化学名2-甲基.ppt

Chapter 3Analgetics and nonsteriodal antiinflammatory agents;3.1 Salicylic Acid ---aspirin and aspirinlike drugs;Aspirin;;It has been known that aspirin, and the aspirinlike drugs, have several pharmacological properties: antipyresis, analgesia, and antiinflammatory characteristics.;Mechanism of drug action: Inhibitor of cyclooxygenase, Relieve pain by blocking the biosynthesis of prostaglandins(PGs) ;History：;In 1875, salicylic acid sodium was used as antipyretics as pain relieving agent. In 1866, salicylate ester was used in clinics. In 1853, aspirin was synthesized，in 1899 it was used as a medicine。;阴离子是活性的必要结构，如果酸性降低，虽保持其镇痛作用，但抗炎活性减少。置换羟基成酚羟基可以影响疗效和毒性。羧基与羟基的位置若从邻位移到间位或对位，可使活性消失。;Metabolic reaction: ;Metabolism of aspirin：;Physicochemical properties: ;;identification：;synthesis：;Side reaction：;;Paracetamol; 白色结晶或结晶性粉末，无臭，味微苦。在热水或乙醇中易溶，在丙酮中溶解，在水中略溶。Mp.168~172℃;phenylacetamide was discovered in1886. –具很强的解热镇痛作用，称退热冰，并在临床上使用。 –其毒性太大，可导致出现高铁血红蛋白和黄疸 –在临床上已不用 Phenacetin was discovered with slight toxin and better activity. Phenacetin was synthesized in 1887. –对头痛、发热、风湿痛、神经痛及痛经等效果显著， –曾广泛用于临床.;Phenacetin对肾有持续性的毒性并可导致胃癌及对视网膜毒性，被各国陆续废弃使用。 Paracetamol was introduced as a antipyretic with very good activity in 1893 。 –临床上用于发热、头痛、风湿痛神经痛及痛经等，毒性低于Phenacetin。;对硝基苯酚经还原得对氨基酚，再经醋酸酰化后得到本品。;metabolism; Inflammation and its symptom: The coexistence of the phenomena, redness and heat, with swelling and pain, the ordinary symptoms of inflammation, may, therefore, be considered as sufficient evidence of the presence of the inflammatory condition.是机体对感染的一种防御机制，主要表现为红肿，疼痛等，引起的疾病有:风湿、类风湿性关节炎、风湿热、骨关节炎、红斑狼疮和强直性脊椎炎等。 苯胺之外，解热镇痛药具有抗炎作用，但长期和大量使用有肠道反应，对凝血或造血系统有严重的不良反应。;3.3 Pyrazolidones;;Oxyphenbutazone;3，5-吡唑烷二酮类药物的抗炎作用与化合物的酸性有密切关系;SAR of Phenybutazone;Metabolism of oxyphenbutazone;;3.4 arylakanoic acids: Aryl acetic acids and Aryl propanoic acids;Indomethacin; 5-羟色胺（Serotonin，5HT）为炎症的化学致痛物质，Serotonin的体内生物来源与色氨酸（Tryptophan）有关，发现风湿患者体内Tryptophan代谢水平较高。; discovered indomethacin f