Synthesis, chemical reactivity, and antileukemic activity of 5-substituted 6,7-bis(hydroxymethyl)pyrrolo[1,2-c]thiazole biscarbamates and the corresponding sulfoxides and sulfones.
A series of bis(N-methylcarbamate) and bis[N-(2-propyl)carbamate] derivatives of 5-substituted 6,7-bis(hydroxy-methyl)pyrrolo[1,2-c]thiazoles was prepared. The compounds were tested for activity in vivo against P388 lymphocytic leukemia, and the chemical reactivities of the compounds were compared by using the model nucleophile 4-(4-nitrobenzyl)pyridine (NBP). The 5-(3,4-dichlorophenyl)-substituted biscarbamates 6b, 8b, and 12b were inactive and unreactive toward NBP. The 5-methyl-substituted biscarbamates 6a, 7a, 8a, 9a, 12a, and 13a were all active against murine P388 lymphocytic leukemia. The chemical reactivities of the active compounds depended on the oxidation state of the sulfur. The reactivity toward NBP followed the order S greater than SO much greater than SO2. The sulfones 12a and 13a are the most active compounds in this series, and their lack of reactivity toward NBP led to the suggestion that 12a and 13a are activated in vivo.
Anderson
W K
WK
Department of Medicinal Chemistry, School of Pharmacy, State University of New York at Buffalo 14260.
Mach
R H
RH
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002219:Carbamates / Q000138:chemical synthesis* / Q000494:pharmacology; D007941:Leukemia P388 / Q000188:drug therapy*; D007942:Leukemia, Experimental / Q000188:drug therapy*; D051379:Mice; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000138:chemical synthesis / Q000494:pharmacology; D013454:Sulfoxides / Q000138:chemical synthesis / Q000494:pharmacology; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology
D000970:Antineoplastic Agents; D002219:Carbamates; D013450:Sulfones; D013454:Sulfoxides; D013844:Thiazoles