{"title":"组胺h2受体拮抗剂1,4-二氢吡啶类似物的合成及活性研究。","authors":"V K Agrawal, S B Tang, M W Wolowyk, E E Knaus","doi":"","DOIUrl":null,"url":null,"abstract":"<p><p>Compounds of the type Het-CH2-S-CH2-CH2-Y were prepared, in which Het was 2-, 3- or 4-pyridyl, and Y was a derivative of 2-cyano-1,1-iminodiamine or 2-nitro-1,1-ethenediamine in which the terminal nitrogen was incorporated into a 1,4-dihydropyridine ring (general structure 7; X = NCN or CHNO2). Pharmacological testing using the histamine-induced guinea pig atrial chronotropic response indicated that the pyridyl substituent position was a determinant of activity, the activity order within each isomeric series being usually 2-pyridyl greater than 3- and 4-pyridyl. There was no significant difference in activity between otherwise similar compounds derived from 2-cyano-1,1-iminodiamine (7, X = NCN) or 2-nitro-1,1-ethenediamine (7, X = CHNO2). All compounds had a substituent (R) attached to the C-4 position of the dihydropyridine ring, and the nature of the R substituent influenced the H2-antagonist activity, the relative activity order being usually n-Bu greater than Ph greater than Me. In general, the incorporation of the terminal nitrogen into a 1,4-dihydropyridyl ring system favoured biological activity, 1-(2-[(4-Pyridylmethylthio)ethylamino])-1-(1-[3-(4, 4-dimethyloxazolin-2-yl)-4-n-butyl-1,4-dihydropyridyl)-2- cyanoimine (7f) was the most potent H2-receptor antagonist exhibiting an activity approaching that of cimetidine.</p>","PeriodicalId":11271,"journal":{"name":"Drug design and delivery","volume":"6 2","pages":"101-9"},"PeriodicalIF":0.0000,"publicationDate":"1990-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Synthesis and activity of 1,4-dihydropyridine analogues of histamine H2-receptor antagonists.\",\"authors\":\"V K Agrawal, S B Tang, M W Wolowyk, E E Knaus\",\"doi\":\"\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Compounds of the type Het-CH2-S-CH2-CH2-Y were prepared, in which Het was 2-, 3- or 4-pyridyl, and Y was a derivative of 2-cyano-1,1-iminodiamine or 2-nitro-1,1-ethenediamine in which the terminal nitrogen was incorporated into a 1,4-dihydropyridine ring (general structure 7; X = NCN or CHNO2). Pharmacological testing using the histamine-induced guinea pig atrial chronotropic response indicated that the pyridyl substituent position was a determinant of activity, the activity order within each isomeric series being usually 2-pyridyl greater than 3- and 4-pyridyl. There was no significant difference in activity between otherwise similar compounds derived from 2-cyano-1,1-iminodiamine (7, X = NCN) or 2-nitro-1,1-ethenediamine (7, X = CHNO2). All compounds had a substituent (R) attached to the C-4 position of the dihydropyridine ring, and the nature of the R substituent influenced the H2-antagonist activity, the relative activity order being usually n-Bu greater than Ph greater than Me. In general, the incorporation of the terminal nitrogen into a 1,4-dihydropyridyl ring system favoured biological activity, 1-(2-[(4-Pyridylmethylthio)ethylamino])-1-(1-[3-(4, 4-dimethyloxazolin-2-yl)-4-n-butyl-1,4-dihydropyridyl)-2- cyanoimine (7f) was the most potent H2-receptor antagonist exhibiting an activity approaching that of cimetidine.</p>\",\"PeriodicalId\":11271,\"journal\":{\"name\":\"Drug design and delivery\",\"volume\":\"6 2\",\"pages\":\"101-9\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"1990-06-01\",\"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 activity of 1,4-dihydropyridine analogues of histamine H2-receptor antagonists.
Compounds of the type Het-CH2-S-CH2-CH2-Y were prepared, in which Het was 2-, 3- or 4-pyridyl, and Y was a derivative of 2-cyano-1,1-iminodiamine or 2-nitro-1,1-ethenediamine in which the terminal nitrogen was incorporated into a 1,4-dihydropyridine ring (general structure 7; X = NCN or CHNO2). Pharmacological testing using the histamine-induced guinea pig atrial chronotropic response indicated that the pyridyl substituent position was a determinant of activity, the activity order within each isomeric series being usually 2-pyridyl greater than 3- and 4-pyridyl. There was no significant difference in activity between otherwise similar compounds derived from 2-cyano-1,1-iminodiamine (7, X = NCN) or 2-nitro-1,1-ethenediamine (7, X = CHNO2). All compounds had a substituent (R) attached to the C-4 position of the dihydropyridine ring, and the nature of the R substituent influenced the H2-antagonist activity, the relative activity order being usually n-Bu greater than Ph greater than Me. In general, the incorporation of the terminal nitrogen into a 1,4-dihydropyridyl ring system favoured biological activity, 1-(2-[(4-Pyridylmethylthio)ethylamino])-1-(1-[3-(4, 4-dimethyloxazolin-2-yl)-4-n-butyl-1,4-dihydropyridyl)-2- cyanoimine (7f) was the most potent H2-receptor antagonist exhibiting an activity approaching that of cimetidine.