《非甾类抗炎药》PPT课件

A Free sample background from Slide 1 A Free sample background from Slide 2 A Free sample background from Slide 3 O COOHCH3OHO COOHCH3OHOHO COOHCH3OHHOHO COOHCH3 OHHOOPGH2PGE2 PGF2 PGD2PG endoperoxide reductasePG endoperoxide E isomerase glutathione-S-transferase PG peroxidase A Free sample background from Slide 4 A Free sample background from Slide 5 A Free sample background from Slide 6 PGH2O COOHCH3OHO COOHCH3OHOHOHO TXA2 TXB2 COOHCH3 OH HOHO O CH3OHHOO COOHPGI2 6-keto PGF1 prostacyclinsynthetasethromboxanesynthetase COOH CH3OHOO A Free sample background from Slide 7 A Free sample background from Slide 8 A Free sample background from Slide 9 A Free sample background from Slide 10 COOHCH3AA Cell membrane phospholipidsPhospholipase A2 12-HPETE 12-HETECOOHCH3 OOH 5-HPETE 12-lipoxygenase 5-lipoxygenase LTA synthetase CH3COOHOH COOHCH3OOH A Free sample background from Slide 11 dipeptidase glutathione-Stransferase COOHC5H11 OHS COOHNHH2N OHOOC COOHC5H11 OHSH2N COOH COOHC5H11 OHS NH COOHOH2N LTA hydrolase COOHC5H11 OHS NH COOHONHH2N OHOOC LTF4 LTE4 LTD4 LTC4LTB4 LTA4COOHCH3OHOH COOHCH3O -glutamyl transpeptidase -glutamyltranspeptidase A Free sample background from Slide 12 A Free sample background from Slide 13 A Free sample background from Slide 14 A Free sample background from Slide 15 A Free sample background from Slide 16 A Free sample background from Slide 17 CH3NH O H3C O CH3NH OAcetanilide Phenacetin A Free sample background from Slide 18N-(4-羟基苯基)乙酰胺N-(4-Hydroxyphenyl)acetamide醋氨酚（Acetaminophen）扑热息痛 CH3NH O HO A Free sample background from Slide 19 A Free sample background from Slide 20 Glu N CH3HO OH N CH3HO OOH N CH3O OH N CH3O OSHOO O H N CH3OH N CH3O OH3C H NH2OH3C Glucuronide sulfatephenacetin Acetanilide hepatotoxicmethmoglobinemia,hemolytic anemia A Free sample background from Slide 21 glutathione N CH3O O N CH3HO Oglutathine H N-acetylimidoquinone reactive metabolite hepaticproteins N CH3HO OHhepaticproteinsN CH3HO OSHO OHN CH3O HN-acetylcystein hepatic necrosisrenal failure rena l e xcretion as mercapturic acid o r cysteine conjuga tes A Free sample background from Slide 22 A Free sample background from Slide 23 A Free sample background from Slide 24 COOHOH COOHO CH 3 CONH2OHO A Free sample background from Slide 25 A Free sample background from Slide 26OHOOCOCH3 COONHCOCH3FFOHOHOOCOOH在水杨酸的5-位引入芳香环，可以增加其抗炎活性，例如，引入二氟苯基得到二氟尼柳（Diflunisal）,其抗炎和镇痛活性均比阿司匹林强4倍，体内的维持时间长达812h，胃肠道的刺激性小，可用于关节炎，手术后或癌症引发的疼痛的治疗。 A Free sample background from Slide 27 A Free sample background from Slide 28 COO-OCOCH3 COO- OH. (CH 3)3N+CH2CH2OH COO- OCOCH3. H3N+CH(CH2)4N+H32AlOH COO-阿司匹林 Aspirin O OHO CH3 O A Free sample background from Slide 29 OHOH O + H 3C OO CH3O H2SO47075 O OH O O CH3 A Free sample background from Slide 30 COOHOCOCH3+ (CH3CO)2O OCOCH3O OCOCH3O O O CH3 OO CH 3O O O A Free sample background from Slide 31 OHOH + Fe3+O OOHO Fe3+ OHOHO OHOHOHO OHOO