157422-70-3Relevant academic research and scientific papers
CBI analogues of the duocarmycins and CC-1065
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Page 24, (2010/02/10)
An extensive series of CBI analogues of the duocarmycins and CC-1065 exploring substituent effects within the first indole DNA binding subunit is detailed. In general, substitution at the indole C5 position led to cytotoxic potency enhancements that can be ≧1000-fold providing simplified analogues containing a single DNA binding subunit that are more potent (IC50=2-3 pM) than CBI-TMI, duocarmycin SA, or CC-1065. The increases in cytotoxicity correlate well with accompanying increases in the rate and efficiency of DNA alkylation. This effect is more pronounced with the CBI versus DSA or CPI based analogues. Moreover, this effect is largely insensitive to the electronic character of the C5 substituent but is sensitive to the size, rigid length, and shape (sp, sp2, sp3 hybridization) of this substituent consistent with expectation that the impact is due simply to its presence.
Non-peptidic Inhibitors of Human Leukocyte Elastase. 4. Design, Synthesis, and in Vitro and in Vivo Activity of a Series of β-Carbolinone-Containing Trifluoromethyl Ketones
Veale, Chris A.,Damewood, James R.,Steelman, Gary B.,Bryant, Craig,Gomes, Bruce,Williams, Joseph
, p. 86 - 97 (2007/10/02)
A novel series of human leukocyte elastase (HLE) inhibitors containing the β-carbolinone ring system are reported.The design of these trifluoromethyl ketone-based inhibitors used a combination of structural information obtained from X-ray crystallography
