Comparison of the chemical reactivities and antineoplastic activities of alpha,beta-, alpha,beta'-, beta,beta'-, and alpha,alpha'-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-methylpyrrole (4b), 2,4-bis(hydroxymethyl)-3,5-diphenyl-1-methylpyrrole (4c), and 2,5-bis(hydroxymethyl)-3,4-diphenyl-1-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 alpha,alpha'-bis(carbamate) 4d was inactive. The alpha,beta- and alpha,beta'-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.