非甾体抗炎药的作用机制

第一节非甾体抗炎药的作用机制一、花生四烯酸的代谢花生四烯酸(Arachidonicacid,AA)5,8,11,14-二十碳四烯酸环氧合酶(Cycloxygenase,COX)途径代谢脂氧合酶(Lipoxygenase)途径代谢20，非甾体抗炎药环氧合酶有两种不同的形式COX-1生理条件下保持相对恒定的浓度,调节正常组织细胞的生理活动COX-2能被诱导而高度表达,产生红肿、水肿、疼痛和发热抗炎药的作用靶点磷脂磷脂酶甾体抗炎药花生四烯酸环氧合酶抑制剂环氧合酶脂氧合酶脂氧合酶抑制剂非甾体抗炎药非甾体抗炎药前列腺素类白三烯类抑制抑制抑制第二节传统的非甾体抗炎药水杨酸类吡唑酮类芳基烷酸类邻氨基苯甲酸类1,2-苯并噻嗪类一、水杨酸类OHCOOHOCOCH3COOHOHFFCOOH水杨酸Salicylicacid乙酰水杨酸(阿司匹林)Aspirin二氟尼柳Diflunisal二、吡唑酮类分为5-吡唑酮和3,5-吡唑烷二酮(一)5-吡唑酮类NNCH3CH3RO通式：先导化合物：安替比林(Antipyrine)NNCH3CH3RO代表药物：NNCH3CH3NOCH2SO3NaCH3NNCH3CH3RO安乃近Analgin异丙基安替比林Isopropylantipyrine(二)3,5-吡唑烷二酮类NNOOOCH3OCOOHNNOOCH3CH3OOCH3NNNCH3NCH3CH3琥布宗Suxibuzone非普拉宗Feprazone阿扎丙宗Azapropazone三、芳基烷酸类(一)芳基乙酸类NMeOCH3CH2COOHOClHSCH3CH2COOHFOH3C吲哚美辛Indomethacin舒林酸SulindacNHClClCH2COONa双氯芬酸钠DiclofenacsodiumNHOCH3COOHC2H5CH3OMeOOCOOH依托度酸Etodolac萘丁美酮Nabumetone芬布芬Fenbufen(二)芳基丙酸类COOHCH3CH3H3C羧基部分芳香基团疏水基团布洛芬CH3COOHO酮洛芬NCH3COOHCl吡洛芬芳基丙酸类抗炎药的结构代表药物CH3CH3CH3COOHCH3COOHMeO萘普生Naproxen氟比洛芬Flurbiprofen布洛芬IbuprofenFCH3COOH萘普生的合成MeOCH3CH2COClAlCl3MeOC2H5OCuBr2MeOOCH3BrOOMeOCH3BrCH3CH3CH3CH3OHOHTsOH,PhCH3Zn(OAc)2CH3MeOCOONaCH3MeOCOOHCH3MeOCOOH(1)(2)OH-H+ZnO或拆分四、邻氨基苯甲酸类(灭酸类)药物名称XR1R2R3甲芬那酸MefenamicacidCHCH3CH3H甲氯芬酸MeclofenamicacidCHClCH3Cl氟芬那酸FlufenamicacidCHHCF3H氯芬那酸ChlofenamicacidCHHClH氯尼辛ClonixinNCH3ClH氟尼辛FlunixinNCH3FHXNHRRRCOOH12312五、1,2-苯并噻嗪类(昔康类，Oxicams)药物名称化学结构药物名称化学结构吡罗昔康Piroxicam舒多昔康Sudoxicam美洛昔康Meloxicam替诺昔康TenoxicamSNOHCH3OONHONSNOHCH3OONHOSNSNOHCH3OONHOSNCH3SNOHCH3OONHONS辛诺昔康Cinnoxicam氯诺昔康Lornoxicam安吡昔康AmpiroxicamSNOCH3OONHONOPhSNOHCH3OONHONSClSNOCH3OONHONOCH3COOC2H5美洛昔康的合成SNNaOOOClCH2COOCH3DMFSNOOOCH2COOCH3CH3ONa(CH3)2SO4NaOHSNOHCH3OOOOCH3SNHOHOOOOCH3SNOHCH3OONHOSNCH3CH3OHCH3CHOBr(NH2)2CSSNNH2CH3第三节选择性环氧合酶-2抑制剂二苯基取代环类甲磺酰苯胺类二叔丁基取代苯酚类二芳基取代环类FSCH3OOSCH3OOFFOSBrFSCH3OOSC-57666L-776967DuP-697NNFFFSONH2OCH3OSCH3OOONNClCH3SCH3OO塞利昔布Celecoxib罗非昔布Rofecoxib依托昔布EtoricoxibNOSNH2OOCH3NOSNOOCH3OCH3Na+－伐地昔布Valdcoxib帕瑞昔布Parecoxib甲磺酰苯胺类NHOSCH3OONO2NHSCH3OOONHCHOOONHOSCH3OOOFFNHSSCH3OOOFF尼美舒利NimesulideT614CGP-28238L-745337二叔丁基取代苯酚类NOOCH3OHCH3CH3CH3CH3CH3CH3OHCH3CH3CH3CH3CH3CH3SNONOCH3OHCH3CH3CH3CH3CH3CH3SNNSCH3BF-389PD-138387PD-164387塞利昔布的合成CH3CH3OCF3CO2C2H5CH3ONa/Et2OCH3OCF3ONHNH2SNH2OOEtOHNNFFFSONH2OCH3.HCl