Unsaturated Nucleoside Analogues: Synthesis and Antitumor Activity |
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| Authors: | Shashikant Phadtare David Kessel Jiri Zemlicka |
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| Affiliation: | 1. Department of Michigan Cancer Foundation , Wayne State University School of Medicine , Detroit, Michigan, 48201;2. Departments of Oncology , Wayne State University School of Medicine , Detroit, Michigan, 48201;3. Pharmacology Wayne State University School of Medicine , Detroit, Michigan, 48201;4. Departments of Oncology , Wayne State University School of Medicine , Detroit, Michigan, 48201 |
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| Abstract: | Abstract Five classes of unsaturated nucleoside analogues were investigated as inhibitors of growth of murine leukemia L 1210 culture. The structural types include E ole-fins 1, Z-olefins 2, acetylene derivatives 3, allenes 4 and oxacyclopentenes 5. Compounds of the type 1-3 (X = Cl) were obtained by alkylation of the respective nucleic acid bases or 2-amino-6-chloropurine with E and Z-1,4-dichloro-2-butene or 1,4-di-chloro-2-butyne. Acid hydrolysis of intermediates 1, 2 and 3 (X = CI) led to the corresponding alcohols 1, 2 and 3 (X = OH). Chloroallene 4 (B = Ade, X = CI) was obtained by chlorination of adenallene (B = Ade, X = OH). Compounds of the type 5 were obtained by base-catalyzed cyclization of the respective 2-butynes. A prolonged hydrolysis of compound 2 (B = 2-amino-6-chloropurine, X = CI) gave tricyclic derivative 7. Similar cyclization of 2 (B = Ade, X = CI) afforded a 3, g-bridged adenine 8. Alcohol 2 (B = Ade, X = OH) is a poor substrate for adenosine deaminase as contrasted with compounds 1, 3 and 4 (B = Ade. X = OH). 4-Hydroxybutyl derivative 6 (B = Ade, X = CI) was completely inert. |
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