1224567-52-5Relevant academic research and scientific papers
Novel type of prodrug activation through a long-range O,N-acyl transfer: A case of water-soluble CREB inhibitor
Li, Bingbing X.,Xie, Fuchun,Fan, Qiuhua,Barnhart, Kerry M.,Moore, Curtis E.,Rheingold, Arnold L.,Xiao, Xiangshu
supporting information, p. 1104 - 1109 (2014/12/10)
CREB (cAMP response element binding protein) has been shown to play an important role in tumor initiation, progression, and metastasis. We discovered that naphthol AS-E, a cell-permeable CREB inhibitor, presented antiproliferative activity in a broad panel of cancer cell lines in vitro. However, it has limited aqueous solubility. In this report, we described a water-soluble inhibitor (compound 6) of CREB-mediated gene transcription with in vivo anticancer activity. Unexpectedly, compound 6 was found to be a prodrug of compound 12 necessitating an unprecedented long-range O,N-acyl transfer. The rate of this transfer was pH- and temperature-dependent. To the best of our knowledge, this is the first time to show that a long-range O,N-acyl transfer could be exploited as a prodrug activation strategy to improve aqueous solubility. This type of prodrug may be applicable to other structures with spatially arranged hydroxyl amide to improve their aqueous solubility.
NAPHTHAMIDES AS ANTICANCER AGENTS
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Page/Page column 40; 41, (2010/05/13)
A compound (particularly useful for inhibiting cancer) according to formula (I): or a pharmaceutically acceptable salt thereof, wherein: x is 0 or 1; R1-R6 are each independently H, -CN, -NO2, -NO, -OH, halogen, hydroxyalkyl, carboxyl, substituted carboxyl, aminocarbonyl, alkoxy, carbonyl or substituted carbonyl; R7 is H, alkyl, alkyl amino, aminoacyl, hydroxyacyl, heteroaryl, heterocycloalkyi, alkyl heteroaryl or alkyl heterocycloalkyl; R8 is H or alkyl; A is O or N; and Ar is an aryl, substituted aryl, heteroaryl, or substituted heleroaryl, provided that if R7 is H then Ar is aryl substituted with alkyl amino.
