Synthesis and evaluation of 1,4,5,6-tetrahydropyridazine derivatives as influenza neuraminidase inhibitors

L Zhang; M A Williams; D B Mendel; P A Escarpe; X Chen; K Y Wang; B J Graves; G Lawton; C U Kim

doi:10.1016/s0960-894x(99)00280-2

Synthesis and evaluation of 1,4,5,6-tetrahydropyridazine derivatives as influenza neuraminidase inhibitors

Bioorg Med Chem Lett. 1999 Jul 5;9(13):1751-6. doi: 10.1016/s0960-894x(99)00280-2.

Authors

L Zhang¹, M A Williams, D B Mendel, P A Escarpe, X Chen, K Y Wang, B J Graves, G Lawton, C U Kim

Affiliation

¹ Gilead Sciences Inc., Foster City, CA 94404, USA.

PMID: 10406636
DOI: 10.1016/s0960-894x(99)00280-2

Abstract

1,4,5,6-Tetrahydropyridazine derivative 15 and its C-5 epimer 19, which possessed side chains similar to GS4071, were synthesized via a hetero Diels-Alder reaction, and evaluated as influenza neuraminidase inhibitors. Compounds 15 and 19 exhibited a microM range of influenza neuraminidase inhibitory activity.

MeSH terms

Crystallography, X-Ray
Enzyme Inhibitors / chemical synthesis*
Influenza A virus / drug effects*
Influenza A virus / enzymology
Influenza B virus / drug effects*
Influenza B virus / enzymology
Inhibitory Concentration 50
Magnetic Resonance Spectroscopy
Models, Chemical
Models, Molecular
Neuraminidase / antagonists & inhibitors*
Pyridazines / chemical synthesis*
Pyridazines / pharmacology*

Substances

Enzyme Inhibitors
Pyridazines
Neuraminidase