Synthesis and antileukemic activity of bis[[(carbamoyl)oxy]methyl]- substituted pyrrolo[2,1-a]isoquinolines, pyrrolo[1,2-a]quinolines, pyrrolo[2,1-a]isobenzazepines, and pyrrolo[1,2-a]benzazepines.
A series of bis[[(carbamoyl)oxy]methyl]-substituted pyrrole-fused tricyclic heterocycles were synthesized by using 1,3-dipolar cycloaddition reactions with a trifluoromethanesulfonate salt of an appropriate Resissert compound or with a mesoionic oxazolone intermediate. All of the bis(carbamates) were active in vivo against P388 lymphocytic leukemia with 5,6-dihydro-8-methoxy-1,2- bis(hydroxymethyl)pyrrolo[2,1-a]isoquinoline bis[N-(2-propyl)carbamate] (3c) showing the highest level of activity.
Anderson
W K
WK
Department of Medicinal Chemistry, School of Pharmacy, State University of New York, Buffalo 14260.
Heider
A R
AR
Raju
N
N
Yucht
J A
JA
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use; D001552:Benzazepines / Q000138:chemical synthesis / Q000627:therapeutic use; D002219:Carbamates / Q000138:chemical synthesis* / Q000627:therapeutic use; D007546:Isoquinolines / Q000138:chemical synthesis / Q000627:therapeutic use; D007941:Leukemia P388 / Q000188:drug therapy*; D007942:Leukemia, Experimental / Q000188:drug therapy*; D051379:Mice; D011758:Pyrroles / Q000138:chemical synthesis / Q000627:therapeutic use
D000970:Antineoplastic Agents; D001552:Benzazepines; D002219:Carbamates; D007546:Isoquinolines; D011758:Pyrroles