 一周一次H2NO2SCONHCH2OCH3NC2H5NNHNNCH3Cl二苯并氧氮卓类，和氯丙嗪、氟哌啶醇一样能阻断纹状体多巴胺受体，因而临床应用、疗效及不良反应相似，也可导致NONNCH3ClNNOONNNNSCH2CH2CH2NRRRN(CH2)3NRRRN(CH2)3NRRR 丙咪嗪类抗抑郁作用增强N(CH2)3NRCH3R CH3 丙咪嗪Cl H 地昔帕明作用快，副作用小NONHNClNSCH2CH2CH2NRRRN(CH2)3NRRR丙咪嗪SCH2CH2CH2RXCH(CH2)2NRCH3R=CH3 阿米替林 R=H 去甲替林拼合原理CH(CH2)2N(CH3)2.HCl1234567891011ab cdOCHCH2CH2NHCH3F3CNCONHNH2C C l lC C O O C C H HN NH HC C H H2 2C C ( (C CH H3 3) )3 3C C H H3 3