Liquid chromatographic measurement of hydrophobicity constants for N-arylsulfonylglycine aldose reductase inhibitors.
The hydrophobicity constants for a series of aldose reductase inhibitors (ARIs) are determined by reversed-phase liquid chromatography. A series of reference compounds consisting of 23 barbituric acid derivatives are separated on two phenylsilica stationary phases over a range of methanol concentrations (30-80%) in 0.05 M phosphate buffer. Linear regression analysis of the measured log k' data is used to estimate the capacity factor in 100% water (log k'w) for each compound. The log k'w values are regressed against the shake-flask-measured 1-octanol-water partition coefficients, producing a correlation of 0.953. The same procedure is then used to estimate the log k'w values for a large group of ARIs and their log P values, calculated from the established relationship between log k'w and log P from the reference compounds. An initial analysis of the aldose reductase inhibitory activity of these compounds as a function of hydrophobicity alone fails to reveal a clear relationship, demonstrating the need for a multivariant approach for quantitative structure-activity analysis in this series of compounds.
Clark
C R
CR
Department of Pharmacal Sciences, School of Pharmacy, Auburn University, Alabama 36849-5503.
Barksdale
J M
JM
Mayfield
C A
CA
Ravis
W R
WR
DeRuiter
J
J
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D001463:Barbiturates; D001555:Benzene Derivatives / Q000737:chemistry*; D002853:Chromatography, Liquid / Q000379:methods*; D005998:Glycine / Q000031:analogs & derivatives* / Q000737:chemistry; D013450:Sulfones / Q000737:chemistry
D001463:Barbiturates; D001555:Benzene Derivatives; D013450:Sulfones; D000449:Aldehyde Reductase; D005998:Glycine