化学结构与药理活性课件.ppt

1、P=C生物相C水相P o/w=CwCox=lgPx-lg P HCHCHCH2CH3CH3CH3COOHOH3CCH3HOHOOOH3CCH3NRR NHNH2NHRNH2NHNOCOOHNHNF一个分子可能有多个官能团，因而具有酸和碱的双重性质。NOCOOHN+H2NFNOCOO-N+H2NF胃Ph(1.03.5)十二指肠(pH4)RH未解离 （水溶性）（脂溶性）细胞膜的结构壁磷壁酸膜磷壁酸HA +H2OA-+H3O+Ka =H3O+A-HA-lg Ka=-lgH3O+-lgA-HA-lgKa=pKa,-lg H3O+=pHp Ka=pH-lgA-HAA-HA=pKa-pHlgB +H2O

2、BH+OH-lg=pH-pKaBBH+三、药物的水溶性v（一）氢键药物v（二）解离v3.药物的溶解度v4.药物的分子量有效药物的分配系数在0.52之间SO2NH2NH2SO2NHNH2SNNC2H5氨苯磺胺 磺胺乙噻二唑pH=5 未解离76%pH=8 未解离0.3%v例如羧苯磺胺类化合物的肾脏相对清除率ClR与lgP有关：vlgClR-0.242(lgP)2-0.035lgP+0.578vn=9,r=0.98,s=0.16SO2NHOOCCH2CH2CH3CH2CH2CH3R +D RD k1k2k3EK=k1k2G=-RTInKOCRRN受体HHRN+N受体HH:NHOC:+_药物类型药物类

3、型亲和力亲和力复合物复合物内在活性激动剂k1k2+k3较大无活性k1k2-拮抗剂k1k2+k3=0部分激动剂k1k2+k3较小R +D RD k1k2k3EOOOHHOOHOOOHHOOHOHOOH己烯雌酚OHHO雌二醇考迈斯托醇金雀异黄素药效团学说立体因素对药效相的影响分为：NH CCH3CHONHCH2CH2CH3CH3丙胺卡因SCH2CHN(CH3)2CH3NClCHCH2CH2N(CH3)2氯苯那敏OCH2CHCH2NHCH(CH3)2OH普萘洛尔左旋体右旋体CH2HOHOCCH3COOHNH2L-甲基多巴CH2CHOC2H5NH(CH3)2CH3L-美沙酮CHCHCH2CH3CH3C

4、H3COOHD-布洛芬活性NHCH3O2NCOOCH(CH3)2CH3NN(+)钙拮抗剂(-)钙激动剂BAY K8644CCH2C6H5CHOCOCH2CH3C6H5(CH3)2NCH2NH3CHCH2N曲普立啶HOOH己烯雌酚ESC 氯普噻吨HCH2CH2N(CH3)2E：抗组胺药 H1受体 Z：抗精神病药多巴胺受体Cl神经递质组胺有不同构象v神经递质组胺可作用两种受体，呈现两种不同激动活性，以偏转构象作用于H1受体，以反式构象作用于H2受体。H1受体受体H2受体受体CNOFNe CHNHOHHF CH2NH2OH2 CH3NH3 CH4RCHOCH2CH2N(CH3)2R=H 苯海拉明R=

5、Cl,CH3,CH3OCH2NHOOCH3C2H5乙琥胺（吡咯环）NHNHOOC6H5C6H5苯妥英（咪唑环）ONHOOCH3CH3三甲双酮（f唑环）XNR2R3R1COOHOX=-N=萘啶酸X=-CH=喹诺酮类XCH2OCONH2CH2OCONH2CH3CH2CH2CH3X=C 甲丙氨酯X=Si 硅甲丙氨酯SNNHSHNNNHCH3CNCH3西咪替丁NSSHNNHCH3NO2(CH3)2N尼扎替丁NSSHNNNHCH3SO2NH2N法莫替丁H2NH2NOSHNNHCH3NO2(CH3)2N雷尼替丁NNClCH2OHX X IC50COOH 0.25molNKNNN 0.019mol氯沙坦HOOH己烯雌酚OHHO雌二醇OCH2CHCH2NHCH(CH3)2OHMR=n2-1n2+1MWdNNOCOOHC2H5C2H5NOR5R6R7R8R1COOHNNCH3NHNNOR5R6R7R8R1COOHNHNNNCH3NOR5R6R7R8R1COOHNOFC2H5COOHNHN