{"title":"哌替啶和酮贝酮的4-吡啶和-二氢吡啶类似物的合成及其抗伤活性。","authors":"J K Buolamwini, E E Knaus","doi":"","DOIUrl":null,"url":null,"abstract":"<p><p>The synthesis and antinociceptive activity of 4-pyridylpiperdines (7 and 10) in which the phenyl group pf meperidine (1) or ketobemidone (3) is replaced by 2'-, 3'- or 4'-pyridyl is described. All were active in a rat writhing test, and the results showed that the point of attachment of the pyridyl ring to the 4-position was an important determinant of the activity; the relative potency order was 3'-pyridyl greater than 4'-pyridyl greater than 2'-pyridyl in each of the two series. The most potent compound (half the potency of meperidine) was 4-ethoxycarbonyl-4-(3'-pyridyl)-l-methylpiperidine (7b). This compound, and the corresponding 4'-isomer (7c), were further elaborated to provide 1'-phenyl, 1',6'-dihydropyridine (11), and 1'-phenyl, methyl or n-butyl. 1',2'-dihydropyridine (12) analogues containing an acyl function on the ring nitrogen. The most active compound in this series was 4-[4'-(1'-phenoxycarbonyl-2'-n-butyl-l',2'-dihydropyridyl)]- 4- ethoxycarbonyl-l-methylpiperdine (12k). Though less potent than the parent pyridyl compound (7c), it induced 70% inhibition in the writhing test at a dose of 8 mg/kg sc. [The ED50 for meperidine was 0.6 mg/kg sc.]</p>","PeriodicalId":11271,"journal":{"name":"Drug design and delivery","volume":"7 1","pages":"19-31"},"PeriodicalIF":0.0000,"publicationDate":"1990-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Synthesis and antinociceptive activity of 4-pyridyl and -dihydropyridyl analogues of meperidine and ketobemidone.\",\"authors\":\"J K Buolamwini, E E Knaus\",\"doi\":\"\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The synthesis and antinociceptive activity of 4-pyridylpiperdines (7 and 10) in which the phenyl group pf meperidine (1) or ketobemidone (3) is replaced by 2'-, 3'- or 4'-pyridyl is described. All were active in a rat writhing test, and the results showed that the point of attachment of the pyridyl ring to the 4-position was an important determinant of the activity; the relative potency order was 3'-pyridyl greater than 4'-pyridyl greater than 2'-pyridyl in each of the two series. The most potent compound (half the potency of meperidine) was 4-ethoxycarbonyl-4-(3'-pyridyl)-l-methylpiperidine (7b). This compound, and the corresponding 4'-isomer (7c), were further elaborated to provide 1'-phenyl, 1',6'-dihydropyridine (11), and 1'-phenyl, methyl or n-butyl. 1',2'-dihydropyridine (12) analogues containing an acyl function on the ring nitrogen. The most active compound in this series was 4-[4'-(1'-phenoxycarbonyl-2'-n-butyl-l',2'-dihydropyridyl)]- 4- ethoxycarbonyl-l-methylpiperdine (12k). Though less potent than the parent pyridyl compound (7c), it induced 70% inhibition in the writhing test at a dose of 8 mg/kg sc. [The ED50 for meperidine was 0.6 mg/kg sc.]</p>\",\"PeriodicalId\":11271,\"journal\":{\"name\":\"Drug design and delivery\",\"volume\":\"7 1\",\"pages\":\"19-31\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"1990-12-01\",\"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 antinociceptive activity of 4-pyridyl and -dihydropyridyl analogues of meperidine and ketobemidone.
The synthesis and antinociceptive activity of 4-pyridylpiperdines (7 and 10) in which the phenyl group pf meperidine (1) or ketobemidone (3) is replaced by 2'-, 3'- or 4'-pyridyl is described. All were active in a rat writhing test, and the results showed that the point of attachment of the pyridyl ring to the 4-position was an important determinant of the activity; the relative potency order was 3'-pyridyl greater than 4'-pyridyl greater than 2'-pyridyl in each of the two series. The most potent compound (half the potency of meperidine) was 4-ethoxycarbonyl-4-(3'-pyridyl)-l-methylpiperidine (7b). This compound, and the corresponding 4'-isomer (7c), were further elaborated to provide 1'-phenyl, 1',6'-dihydropyridine (11), and 1'-phenyl, methyl or n-butyl. 1',2'-dihydropyridine (12) analogues containing an acyl function on the ring nitrogen. The most active compound in this series was 4-[4'-(1'-phenoxycarbonyl-2'-n-butyl-l',2'-dihydropyridyl)]- 4- ethoxycarbonyl-l-methylpiperdine (12k). Though less potent than the parent pyridyl compound (7c), it induced 70% inhibition in the writhing test at a dose of 8 mg/kg sc. [The ED50 for meperidine was 0.6 mg/kg sc.]