Design and synthesis of 3,5-disubstituted boron-containing 1,2,4-oxadiazoles as potential combretastatin A-4 (CA-4) analogs |
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| Authors: | Bhaskar C Das Xiang-Ying TangPatrick Rogler Todd Evans |
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| Institution: | a Department of Surgery, Weill Cornell Medical College, Cornell University, New York, NY 10065, USA
b Department of Developmental & Molecular Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA |
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| 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 the cis-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. |
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| Keywords: | 3 5-Disubstituted 1 2 4-oxadiazole Combretastatin A-4 Bioisosteres Vascular disrupting agent Tubulin Boron-containing CA4 compound |
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