Photooxidation of troglitazone, a new antidiabetic drug

Photochem Photobiol. 1996 May;63(5):615-20. doi: 10.1111/j.1751-1097.1996.tb05664.x.

Abstract

Troglitazone (CS-045) is a new oral antidiabetic drug reported to be effective in insulin-resistant diabetes and to show antihypertensive effects. Photooxidation of troglitazone gave the quinone and quinone epoxide as the major final stable products. An intermediate observed by NMR spectroscopy was shown to be the hydroperoxydienone, which is moderately stable at room temperature. The rate constant of singlet oxygen quenching by troglitazone is 2.14 x 10(8) M(-1) s(-1) and the reaction rate constant in acetone-d6 is 8.64 X 10(6) M(-1) s(-1). Only the chroman ring of troglitazone reacts with and quenches singlet oxygen significantly, and its reactivity and products are analogous to those of alpha-tocopherol. The reactivity of CS-45 toward singlet oxygen is much larger than that of the related compounds lacking the chroman ring.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromans / chemistry
  • Chromans / radiation effects*
  • Drug Stability
  • Hypoglycemic Agents / chemistry
  • Hypoglycemic Agents / radiation effects*
  • Kinetics
  • Magnetic Resonance Spectroscopy
  • Molecular Structure
  • Oxidation-Reduction
  • Oxygen
  • Photochemistry
  • Quinones
  • Singlet Oxygen
  • Structure-Activity Relationship
  • Thiazoles / chemistry
  • Thiazoles / radiation effects*
  • Thiazolidinediones*
  • Troglitazone

Substances

  • Chromans
  • Hypoglycemic Agents
  • Quinones
  • Thiazoles
  • Thiazolidinediones
  • Singlet Oxygen
  • Troglitazone
  • Oxygen