Physicochemical properties of CWJ-a-5, a new antitumor 3-arylisoquinoline derivative

Ki Eun Kim, Won Jea Cho, Tae Sung Kim, Boo Hyon Kang, Sun Jae Chang, Chi Ho Lee, Dae Duk Kim

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The compound CWJ-a-5 [1-(4-methylpiperazinyl)-3-phenylisoquinoline hydrochloride] is a novel 3-arylisoquinoline derivative which has exhibited potent antitumor activity. As part of an effort to develop a useful formulation for clinical evaluation of this compound, the aqueous stability of CWJ-a-5 as a function of pH, ionic strength, and temperature, as well as its various physicochemical properties, have been examined. The pKa value obtained by potentiometric titration in methanol-water mixtures was 3.61, at 25°C. The aqueous solubility and the apparent partition coefficient of CWJ-a-5 over the pH range 2.08-9.88 were consistent with those expected of a weak acid of similar pKa value. The degradation of CWJ-a-5 was found to follow apparent first-order kinetics. The pH-rate profiles generated at 80°C were accounted for by acid-catalyzed degradation at low pH and base-catalyzed degradation at high pH. The activation energy was determined as 22.12 kcal/mol for the degradation of CWJ-a-5 in a pH2.92 solution with a constant ionic strength of 0.2. Increasing the ionic strength up to 0.9 led to a higher degradation rate constant at pH2.92. However, CWJ-a-5 was very stable even in a pH2.92 solution, and its shelf-life was calculated to be 2.03 years at 25°C from the Arrhenius plot.

Original languageEnglish
Pages (from-to)889-895
Number of pages7
JournalDrug Development and Industrial Pharmacy
Volume28
Issue number7
DOIs
Publication statusPublished - 2002
Externally publishedYes

Keywords

  • Antitumor
  • CWJ-a-5
  • Isoquinolone
  • Physicochemical

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry

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