Hydrophobic benzoic acids as inhibitors of influenza neuraminidase.

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Atigadda VR, Brouillette WJ, Duarte F, Babu YS, Bantia S, Chand P, Chu N, Montgomery JA, Walsh DA, Sudbeck E, Finley J, Air GM, Luo M, Laver GW

Hydrophobic benzoic acids as inhibitors of influenza neuraminidase.

Bioorg Med Chem. 1999 Nov;7(11):2487-97.

PubMed ID

10632058 [ View in PubMed

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Abstract

Neuraminidase (NA) plays a critical role in the life cycle of influenza virus and is a target for new therapeutic agents. A new benzoic acid inhibitor (11) containing a lipophilic side chain at C-3 and a guanidine at C-5 was synthesized. The X-ray structure of 4-(N-acetylamino)-5-guanidino-3-(3-pentyloxy)benzoic acid in complex with NA revealed that the lipophilic side chain binds in a newly created hydrophobic pocket formed by the movement of Glu 278 to interact with Arg 226, whereas the guanidine of 11 interacts in a negatively charged pocket created by Asp 152, Glu 120 and Glu 229. Compound 11 was highly selective for type A (H2N2) influenza NA (IC50 1 microM) over type B (B/Lee/40) influenza NA (IC50 500 microM).

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
4-(N-ACETYLAMINO)-3-[N-(2-ETHYLBUTANOYLAMINO)]BENZOIC ACID	Neuraminidase	IC 50 (nM)	670000	6.5	37	Details