O OHOHOHO HO OHO O OHO OHO 或 HO O-O O+ OHO O黄色 蓝至黑色 A Free sample background from Slide 32 O OHO CH3O OHOH O COOHO Glu OO GluOH NHCH2COOHOOH OHOHHO OHO OHOOHOH NHCH2COOHOOHHOOHOOHHO UDP-葡萄糖醛酸转移酶 UDP-葡萄糖醛酸转移酶甘氨酸N- 酰基转移酶 甘氨酸N-酰基转移酶龙胆酸SA A Free sample background from Slide 33 A Free sample background from Slide 34 A Free sample background from Slide 35 A Free sample background from Slide 36 NO N CH3CH3 NH3C NN CH3CH3 CH3O N NN CH3CH3 CH3ONaO3S NO N CH3CH3CH 3H3C AntipyrineAminopyrine Metamizole SodiumIsopropylantipyrine A Free sample background from Slide 37 A Free sample background from Slide 38 A Free sample background from Slide 39 NNH3C O O NNH3C O O OH NNH3C O OO A Free sample background from Slide 40 NHNHR O O H NHNHR O O_ + H+ NHNHR O O H _ A Free sample background from Slide 41 NNH3C O O NNH3C O OCOH2COHOOC NNNH3C O OH3C CH3 A Free sample background from Slide 42 A Free sample background from Slide 43 A Free sample background from Slide 44 X NHOH O R1R2R3 A Free sample background from Slide 45 A Free sample background from Slide 46 A Free sample background from Slide 47 A Free sample background from Slide 48 A Free sample background from Slide 49 NHHO NH2 NHHO NH2COOH5-羟色胺 色氨酸 NH3CO OHO CH3 O Cl吲哚美辛 lndomethacin A Free sample background from Slide 50 A Free sample background from Slide 51 F OHOCH3 SCH3O F OHOCH3 H3CSF OHOCH 2OH SCH3O F OGluOCH2OH SCH3O F OHOCH3 SH3CO F OGluOCH3 SH3CO OH OH O O 舒林酸 活性代谢物 砜代谢物 A Free sample background from Slide 52 NH3CO OHO CH3O Cl2-甲基-1-(4-氯苯甲酰基)-5-甲氧基-1H-吲哚-3-乙酸；1-(4-Chlorobenzoyl) -5-methoxy-2-methyl-1H-indole-3-acitic acid A Free sample background from Slide 53 1,NaNO2,HCl2,Na2SO3NH2H3CO NH3CO N SO3NaZn / HCl NHNHSO3NaH3CO Cl COCl NH3CO C OCl HN SO3Na NH3CO O Cl NH220% NaOH NH3CO OHOCH3OClH3C OHOO HAc A Free sample background from Slide 54 A Free sample background from Slide 55 N H3CO OHO CH3 O A Free sample background from Slide 56 A Free sample background from Slide 57 NH3C O ONaOCH3 Tolmetin Sodium依托度酸（Etodolac）含有三环结构，其镇痛消炎作用与Aspirin相当。它可以在炎症部位选择性的抑制前列腺素的生物合成，对胃和肾脏的前列腺素的生成没有影响，其副作用发生率较低。适用于类风湿性关节炎以及抑制轻度至中度疼痛。 N O OHCH3 OCH3HEtodolac A Free sample background from Slide 58 Cl HN ONaCl O2-( 2,6-二氯苯基 ) 氨基 苯乙酸钠；2-(2,6-Dichlorophenyl)amino benzeneacetic acid sodium salt，又名双氯灭痛。 A Free sample background from Slide 59 A Free sample background from Slide 60 Cl OH Cl NH2 NHCl Cl ClCH2COCl N ClCl O NaOH NH ClCl ONaO A Free sample background from Slide 61 Cl OClHO HN OH HN ClCl OOH HN ClCl OOH HO HNClCl OOHOH HNClCl OOHHO OH A Free sample background from Slide 62 CH3O OH3C A Free sample background from Slide 63 OHO O A Free sample background from Slide 64 OHO O OHOOH OHO OHOOH OHOO OHO A Free sample background from Slide 65 A Free sample background from Slide 66 OH OH3C CH3 OH OH3C CH3 CH3 A Free sample background from Slide 67名称 结构式 抑制鹿角菜水肿 （Indomethacin = 1） pKa 布洛芬 Ibuprofen H3C CH3O OHCH3 1/10 4.4 氟比洛芬 Flurbiprofen OHF CH3O 