1、P =C生物相C水相P o/w =CwCox = lgPx -lg P HCHCHCH2CH3CH3CH3COOHOH3CCH3HOHOOOH3CCH3NRR NHNH2NHRNH2NHNOCOOHNHNF一個(gè)分子可能有多個(gè)官能團(tuán)，因而具有酸和堿的雙重性質(zhì)。NOCOOHN+H2NFNOCOO-N+H2NF胃Ph(1.03.5)十二指腸( pH4)RH未解離 （ 水溶性） （脂溶性）細(xì)胞膜的結(jié)構(gòu)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 - lg

2、A-HAA-HA= pKa -pHlgB + H2O BH+ + OH-lg= pH - pKaBBH+三、藥物的水溶性v（一）氫鍵藥物v（二）解離v3. 藥物的溶解度v4. 藥物的分子量有效藥物的分配系數(shù)在0.52之間SO2NH2NH2SO2NHNH2SNNC2H5氨苯磺胺 磺胺乙噻二唑pH = 5 未解離76%pH = 8 未解離0.3%v例如羧苯磺胺類化合物的腎臟相對(duì)清除率ClR與lgP有關(guān)：vlgClR-0.242(lgP)2-0.035lgP+0.578vn=9, r=0.98, s=0.16SO2NHOOCCH2CH2CH3CH2CH2CH3R + D RD k1k2k3EK =k

3、1k2G = - RTInKOCRRN受體HHRN+N受體HH:NHOC:+_藥物類型藥物類型親和力親和力復(fù)合物復(fù)合物內(nèi)在活性激動(dòng)劑k1k2+k3較大無(wú)活性k1k2-拮抗劑k1k2+k3 = 0部分激動(dòng)劑k1k2+k3較小R + D RD k1k2k3EOOOHHOOHOOOHHOOHOHOOH己烯雌酚OHHO雌二醇考邁斯托醇金雀異黃素藥效團(tuán)學(xué)說(shuō)立體因素對(duì)藥效相的影響分為：NH CCH3CHONHCH2CH2CH3CH3丙胺卡因SCH2CHN(CH3)2CH3NClCHCH2CH2N(CH3)2氯苯那敏OCH2CHCH2NHCH(CH3)2OH普萘洛爾左旋體右旋體CH2HOHOCCH3COOH

4、NH2L-甲基多巴CH2CHOC2H5NH(CH3)2CH3L-美沙酮CHCHCH2CH3CH3CH3COOHD-布洛芬活性NHCH3O2NCOOCH(CH3)2CH3NN(+) 鈣拮抗劑(-) 鈣激動(dòng)劑BAY K8644CCH2C6H5CHOCOCH2CH3C6H5(CH3)2NCH2NH3CHCH2N曲普立啶HOOH己烯雌酚ESC 氯普噻噸HCH2CH2N(CH3)2E： 抗組胺藥 H1受體 Z：抗精神病藥多巴胺受體Cl神經(jīng)遞質(zhì)組胺有不同構(gòu)象v神經(jīng)遞質(zhì)組胺可作用兩種受體，呈現(xiàn)兩種不同激動(dòng)活性，以偏轉(zhuǎn)構(gòu)象作用于H1受體，以反式構(gòu)象作用于H2受體。H1受體受體H2受體受體CNOFNe CHNH

5、OHHF CH2NH2OH2 CH3NH3 CH4RCHOCH2CH2N(CH3)2R = H 苯海拉明R = Cl, CH3, CH3OCH2NHOOCH3C2H5乙琥胺（吡咯環(huán)）NHNHOOC6H5C6H5苯妥英（咪唑環(huán)）ONHOOCH3CH3三甲雙酮（f唑環(huán)）XNR2R3R1COOHOX = -N= 萘啶酸X = -CH= 喹諾酮類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+1MWdNNOCOOHC