Potent, orally active heterocycle-based combretastatin A-4 analogues: synthesis, structure-activity relationship, pharmacokinetics, and in vivo antitumor activity …

…, RW McCroskey, SM Hannick, L Gherke…

Index: Wang, Le; Woods, Keith W.; Li, Qun; Barr, Kenneth J.; McCroskey, Richard W.; Hannick, Steven M.; Gherke, Laura; Credo, R. Bruce; Hui, Yu-Hua; Marsh, Kennan; Warner, Robert; Lee, Jang Y.; Zielinski-Mozng, Nicolette; Frost, David; Rosenberg, Saul H.; Sham, Hing L. Journal of Medicinal Chemistry, 2002 , vol. 45, # 8 p. 1697 - 1711

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Citation Number: 375

Abstract

The synthesis and structure-activity relationship study of a series of compounds with heterocycles in place of the cis double bond in combretastatin A-4 (CA-4) are described. Substituted tosylmethyl isocyanides were found to be the key intermediates in construction of the heterocycles. Cytotoxicities of the heterocycle-based CA-4 analogues were evaluated against NCI-H460 and HCT-15 cancer cell lines. 3-Amino-4-methoxyphenyl and N-methyl ...