Oseltamivir analogues bearing N-substituted guanidines as potent neuraminidase inhibitors

Caitlin A. Mooney; Stuart A. Johnson; Peter 'T Hart; Linda Quarles Van Ufford; Cornelis A M De Haan; Ed E. Moret; Nathaniel I. Martin

doi:10.1021/jm401977j

Oseltamivir analogues bearing N-substituted guanidines as potent neuraminidase inhibitors

Caitlin A. Mooney, Stuart A. Johnson, Peter 'T Hart, Linda Quarles Van Ufford, Cornelis A M De Haan, Ed E. Moret, Nathaniel I. Martin^*

^*Corresponding author for this work

UIPS - Utrecht Institute for Pharmaceutical Sciences

Utrecht University

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

Abstract

A series of oseltamivir analogues bearing an N-substituted guanidine unit were prepared and evaluated as inhibitors of neuraminidases from four strains of influenza the two most potent analogues identified contain relatively small N-guanidine substituents (N-methyl and N-hydroxyl) and display enhanced inhibition with IC₅₀ values in the low nanomolar range against neuraminidases from wild-type and oseltamivir-resistant strains. Potential advantages of including the N-hydroxyguanidine moiety in neuraminidase inhibitors are also discussed.

Original language	English
Pages (from-to)	3154-3160
Number of pages	7
Journal	Journal of Medicinal Chemistry
Volume	57
Issue number	7
DOIs	https://doi.org/10.1021/jm401977j
Publication status	Published - 10 Apr 2014

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title = "Oseltamivir analogues bearing N-substituted guanidines as potent neuraminidase inhibitors",

abstract = "A series of oseltamivir analogues bearing an N-substituted guanidine unit were prepared and evaluated as inhibitors of neuraminidases from four strains of influenza the two most potent analogues identified contain relatively small N-guanidine substituents (N-methyl and N-hydroxyl) and display enhanced inhibition with IC50 values in the low nanomolar range against neuraminidases from wild-type and oseltamivir-resistant strains. Potential advantages of including the N-hydroxyguanidine moiety in neuraminidase inhibitors are also discussed.",

author = "Mooney, {Caitlin A.} and Johnson, {Stuart A.} and {'T Hart}, Peter and {Quarles Van Ufford}, Linda and {De Haan}, {Cornelis A M} and Moret, {Ed E.} and Martin, {Nathaniel I.}",

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AU - Mooney, Caitlin A.

AU - Johnson, Stuart A.

AU - 'T Hart, Peter

AU - Quarles Van Ufford, Linda

AU - De Haan, Cornelis A M

AU - Moret, Ed E.

AU - Martin, Nathaniel I.

PY - 2014/4/10

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AB - A series of oseltamivir analogues bearing an N-substituted guanidine unit were prepared and evaluated as inhibitors of neuraminidases from four strains of influenza the two most potent analogues identified contain relatively small N-guanidine substituents (N-methyl and N-hydroxyl) and display enhanced inhibition with IC50 values in the low nanomolar range against neuraminidases from wild-type and oseltamivir-resistant strains. Potential advantages of including the N-hydroxyguanidine moiety in neuraminidase inhibitors are also discussed.

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JO - Journal of Medicinal Chemistry

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IS - 7

ER -

Oseltamivir analogues bearing N-substituted guanidines as potent neuraminidase inhibitors

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