Abstract
Ethyl [6-bromo-1-(4-fluorophenylmethyl)-4(1H)-quinolinon-3-yl]-4-hydroxy-2-oxo-3-butenoate 1 and [6-bromo-1-(4-fluorophenylmethyl)-4(1H)-quinolinon-3-yl)]-4-hydroxy-2-oxo-3-butenoïc acid 2 were synthesized as potential HIV-1 integrase inhibitors and evaluated for their enzymatic and antiviral activity, acidic compound 2 being more potent than ester compound 1. X-ray diffraction analyses and theoretical calculations show that the diketoacid chain of compound 2 is preferentially coplanar with the quinolinone ring (dihedral angle of 0-30 degrees ). Docking studies suggest binding modes in agreement with structure-activity relationships.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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4-Quinolones / chemical synthesis
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4-Quinolones / chemistry*
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4-Quinolones / pharmacology
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Butyrates / chemical synthesis
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Butyrates / chemistry*
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Butyrates / pharmacology
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Catalytic Domain
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Computer Simulation
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Crystallography, X-Ray
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HIV Integrase / chemistry*
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HIV Integrase / metabolism
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HIV Integrase Inhibitors / chemical synthesis
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HIV Integrase Inhibitors / chemistry*
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HIV Integrase Inhibitors / pharmacology
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Humans
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Molecular Conformation
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Protein Binding
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Quantum Theory
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Structure-Activity Relationship
Substances
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(6-bromo-1-(4-fluorophenylmethyl)-4(1H)-quinolinon-3-yl)-4-hydroxy-2-oxo-3-butenoic acid
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4-Quinolones
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Butyrates
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HIV Integrase Inhibitors
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HIV Integrase
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p31 integrase protein, Human immunodeficiency virus 1