title: Design and synthesis of 3,5-disubstituted boron-containing 1,2,4-oxadiazoles as potential combretastatin A-4 (CA-4) analogs.
abstract: 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 thecis-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.
authors.affiliation: Department of Surgery, Weill Cornell Medical College, Cornell University, New York, NY 10065, USA.
authors.forename: Bhaskar C
authors.initials: BC
authors.lastname: Das
authors.forename: Xiang-Ying
authors.initials: XY
authors.lastname: Tang
authors.forename: Patrick
authors.initials: P
authors.lastname: Rogler
authors.forename: Todd
authors.initials: T
authors.lastname: Evans
keywords: 3,5-Disubstituted 1,2,4-oxadiazole; Bioisosteres; Boron-containing CA4 compound; Combretastatin A-4; Tubulin; Vascular disrupting agent
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