5 4.2 非诺洛芬 Fenoprofen OHCH3OO 1/10 4.5 酮洛芬 Ketoprofen OHCH3OO 1.5 4.55 A Free sample background from Slide 68萘普生 Naproxen OHCH3 OOH3C 1 4.39 噻洛芬酸 Tiaprofenic Acid S OHCH3OO - 3.0 吡洛芬 Pirprofen N OHCH3OCl 1 - 吲哚洛芬 Indoprofen N OHCH3OO 2 - 洛索洛芬钠 Loxoprofen Sodium ONaCH3OO - - A Free sample background from Slide 69 A Free sample background from Slide 70 A Free sample background from Slide 71 A Free sample background from Slide 72 OH OH3C CH3 CH32-(4-异丁基苯基)丙酸（RS）-2-(4-Isobutylphenyl)propionic acid A Free sample background from Slide 73 H3C CH3 CH3 H3C O CH3 H3C CH3 CH3CH3COCl ClCH2COOC2H5EtONa O OC2H5 O AlCl3 O H3C CH3 H CH3 O H3C CH3 OH CH31, NaOH2, HCl 1, AgNO3, OH-2, H+ A Free sample background from Slide 74 OH H3C CH3 CH3 O OH HOOC CH3 CH3 O OH HOH2C CH3 CH3 O OH H3C CH3 CH3 O OH H3C CH3 CH3 O OH HOOC CH3 O (+ )布洛芬 OH OH A Free sample background from Slide 75 A Free sample background from Slide 76 A Free sample background from Slide 77 S N CH3 NH N OOH O O S N CH3 NH OOH O O N S吡罗昔康舒多昔康 S N CH3 NH OOH O O S N CH3美洛昔康 A Free sample background from Slide 78 NH S N CH3O O OH O ON CH3 NH S N CH3O O OH O S N S N CH3 NH N OO O O O O O CH3H3C噻吩昔康 伊索昔康 安吡昔康 A Free sample background from Slide 79 S N CH3 N H N OOH O O2-甲基-4-羟基-N-(2-吡啶基)-2H-1,2-苯并噻嗪-3-甲酰胺1,1-二氧化物；4-Hydroxy-2-methyl-N-2-pyridinyl-2H-1,2-benzothiazine-3-carboxamide-1,1- dioxide。又名炎痛喜康。 A Free sample background from Slide 80 S N CH3 NH N OOH O O S N CH3NH N OO O O S N CH3N NH OO O O - - - -A B A Free sample background from Slide 81 SN Na O O O + Cl O CH3 O DMF SN O O O O CH3 O C2H5ONa S NH OH O O O O CH3 S N OH O O O O CH3 CH3 二甲苯 N NH2 S N CH3 NH N OOH O O (CH3)2SO4 NaOH A Free sample background from Slide 82 S N CH3 NH N OOH O O S N CH3NH N OOH O O S N CH3NH N OOH O O OH S N CH3O O NN O S N CH3 OH OOH O O S N CH3 O O O S NH O O O 吡罗昔康 人体内主要代谢物 狗中主要代谢物 少量 HO A Free sample background from Slide 83 NN FF F SH2NO O化学名4-5-（4-甲基苯基）-3-三氟甲基-1H-吡咯-1-基苯磺酰胺（4-5-（4-5-(4-Methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-ylbenzenesulfonamide）。别名celecoxib A Free sample background from Slide 84 A Free sample background from Slide 85 120位精氨酸 亚铁红素 120位精氨酸 憎水区域 憎水区域袋状亲水区 385位酪氨酸 COX-1 COX-2 + + 385位酪氨酸 A Free sample background from Slide 86 120位精氨酸 385位酪氨酸 120位精氨酸 385位酪氨酸 COX-1 COX-2 + +磺酰胺侧链的氮与513位精氨酸和90位组氨酸形成氢键 A Free sample background from Slide 87 -SBr FS NH2OO O S OOODup607 罗非昔布Rofecoxib根据构效关系的研究，发现分子中的两个苯核较为重要，特别是在苯核的4位以磺酰胺基或甲磺酰基取代活性最强，若其它取代基时，其活性较低。在另一个苯核的对位应有取代基如甲基、甲氧基、氯、溴、氟。但以氟取代物活性最强。在分子中易变部位为其五元环。五元环可以为噻吩、噻唑、吡咯、噁唑、咪唑、噁唑酮、环戊烯等，当在五元环上存在与其共平面的取代基时，活性较强，尤其是三氟甲基，如罗非西克（Rofecoxib）。 A Free sample background from Slide 88 NN FFFSH2NO O与523位的缬氨酸结合 4-位以氟取代最佳此部分变化最大，多数为五元环，以平面结构为多，且在环上连有一吸电基团 A Free sample background from Slide 89 Celebrex的合成 NN FFFSH2NO OO + FFF O O NaOCH3CH3OH OFFFHO NH2SH2NO O NH2 . HClEtOH A Free sample background from Slide 90 Celebrex 的代谢 NN FFFSH2NO O OHO NN FFFSH2NO O OH NN FFFSH2NO O OGlu