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

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.