ANTITUMOR AND ANTIVIRAL NUCLEOSIDE ANALOGS

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DESCRIPTION: ( Adapted from Applicant's Abstract). New nucleoside analogues will be prepared and studied as potential antiviral and antitumor agents. These compounds will include: i) Enantiomers of active inhibitors of HIV, adenallene and cytallene. ii) Additional analogues of an allene type including fluoro derivatives and allenediols, iii) spirocyclic analogues of allenes, iv) acetylenic and olefinic acyclic nucleoside analogues and their phosphonates, v) 2'-oxacarbocyclic analogues of nucleosides ("isonucleosides") and vi) triphosphate derivatives of allenes for studies of mechanisms of action of adenallene and cytallene. Antitumor activity and mechanism of action of the active analogues will be studied in vitro and in vivo using murine leukemia L 1210 and a number of other tumor systems including solid tumors. Antiviral effects will be investigated in several assays with DNA and RNA viruses with a particular emphasis on HIV. The appropriate analogues (adenine derivatives) will be tested as substrates for adenosine deaminase.