IRREVERSIBLE ENZYME INHIBITORS .159. EFFECT OF SUBSTITUTION ON TRANSPORT AND ISOZYME SPECIFICITY OF P-(4,6-DIAMINO-1,2-DIHYDRO-2,2-DIMETHYL-S-TRIAZIN-L-YL)-O-CHLOROPHENOXYACETAMIDO-BENZENESULFONYL FLUORIDE, AN ACTIVE-SITE-DIRECTED IRREVERSIBLE INHIBITOR OF DIHYDROFOLIC REDUCTASE

被引:9
作者
BAKER, BR
ASHTON, WT
机构
[1] Department of Chemistry, University of California, Santa Barbara
关键词
D O I
10.1021/jm00305a042
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Twelve analogs of the title compound (1) were evaluated as irreversible inhibitors of the dihydrofolic reductase from L1210 mouse leukemia and mouse liver; these thirteen compounds were also evaluated for ability to kill L1210 cells in culture, an approximation to cell-wall transport. None of the compounds was more effective than 1. The amide bridge of 1 is believed to be the major deterrent to good transport. © 1969, American Chemical Society. All rights reserved.
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页码:894 / &
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共 15 条
[1]  
BAKER BR, 1968, J MED CHEM, V11, P666, DOI 10.1021/jm00310a007
[2]   IRREVERSIBLE ENZYME INHIBITORS .158. EFFECT OF BRIDGE MODIFICATION ON SELECTIVE IRREVERSIBLE INHIBITION OF DIHYDROFOLIC REDUCTASE FROM L1210 MOUSE LEUKEMIA AND LIVER BY 2,4-DIAMINO-5-(3,4-DICHLOROPHENYL)-6-[P-(M-FLUOROSULFONYLBENZAMIDOMETHYL)PHENOXYMETHYL]PYRIMIDINE .2. [J].
BAKER, BR ;
VERMEULEN, NM .
JOURNAL OF MEDICINAL CHEMISTRY, 1969, 12 (04) :684-+
[3]   IRREVERSIBLE ENZYME INHIBITORS .154. SOME FACTORS IN CELL WALL TRANSPORT OF ACTIVE-SITE-DIRECTED IRREVERSIBLE INHIBITORS OF DIHYDROFOLIC REDUCTASE DERIVED FROM 5-SUBSTITUTED 2,4-DIAMINOPYRIMIDINES [J].
BAKER, BR ;
MEYER, RB .
JOURNAL OF MEDICINAL CHEMISTRY, 1969, 12 (04) :668-&
[4]   IRREVERSIBLE ENZYME INHIBITORS . 140 . ACTIVE-SITE-DIRECTED IRREVERSIBLE INHIBITORS DERIVED FROM 1-(3-CHLOROPHENYL)-4,6-DIAMINO-1,2-DIHYDRO-2,2-DIMETHYL-S-TRIAZINE [J].
BAKER, BR ;
LOURENS, GJ .
JOURNAL OF MEDICINAL CHEMISTRY, 1969, 12 (01) :95-&
[5]   IRREVERSIBLE ENZYME INHIBITORS . 133 . STUDIES ON DIFFERENTIAL IRREVERSIBLE INHIBITION OF DIHYDROFOLIC REDUCTASE FROM 3 STRAINS OF L1210 LEUKEMIA LIVER SPLEEN AND INTESTINE OF MOUSE [J].
BAKER, BR ;
LOURENS, GJ ;
MEYER, RB ;
VERMEULEN, NM .
JOURNAL OF MEDICINAL CHEMISTRY, 1969, 12 (01) :67-+
[7]  
Baker BR, 1967, DESIGN ACTIVE SITE D
[8]  
DECAT A, 1963, J ORG CHEM, V28, P3426
[9]   FUNGAL DETOXICATION .7. METABOLISM OF 2,4-DICHLORO-PHENOXYACETIC AND 4-CHLORO-2-METHYLPHENOXYACETIC ACIDS BY ASPERGILLUS NIGER [J].
FAULKNER, JK ;
WOODCOCK, D .
JOURNAL OF THE CHEMICAL SOCIETY, 1965, (FEB) :1187-&
[10]   THE SYNTHESIS OF 5-HYDROXY-8-NITROQUINOLINE AND CERTAIN OF ITS DERIVATIVES [J].
FUSON, RC ;
BAUMAN, RA ;
HOWARD, E ;
MARVELL, EN .
JOURNAL OF ORGANIC CHEMISTRY, 1947, 12 (06) :799-806