Hartman Institute for Therapeutic Organ Regeneration

Design and synthesis of 3,5-disubstituted boron-containing 1,2,4-oxadiazoles as potential combretastatin A-4 (CA-4) analogs.

TitleDesign and synthesis of 3,5-disubstituted boron-containing 1,2,4-oxadiazoles as potential combretastatin A-4 (CA-4) analogs.
Publication TypeJournal Article
Year of Publication2012
AuthorsDas BC, Tang X-Y, Rogler P, Evans T
JournalTetrahedron Lett
Volume53
Issue31
Pagination3947-3950
Date Published2012 Aug 01
ISSN0040-4039
Abstract

<p>We have designed and synthesized a small library of 3,5-disubstituted-1,2,4-oxadiazole containing combretastatin A-4 (CA-4) analogs. Our objective is to increase the efficacy of the CA-4 as an anti-tubulin and antimitotic agent by substituting the -alkene bond with one of its bioisosteres, the 1,2,4-oxadiazole ring. We also modified the substituents attached to both of the phenyl rings (ring A and B in Fig. 1) of CA-4 for the purpose of diversifying our analogs based on SAR. These compounds were synthesized via a coupling reaction between an amidoxime and a carboxylic acid in DMF solvent, with HOBt as a base, and utilizing EDCI as a coupling reagent. Using this protocol, we synthesized a small library of 10 compounds with moderate to good yields. A detailed biological study is currently undergoing in our laboratory to evaluate the activity of these compounds.</p>

DOI10.1016/j.tetlet.2012.02.110
Alternate JournalTetrahedron Lett
PubMed ID24039307
PubMed Central IDPMC3771381
Grant ListR01 HL056182 / HL / NHLBI NIH HHS / United States
R21 AA020630 / AA / NIAAA NIH HHS / United States
R37 HL056182 / HL / NHLBI NIH HHS / United States
R56 AI093220 / AI / NIAID NIH HHS / United States

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