期刊
EXPERT OPINION ON THERAPEUTIC PATENTS
卷 10, 期 4, 页码 459-474出版社
TAYLOR & FRANCIS LTD
DOI: 10.1517/13543776.10.4.459
关键词
anticancer drug; benzimidazole; cyclopropaindolone; DNA minor groove alkylator; duocarmycin; mustard; polybenzamide; polypyrrole; pyrrolbenzodiazepine
Agents that alkylate DNA in the minor groove are potent cytotoxins. Together with their potential sequence selectivity of interaction with DNA, they are therefore of great interest as potential anticancer drugs. Work with nitrogen mustards has shown that attachment of the mustard unit to carrier molecules targeted at the minor groove can drastically alter normal patterns of both regio- and sequence-selectivity of alkylation, from reaction primarily at most guanine N7 sites in the major groove (chlorambucil) to a few adenine N3 sites at the 3'-end of poly(A/T) sequences in the minor groove (tallimustine). Similar targeting of pyrrolizidine alkylators has also been reported. However, most recent (1997 - 1999) patent applications in this area have been focused on the cyclopropaindolone class of natural products which alkylate at the N-3 of adenines in runs of adenines.
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