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ID: ALA4325927

Journal: ACS Med Chem Lett

Title: Synthesis, Anti-HBV, and Anti-HIV Activities of 3'-Halogenated Bis(hydroxymethyl)-cyclopentenyladenines.

Authors: Kumamoto H, Imoto S, Amano M, Kuwata-Higashi N, Baba M, Mitsuya H, Odanaka Y, Shimbara Matsubayashi S, Tanaka H, Haraguchi K.

Abstract: Synthesis of 3'-halogeno analogues (5a-d) of 9-[c-4,t-5-bis(hydroxymethyl)-cyclopent-2-en-r-1-yl]-9H-adenine (BCA, 3) was accomplished by means of dual utilization of the vinyl sulfone functional moieties in both 10 and 16 utilizing a SN2' conjugate-addition reaction and a sulfur-extrusive stannylation, respectively. Evaluation of the antiviral activities of 5a-d revealed that introduction of a halogeno-substituent into the 3'-position of (-)-BCA diminished its anti-HIV-1 activity but increased the inhibitory activity for the reverse transcriptase of HBV in that the 3'-fluorinated BCA 5d exhibited the highest activity without significant cytotoxicity.

CiteXplore: 30613328

DOI: 10.1021/acsmedchemlett.8b00374