193225-54-6Relevant academic research and scientific papers
Synthesis and cytotoxicity of 5-amino-1-(chloromethyl)-3-[(5,6,7- trimethoxyindol-2-yl)carbonyl], 1,2 dihydro-3H-benz[e]indole (Amino-seco- CBI-TMI) and related 5-alkylamino analogues: New DNA minor groove alkylating agents
Atwell, Graham J.,Tercel, Moana,Boyd, Maruta,Wilson, William R.,Denny, William A.
, p. 9414 - 9420 (1998)
The first synthesis of seco-CBI-TMI alkylating agents with 5-nitrogen substituents is reported. The parent 5-amino compound was prepared in a 15- step synthesis from 1-hydroxynaphthalene-2-carboxylic acid. Reductive alkylation of the 5-amino compound gave the corresponding 5-methylamino and 5-dimethylamino analogues, while resolution of an intermediate by chiral HPLC allowed preparation of the R and S enantiomers of the 5-amino analogue. Absolute configuration was assigned by X-ray crystallography. The S enantiomer was about 65-fold more cytotoxic than the R enantiomer in cell line assays. The 5-amino and 5-methylamino compounds had in vitro cytotoxicities comparable to that of the known 5-hydroxy analogue (0.2-0.5 nM), while the 5-dimethylamino derivative was about 10-fold less potent. The high potencies of the 5-amino and 5-methylamino analogues make them of interest for the formation of relatively stable amine-based prodrugs.
