Hydrophobic benzoic acids as inhibitors of influenza neuraminidase.
Bioorg Med Chem
; 7(11): 2487-97, 1999 Nov.
Article
in En
| MEDLINE
| ID: mdl-10632058
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).
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Orthomyxoviridae
/
Benzoates
/
Neuraminidase
Language:
En
Journal:
Bioorg Med Chem
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
1999
Document type:
Article
Affiliation country: