{"title":"5-(1,4-二氢吡啶基)-四唑-2-乙酸、酯和酰胺的合成及其抗炎活性","authors":"P Kumar, E E Knaus","doi":"","DOIUrl":null,"url":null,"abstract":"<p><p>Thirteen 5-[3-(1,4-dihydropyridyl)]-2H-tetrazol-2-acetic acids (18-30), seventeen esters (4-17, 32, 35, 41) and eight amides (31, 32-34, 36-40) were synthesized in order to investigate the effect of alpha-substituents (R1 = H, Me) and 1,4-dihydropyridyl substituents (R2 = aryl, alkyl; R3 = phenoxy, methoxy or amino) on anti-inflammatory activity. The effects of the R1, R2 or R3-substituents were variable but highly interdependent. The relative order of anti-inflammatory potency was generally acid greater than amide and ester. Methyl 2-methyl-2-(5-[3-(4-phenyl-1-carbamoyl-1,4-dihydropyridyl)]-2H- tetrazol-2-yl) acetate (35) was the most effective anti-inflammatory agent in the group, reducing inflammation 96% at 5 hr after a 50 mg/kg po dose, relative to ibuprofen's 52% inhibition at 5 hr after a 100 mg/kg po dose.</p>","PeriodicalId":11271,"journal":{"name":"Drug design and delivery","volume":"7 4","pages":"287-94"},"PeriodicalIF":0.0000,"publicationDate":"1991-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Synthesis and anti-inflammatory activity of 5-(1,4-dihydropyridyl)-tetrazol-2-acetic acids, esters and amides.\",\"authors\":\"P Kumar, E E Knaus\",\"doi\":\"\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Thirteen 5-[3-(1,4-dihydropyridyl)]-2H-tetrazol-2-acetic acids (18-30), seventeen esters (4-17, 32, 35, 41) and eight amides (31, 32-34, 36-40) were synthesized in order to investigate the effect of alpha-substituents (R1 = H, Me) and 1,4-dihydropyridyl substituents (R2 = aryl, alkyl; R3 = phenoxy, methoxy or amino) on anti-inflammatory activity. The effects of the R1, R2 or R3-substituents were variable but highly interdependent. The relative order of anti-inflammatory potency was generally acid greater than amide and ester. Methyl 2-methyl-2-(5-[3-(4-phenyl-1-carbamoyl-1,4-dihydropyridyl)]-2H- tetrazol-2-yl) acetate (35) was the most effective anti-inflammatory agent in the group, reducing inflammation 96% at 5 hr after a 50 mg/kg po dose, relative to ibuprofen's 52% inhibition at 5 hr after a 100 mg/kg po dose.</p>\",\"PeriodicalId\":11271,\"journal\":{\"name\":\"Drug design and delivery\",\"volume\":\"7 4\",\"pages\":\"287-94\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"1991-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Drug design and delivery\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Drug design and delivery","FirstCategoryId":"1085","ListUrlMain":"","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Synthesis and anti-inflammatory activity of 5-(1,4-dihydropyridyl)-tetrazol-2-acetic acids, esters and amides.
Thirteen 5-[3-(1,4-dihydropyridyl)]-2H-tetrazol-2-acetic acids (18-30), seventeen esters (4-17, 32, 35, 41) and eight amides (31, 32-34, 36-40) were synthesized in order to investigate the effect of alpha-substituents (R1 = H, Me) and 1,4-dihydropyridyl substituents (R2 = aryl, alkyl; R3 = phenoxy, methoxy or amino) on anti-inflammatory activity. The effects of the R1, R2 or R3-substituents were variable but highly interdependent. The relative order of anti-inflammatory potency was generally acid greater than amide and ester. Methyl 2-methyl-2-(5-[3-(4-phenyl-1-carbamoyl-1,4-dihydropyridyl)]-2H- tetrazol-2-yl) acetate (35) was the most effective anti-inflammatory agent in the group, reducing inflammation 96% at 5 hr after a 50 mg/kg po dose, relative to ibuprofen's 52% inhibition at 5 hr after a 100 mg/kg po dose.