3-Pyrroline N-oxide bis(carbamate) tumor inhibitors as analogues of indicine N-oxide.
The 2,3-bis[[(N-methylcarbamoyl)oxy]methyl]-3-pyrroline 1-oxide 5 was synthesized and tested in the murine P388 lymphocytic leukemia model. The compound showed significant reproducible activity and was more potent than indicine N-oxide. 1-Methyl-2-phenyl-3,4-bis[[(N-2- propylcarbamoyl)oxy]methyl]-3-pyrroline N-oxide (6) was less active than 5, and the 5,5-dimethyl analogue of 6, the pyrroline N-oxide 7, was inactive. The N-oxide 7 cannot be converted to a pyrrole in vivo because of the gem-dimethyl substitution at C-5.
Anderson
W K
WK
Department of Medicinal Chemistry, School of Pharmacy, State University of New York at Buffalo 14260.
Milowsky
A S
AS
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D007941:Leukemia P388 / Q000188:drug therapy; D051379:Mice; D011758:Pyrroles / Q000494:pharmacology; D011763:Pyrrolizidine Alkaloids / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D011758:Pyrroles; D011763:Pyrrolizidine Alkaloids; C013095:indicine-N-oxide