Synthesis and biological activity of 6H-isoindolo[2,1-a]indol-6-ones, analogues of batracylin, and related compounds.
Closely related to batracylin, 6H-isoindolo[2,1-a]indol-6-ones including 2-nitro- 13a, 2-amino- 14, and 2-diethylaminopropionamide derivative 16 as well as D-ring substituted 13b, 13c or A-ring substituted 13d and 20 analogues, were synthesised and evaluated against L1210 leukaemia. Subsequent treatment of 13b and 13c with N,N-diethylethylenediamine at 180 degrees C, led to compounds 17a and 17b arising from an unexpected opening of the pyrrolidinone ring and amidification of the keto group. Under the same conditions, the dichloro derivative 13d led to the monoalkyl compound 20 which was the most cytotoxic of the series.
Guillaumel
Jean
J
Service de pharmacochimie, UMR 176 CNRS-institut Curie, Paris, France. claude.monnert@curie.fr
Léonce
Stéphane
S
Pierré
Alain
A
Renard
Pierre
P
Pfeiffer
Bruno
B
Arimondo
Paola B
PB
Monneret
Claude
C
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D051379:Mice; D015394:Molecular Structure; D011799:Quinazolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D006571:Heterocyclic Compounds; D007211:Indoles; D011799:Quinazolines; C057924:batracylin