114978-79-9Relevant articles and documents
Novel acyclic nucleotides and nucleoside 5'-triphosphates imitating 2',3'- dideoxy-2',3'-didehydronucleotides: Synthesis and biological properties
Shirokova,Tarussova,Shipitsin,Semizarov,Krayevsky
, p. 3739 - 3748 (2007/10/02)
A series of pyrophosphoryl (Z)-(phosphonomethoxy)but-2-enyl derivatives of pyrimidines and purines 9a-d and the corresponding phosphonates 10a-d were synthesized. The prepared compounds contain the phosphonate group as an α- phosphate mimic as well as an
Nucleic Acid Derived Allenols: Unusual Analogues of Nucleosides with Antiretroviral Activity
Phadtare, Shashikant,Zemlicka, Jiri
, p. 5925 - 5931 (2007/10/02)
Racemic 1,2-butadien-4-ols substituted with a nucleic acid base were prepared by a base-catalyzed isomerization of the corresponding 2-butynols.With basic heterocycles such as adenine, cytosine, 5-methylcytosine, or N-guanine, the respective allenes were obtained without difficulty, but with guanine, side reactions were observed.Reaction of 2-butynols in stronger base (1 M NaOH) gave cyclized products-oxacyclopentenes 8a-c. (+/-)-Adenallene (3a) and (+/-)-cytallene (3c) are strong inhibitors of replication of human immunodeficiency virus(HIV) in vitro. (+/-)-Adenallene (3a) and butyne 6a are substrates for adenosine deaminase.Racemic 3a was deaminated quantitatively to (+/-)-hypoxallene (3h), indicating a low stereoselectivity as contrasted with the natural substrate-adenosine.When the deamination was stopped ad ca. 50percent conversion, (-)-adenallene (3a) and (+)-hypoxallene (3h) were obtained.Antiretroviral and adenosine deaminase substrate activities are discussed in terms of the similarity of several steric and stereoelectronic features of allenic derivatives of nucleic bases with those of the corresponding nucleosides or 2',3'-dideoxyribonuclesides.
Potential inhibitors of S-adenosylmethionine-dependent methyltransferases. 11. Molecular dissections of neplanocin A as potential inhibitors of S-adenosylhomocysteine hydrolase
Borcherding,Narayanan,Hasobe,McKee,Keller,Borchardt
, p. 1729 - 1738 (2007/10/02)
A series of 9-(hydroxyalkenyl)purines (adenines and 3-deazaadenines), which are analogues of neplanocin A, were synthesized. The analogues were tested as inhibitors of bovine liver and murine L929 cell S-adenosylhomocysteine (AdoHcy) hydrolase (EC 3.3.1.1) and as inhibitors of vaccinia virus replication in murine L929 cells. Compounds 1b, 2a, 2b, 4a, 4b, 7, 9a, and 9b showed the best inhibitory effects toward bovine liver AdoHcy hydrolase, with compound 4b being the most potent. The compounds that were shown to be the most potent inhibitors of the bovine liver AdoHcy hydrolase all contained an allylic hydroxyl group in the cis position to the adenine or the 3-deazaadenine rings. It was concluded that the cis arrangement of the allylic hydroxyl groups in these acyclic compounds represented the minimum structural requirement of the trihydroxycyclopentenyl ring of neplanocin A to show inhibitory effects against AdoHcy hydrolase. The antiviral effects of these acyclic analogues were significantly less than neplanocin A; however, there appears to be a correlation between the antiviral activity and the inhibition of AdoHcy hydrolase for compounds 2a, 2b, 4a, 4b, and 7. Analogue 4b, which exhibited the best antiviral activity (IC50=70 μM) in this acyclic series, is substantially less potent than neplanocin A (IC50=0.08 μM) as an antiviral agent.
