Synthesis of C-6 Pyrimidine Acyclic Nucleoside Analogs as Potential Antiviral Agents |
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| Authors: | Ling-Yih Hsu Dean S Wise William M Shannon John C Drach Leroy B Townsend |
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| Institution: | 1. School of Pharmacy , National Defense Medical Center , Taipei, Taiwan, Republic of China;2. Department of Medicinal Chemistry , College of Pharmacy , Ann Arbor, Michigan, 48109;3. Department of Biologic and Materials Sciences , School of Dentistry, University of Michigan , Ann Arbor, Michigan, 48109;4. Microbiology Research Department , Southern Research Institute , Birmingham, Alabama, 35255 |
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| Abstract: | Abstract A number of pyrimidine acyclic nucleosides in which the acyclic moiety is attached to the C-6 position rather than N-1 of the pyrimidine ring have been prepared. This was accomplished via treatment of lithiated 2,4-dimethoxy-5,6-dimethylpyrimidine, or, 2,4-dimethoxy-6-methylpyrirnidine with 1,3-bis-(benzyloxy)-2-propanone, benzyl chloromethyl ether or oxirane, respectively, to give the corresponding key intermediates 6-3-benzyloxy-2-(benzyloxy)methyl]-2-hydroxypropyl]-2,4-dimethoxy-5-methylpyrimidine (2a), 6-3-Denzyloxy-2-(benzyloxy)methyl]-2-hydroxypropyl]-2,4-dimethoxypyrimidine(2b), 6-(2-benzyloxyethyl)-2,4-dimethoxy-5-methylpyrimidine (3), and2,4-dunethoxy-6-(3-hydroxypropyl)-5-methylpyrimidine (4a). After acidic hydrolysis, followed by debenzylation with boron trichloride these key intermediates were converted to the target C-6 pyrimidine acyclic derivatives. Compounds 6–8b, 11–13, 15, 16, 20, 22, 26, and 29–32 were evaluated for activity against herpes viruses and human immunodeficiency virus. None of the compounds were active against the viruses nor were they cytotoxic at the highest concentration tested. |
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