The pattern of fluorine substitution affects binding affinity in a small library of fluoroaromatic inhibitors for carbonic anhydrase

Organic Letters

Volumn 1, Issue 2, 1999, Pages 183-185

  Doyon, Jeffrey B ^a   Jain, Ahamindra ^a  

^a SWARTHMORE COLLEGE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CARBONATE DEHYDRATASE INHIBITOR; FLUORINE; OCTANE; WATER;

ARTICLE; BIOLOGICAL MODEL; CHEMISTRY; CRYSTALLOGRAPHY; METABOLISM; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; STRUCTURE ACTIVITY RELATION; SYNTHESIS;

CARBONIC ANHYDRASE INHIBITORS; CRYSTALLOGRAPHY; FLUORINE; MAGNETIC RESONANCE SPECTROSCOPY; MODELS, BIOLOGICAL; OCTANES; STRUCTURE-ACTIVITY RELATIONSHIP; WATER;

EID: 0033614869     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol9905250     Document Type: Article

References (16)

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3. 13C NMR was not used since α, β, and γ fluorines couple to carbon, affording spectra that are too complex to be used to assess purity.
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5. Version 4.02, Oxford Molecular Group, 1998.
6. ds were determined by the procedure described in ref 5.
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8. a of the sulfonamide, which should also increase the affinity of inhibitors, resulting in a more steep LFER.
9. Manuscript in preparation. Preliminary data from calculations at MP2/ 6-31G* suggest that an F⋯H bond provides about 4 kJ/mol.
10. Dunitz, J. D.; Taylor, R. Chem. Eur. J. 1997, 3, 89-98.
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13. 19F NMR spectrum of the complex of the pentafluorobenzyl derivative bound to CA shows that the ortho and meta fluorines are shielded in the bound state, relative to their chemical shift when not bound. This shielding is consistent with conformation II.
14. Wilcox and co-workers have recently presented data that refute this interpretation. Kim, E.; Paliwal, S.; Wilcox, C. S. J. Am. Chem. Soc. 1998, 120, 11192-11193.
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