Synthesis and broad spectrum antiviral evaluation of bis(POM) prodrugs of novel acyclic nucleosides

Manbu  Hamada; Vincent Roy; Tamara R. McBrayer; Tony Whitaker; Cesar Urbina Blanco; Steven Patrick Nolan; Jan Balzarini; Robert Snoeck; Graciela Andrei; Raymond F. Schinazi; Luigi A. Agrofoglio

doi:10.1016/j.ejmech.2013.06.053

Synthesis and broad spectrum antiviral evaluation of bis(POM) prodrugs of novel acyclic nucleosides

Manbu Hamada, Vincent Roy, Tamara R. McBrayer, Tony Whitaker, Cesar Urbina Blanco, Steven Patrick Nolan, Jan Balzarini, Robert Snoeck, Graciela Andrei, Raymond F. Schinazi, Luigi A. Agrofoglio

Research output: Contribution to journal › Article › peer-review

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Abstract

A series of seventeen hitherto unknown ANP analogs bearing the (E)-but-2-enyl aliphatic side chain and modified heterocyclic base such as cytosine and 5-fluorocytosine, 2-pyrazinecarboxamide, 1,2,4-triazole-3-carboxamide or 4-substituted-1,2,3-triazoles were prepared in a straight approach through an olefin acyclic cross metathesis as key synthetic step.

All novel compounds were evaluated for their antiviral activities against a large number of DNA and RNA viruses including herpes simplex virus type 1 and 2, varicella zoster virus, feline herpes virus, human cytomegalovirus, hepatitis C virus (HCV), HIV-1 and HIV-2. Among these molecules, only compound 31 showed activity against human cytomegalovirus in HEL cell cultures with at EC50 of ∼10 μM. Compounds 8a, 13, 14, and 24 demonstrated pronounced anti-HCV activity without significant cytotoxicity at 100 μM.

Original language	English
Pages (from-to)	398-408
Number of pages	11
Journal	European Journal Of Medicinal Chemistry
Volume	67
Early online date	4 Jul 2013
DOIs	https://doi.org/10.1016/j.ejmech.2013.06.053
Publication status	Published - Sept 2013

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title = "Synthesis and broad spectrum antiviral evaluation of bis(POM) prodrugs of novel acyclic nucleosides",

abstract = "A series of seventeen hitherto unknown ANP analogs bearing the (E)-but-2-enyl aliphatic side chain and modified heterocyclic base such as cytosine and 5-fluorocytosine, 2-pyrazinecarboxamide, 1,2,4-triazole-3-carboxamide or 4-substituted-1,2,3-triazoles were prepared in a straight approach through an olefin acyclic cross metathesis as key synthetic step.All novel compounds were evaluated for their antiviral activities against a large number of DNA and RNA viruses including herpes simplex virus type 1 and 2, varicella zoster virus, feline herpes virus, human cytomegalovirus, hepatitis C virus (HCV), HIV-1 and HIV-2. Among these molecules, only compound 31 showed activity against human cytomegalovirus in HEL cell cultures with at EC50 of ∼10 μM. Compounds 8a, 13, 14, and 24 demonstrated pronounced anti-HCV activity without significant cytotoxicity at 100 μM.",

author = "Manbu Hamada and Vincent Roy and McBrayer, {Tamara R.} and Tony Whitaker and {Urbina Blanco}, Cesar and Nolan, {Steven Patrick} and Jan Balzarini and Robert Snoeck and Graciela Andrei and Schinazi, {Raymond F.} and Agrofoglio, {Luigi A.}",

year = "2013",

month = sep,

doi = "10.1016/j.ejmech.2013.06.053",

language = "English",

volume = "67",

pages = "398--408",

journal = "European Journal Of Medicinal Chemistry",

issn = "0223-5234",

publisher = "Elsevier Masson SAS",

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T1 - Synthesis and broad spectrum antiviral evaluation of bis(POM) prodrugs of novel acyclic nucleosides

AU - Hamada, Manbu

AU - Roy, Vincent

AU - McBrayer, Tamara R.

AU - Whitaker, Tony

AU - Urbina Blanco, Cesar

AU - Nolan, Steven Patrick

AU - Balzarini, Jan

AU - Snoeck, Robert

AU - Andrei, Graciela

AU - Schinazi, Raymond F.

AU - Agrofoglio, Luigi A.

PY - 2013/9

Y1 - 2013/9

N2 - A series of seventeen hitherto unknown ANP analogs bearing the (E)-but-2-enyl aliphatic side chain and modified heterocyclic base such as cytosine and 5-fluorocytosine, 2-pyrazinecarboxamide, 1,2,4-triazole-3-carboxamide or 4-substituted-1,2,3-triazoles were prepared in a straight approach through an olefin acyclic cross metathesis as key synthetic step.All novel compounds were evaluated for their antiviral activities against a large number of DNA and RNA viruses including herpes simplex virus type 1 and 2, varicella zoster virus, feline herpes virus, human cytomegalovirus, hepatitis C virus (HCV), HIV-1 and HIV-2. Among these molecules, only compound 31 showed activity against human cytomegalovirus in HEL cell cultures with at EC50 of ∼10 μM. Compounds 8a, 13, 14, and 24 demonstrated pronounced anti-HCV activity without significant cytotoxicity at 100 μM.

AB - A series of seventeen hitherto unknown ANP analogs bearing the (E)-but-2-enyl aliphatic side chain and modified heterocyclic base such as cytosine and 5-fluorocytosine, 2-pyrazinecarboxamide, 1,2,4-triazole-3-carboxamide or 4-substituted-1,2,3-triazoles were prepared in a straight approach through an olefin acyclic cross metathesis as key synthetic step.All novel compounds were evaluated for their antiviral activities against a large number of DNA and RNA viruses including herpes simplex virus type 1 and 2, varicella zoster virus, feline herpes virus, human cytomegalovirus, hepatitis C virus (HCV), HIV-1 and HIV-2. Among these molecules, only compound 31 showed activity against human cytomegalovirus in HEL cell cultures with at EC50 of ∼10 μM. Compounds 8a, 13, 14, and 24 demonstrated pronounced anti-HCV activity without significant cytotoxicity at 100 μM.

U2 - 10.1016/j.ejmech.2013.06.053

DO - 10.1016/j.ejmech.2013.06.053

M3 - Article

SN - 0223-5234

VL - 67

SP - 398

EP - 408

JO - European Journal Of Medicinal Chemistry

JF - European Journal Of Medicinal Chemistry

ER -

Synthesis and broad spectrum antiviral evaluation of bis(POM) prodrugs of novel acyclic nucleosides

Abstract

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