Synthesis and evaluation of Janus type nucleosides as potential HCV NS5B polymerase inhibitors

Zhou, Longhu; Amblard, Franck; Zhang, Hongwang; McBrayer, Tamara R.; Detorio, Mervi; Whitaker, Tony; Coats, Steven J.; Schinazi, Raymond F.

doi:10.1016/j.bmcl.2013.03.077

Cited by 8 publications

(11 citation statements)

References 20 publications

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“…Because of the electron withdrawing properties of the cyano group, the neibouring 8-bromo group could be easily substituted by the nucleophilic reagent. This phenomenon was also found in other 7-deazapurine nucleosides [ 18 , 19 , 20 ]. To depress the side reaction, various methylhydrazine from different commercial sources and a variety of solvents were investigated.…”

Section: Resultssupporting

confidence: 70%

An Expedient Total Synthesis of Triciribine

Ruan

Ding

et al. 2017

Molecules

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In the present paper, we report an expedient total synthesis of triciribine, a tricyclic 7-deazapurine nucleoside and protein kinase B (AKT ) inhibitor, in 35% overall yield. Our synthesis route features a highly regioselective substitution of 1-N-Boc-2-methylhydrazine and a trifluoroacetic acid catalyzed one-pot transformation which combined the deprotection of the tert-butylcarbonyl (Boc) group and ring closure reaction together to give a tricyclic nucleobase motif.

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Section: Resultssupporting

confidence: 70%

An Expedient Total Synthesis of Triciribine

Ruan

Ding

et al. 2017

Molecules

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“…Pyrimido‐fused nucleosides are also called dual bases or Janus‐type tricyclic nucleosides because they can present Watson‐Crick donor/acceptor array of one nucleobase on one face and different donor/acceptor array on the other face and therefore can form stable base pairs with two different complementary nucleobases. The Janus‐type nucleobases such as 41a‐b showed only moderate (micromolar) cytotoxic activities and later on they became conceived more as antivirals …”

Section: Cytotoxic Nucleosidesmentioning

confidence: 99%

“…The Janus-type nucleobases such as 41a-b showed only moderate (micromolar) cytotoxic activities and later on they became conceived more as antivirals. 91,92 Most of the benzo-fused 7-deazapurine nucleosides prepared so far lack any cytotoxic activity against cancer cell lines ( Fig. 12).…”

Section: Fused Nucleosidesmentioning

confidence: 99%

“…110 Janus-type nucleosides 41ab showed moderate anti-HCV activities (EC 50 = 5.7 and 3 M, respectively) which was accompanied by cytotoxicity toward Vero, CEM, and PBM cell lines. 91 Anti-HCV screening of thieno-fused 7-deazapurine ribonucleosides showed that derivatives 44c,e and 45c-e possess submicromolar activities and do not show any cytotoxic effect against the replicon cells. 95 The anti-HCV potency of these compounds is similar to that of anti-HCV agent mericitabine.…”

Section: Ribonucleosidesmentioning

confidence: 99%

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Pyrrolo[2,3‐d]pyrimidine (7‐deazapurine) as a privileged scaffold in design of antitumor and antiviral nucleosides

Perlíková

Hocek

2017

Medicinal Research Reviews

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Abstract7‐Deazapurine (pyrrolo[2,3‐d]pyrimidine) nucleosides are important analogues of biogenic purine nucleosides with diverse biological activities. Replacement of the N7 atom with a carbon atom makes the five‐membered ring more electron rich and brings a possibility of attaching additional substituents at the C7 position. This often leads to derivatives with increased base‐pairing in DNA or RNA or better binding to enzymes. Several types of 7‐deazapurine nucleosides with potent cytostatic or cytotoxic effects have been identified. The most promising are 7‐hetaryl‐7‐deazaadenosines, which are activated in cancer cells by phosphorylation and get incorporated both to RNA (causing inhibition of proteosynthesis) and to DNA (causing DNA damage). Mechanism of action of other types of cytostatic nucleosides, 6‐hetaryl‐7‐deazapurine and thieno‐fused deazapurine ribonucleosides, is not yet known. Many 7‐deazaadenosine derivatives are potent inhibitors of adenosine kinases. Many types of sugar‐modified derivatives of 7‐deazapurine nucleosides are also strong antivirals. Most important are 2′‐C‐methylribo‐ or 2′‐C‐methyl‐2′‐fluororibonucleosides with anti‐HCV activities (several compounds underwent clinical trials). Some underexplored areas of potential interest are also outlined.

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“…Another attempt to identify novel base containing HCV nucleos(t)ide inhibitors was inspired by Janus linear tricyclic nucleosides (71)(72)(73). 73 Unfortunately, neither of these nucleosides nor a representative phosphoramidate prodrug demonstrated anti-HCV activity.…”

Section: Hepatitis C Virusmentioning

confidence: 99%