Novel C-2 substituted carbapenem derivatives .2. Synthesis and structure-activity relationships of isoxazolidin-2-yl, isoxazolidin-2-yl and 2-pyrazolin-2-yl carbapenems generated using 1,3-dipolar cycloaddition chemistry

被引：12

作者：

Burton, G ^{[1
]}

Clarke, GJ ^{[1
]}

Douglas, JD ^{[1
]}

Eglington, AJ ^{[1
]}

Frydrych, CH ^{[1
]}

Hinks, JD ^{[1
]}

Hird, NW ^{[1
]}

Hunt, E ^{[1
]}

Moss, SF ^{[1
]}

Naylor, A ^{[1
]}

Nicholson, NH ^{[1
]}

Pearson, MJ ^{[1
]}

机构：

[1] SMITHKLINE BEECHAM PHARMACEUT,BETCHWORTH RH3 7AJ,SURREY,ENGLAND

来源：

JOURNAL OF ANTIBIOTICS | 1996年 / 49卷 / 12期

关键词：

D O I：

10.7164/antibiotics.49.1266

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

A series of carbapenems containing novel C-2 semisaturated heterocyclic substituents were synthesised by 1,3 dipolar cycloaddition reactions of nitrile oxides, nitrile imines and a nitrone to 2-vinylcarbapenem. The isoxazoline and isoxazolidine compounds showed potent antibacterial activity but moderate stability to human dehydropeptidase 1 (DHP-I). Stability to DHP-I was improved by methyl substitution in the isoxazoline ring, but at the expense of antibacterial activity. The pyrazolines exhibited excellent stability to DHP-I, but reduced potency against Gram-negative organisms.

引用

页码：1266 / 1274

页数：9

共 8 条

[1] Novel C-2 substituted carbapenem derivatives .1. Synthesis and biological activity of non-aromatic heterocyclic derivatives [J].

Burton, G ;

Clear, NJC ;

Eglington, AJ ;

Guest, AW ;

Hunt, E ;

Naylor, A ;

Pearson, MJ ;

Takle, AK .

JOURNAL OF ANTIBIOTICS, 1996, 49 (12) :1258-1265

[2] 3-CYANOCEPHEMS, AND C-13 HETEROCYCLIC-SUBSTITUTED CEPHEMS VIA 1,3-DIPOLAR CYCLOADDITIONS [J].

FAHEY, JL ;

FIRESTONE, RA ;

CHRISTENSEN, BG .

JOURNAL OF MEDICINAL CHEMISTRY, 1976, 19 (04) :562-565

[3] SYNTHESIS AND ACTIVITY OF POTENT 3-(ISOXAZOLIDIN-5-YL)CEPHALOSPORINS AND 3-(ISOXAZOLIDINIUM-5-YL)CEPHALOSPORINS [J].

HUANG, SP ;

KOYAMA, Y ;

IKEDA, D ;

KONDO, S ;

TAKEUCHI, T .

JOURNAL OF ANTIBIOTICS, 1992, 45 (12) :1939-1948

[4] SYNTHESIS AND ACTIVITY OF 3-(ISOXAZOLIN-5-YL)CEPHALOSPORIN AND 3-(ISOXAZOL-4-YL)CEPHALOSPORIN [J].

KOYAMA, Y ;

HUANG, SP ;

IKEDA, D ;

KONDO, S ;

TAKEUCHI, T .

JOURNAL OF ANTIBIOTICS, 1992, 45 (12) :1930-1938

[5] ORALLY ACTIVE PIVALOYLOXYMETHYL 3-(ISOXAZOLIDIN-5-YL)CEPHALOSPORINS [J].

KOYAMA, Y ;

HUANG, SP ;

IKEDA, D ;

KONDO, S ;

TAKEUCHI, T .

JOURNAL OF ANTIBIOTICS, 1992, 45 (12) :1966-1969

[6]

NAKAGAWA S, 1991, Patent No. 430037

[7] Synthesis and antibacterial activity of 2-(isoxazolidinio-5-yl)carbapenem derivatives [J].

Nishi, K ;

Imuta, M ;

Kimura, Y ;

Miwa, H .

JOURNAL OF ANTIBIOTICS, 1995, 48 (12) :1481-1487

[8] CYCLOADDITION OF ACETYLENES TO 7-ACYLAMINO-3-AZIDOMETHYL-3-CEPHEM-4-CARBOXYLIC ACIDS [J].

WILLNER, D ;

CHENEY, LC ;

JELENEVS.AM .

JOURNAL OF MEDICINAL CHEMISTRY, 1972, 15 (09) :948-&

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