Comparison of the Chemical Reactivities and Antineoplastic Activities of α,ß-, ß,ß’-,and α,α^/-Bis[[[(2-propylamino)carbonyl]oxy]methyl]-Substituted Pyrroles

The bis[N-(2-propyl)carbamate] derivatives of 2,3-bis(hydroxymethyl)-4,5-diphenyl- 1-methylpyrrole (4a), 3,4-bis-(hydroxymethyl)-2,5-diphenyl-1 -methylpvrrole (4b), 2,4-bis(hydroxymethyl)-3,5-diphenyl-1-methylpyrrole (4c), and 2,5-bis(hydroxymethyl)-3,4-diphenyl-l-methylpyrrole (4d) were synthesized and the reactivities of the four compounds were compared using the model nucleophile 4-(p-nitrobenzyl) pyridine (NBP). No significant correlation was seen between NBP reactivity and either toxicity or antineoplastic activity in this series. Three compounds 4a, 4b, and 4c gave significant reproducible activity against P388 lymphocytic leukemia; the a,a’-bis(carbamate) 4d was inactive. The α,ß-and α,ß’-bis(carbamates) 4a and 4c were evaluated against a panel of mouse tumor homografts and human tumor xenografts implanted under the kidney capsule of mice.