Synthesis of a highly active new anti-HIV agent 2′,3′-Didehydro-3′-deoxy-4′-ethynylthymidine

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Abstract

Compounds having methyl, vinyl, and ethynyl groups at the 4′-position of stavudine (d4T: 2′,3′-didehydro-3′-deoxythymidine) were synthesized. The compounds were assayed for their ability to inhibit the replication of HIV in cell culture. The 4′-ethynyl analogue (15) was found to be more potent and less toxic than the parent compound stavudine.

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Acknowledgments

This work was financially supported in part by grants from the Japan Health Sciences Foundation (SA14718 to H.T.), Japan Society for the Promotion of Science (KAKENHI No. 15590100 to K.H. and No. 15590020 to H.T.), the Research Foundation for Pharmaceutical Sciences (to K. H.), and NIH USA (RO1 AI 38204 to Y.-C.C).

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