Site-specific acid-base properties of tenoxicam

Kristóf Kóczián, Gergely Völgyi, J. Kökösi, B. Noszál

Research output: Article

8 Citations (Scopus)

Abstract

The Hammett approach, as a new deductive tool, was introduced to characterize the otherwise inaccessible minor protonation pathway of tenoxicam (1), the non-steroidal anti-inflammatory drug. A total of eight compounds, constituting a systematic series of side chain-substituted analogues of tenoxicam and piroxicam (2), were synthesized and studied in terms of acid-base properties and Hammett constants to identify the ideal replacement of the unprotonated pyridin-2-yl group, a key moiety in both molecules. Hammett constants of the phenyl substituents have been found to be in a linear correlation with the experimental log K values of the enolate sites, the basic moiety of the extended conjugated system in this family of piroxicam derivatives. Then, a similar correlation was observed for the analogous tenoxicam derivatives. After identifying the 2-aza Hammett constant of the pyridin-2-yl group and the corresponding log K value, the site-specific acid-base properties of tenoxicam could be quantitated. This novel method is assessed to be a fine-tuning tool to find the ideal substituent by using analogue-based deductive method to obtain site-specific constants of the minor protonation/deprotonation pathway in drugs and biomolecules. The tenoxicam microconstant values indicate that the enolate moiety is of extremely low basicity (reflected by the log kO = 3.70 and log kO N = 1.09 values), which can, however, be interpreted in terms of the peculiar ring system and the overwhelming electron-withdrawing effects of the adjacent heteroatoms. A diagram depicting the pH-dependent distribution of 1 microspecies is also presented.

Original languageEnglish
Pages (from-to)1681-1690
Number of pages10
JournalHelvetica Chimica Acta
Volume90
Issue number9
DOIs
Publication statusPublished - 2007

Fingerprint

tenoxicam
Protonation
Derivatives
Deprotonation
acids
Acids
Biomolecules
Piroxicam
Alkalinity
drugs
Tuning
analogs
Molecules
Electrons
Pharmaceutical Preparations
diagrams
tuning
Anti-Inflammatory Agents
rings

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Site-specific acid-base properties of tenoxicam. / Kóczián, Kristóf; Völgyi, Gergely; Kökösi, J.; Noszál, B.

In: Helvetica Chimica Acta, Vol. 90, No. 9, 2007, p. 1681-1690.

Research output: Article

Kóczián, Kristóf ; Völgyi, Gergely ; Kökösi, J. ; Noszál, B. / Site-specific acid-base properties of tenoxicam. In: Helvetica Chimica Acta. 2007 ; Vol. 90, No. 9. pp. 1681-1690.
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