ISSN:
0018-019X
Keywords:
Chemistry
;
Organic Chemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
Using the five therapeutic oxicams 1-5, we showed that isosteric replacements result in remarkable changes in the physicochemical and structural properties of congeners. Thus, the acidity of the phenolic OH group is relatively higher in the oxicams containing a pyridinyl moiety, i.e. in piroxicam (1), tenoxicam (2), and lornoxicam, (3), due to their zwitterionic nature. This consequently influences their lipophilicity profile at different ionization states. Furthermore, partitioning behaviour in octan-l-ol/H2O and heptane/H2O systems suggests an internal H-bond between the enolic OH and the amide C=O group. The anionic oxicams readily partition into the octanol phase at pH 7.4 and not at all into the heptane phase. Only the partition coefficients of oxicams measured in the heptane/H2O system, but not in the octanol/H2O system, correlate with their transfer across the blood-brain barrier. This implies that only the neutral form of oxicams crosses the blood-brain barrier.
Additional Material:
5 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/hlca.19930760208
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