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 Sep 14
Externally publishedYes

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Derivatives
Degradation
Ionic strength
Osmolar Concentration
Arrhenius plots
Acids
CWJ-a-5
Titration
Solubility
Methanol
Rate constants
Activation energy
Kinetics
Temperature
Water

Keywords

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

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Pharmacology
  • Molecular Medicine

Cite this

Physicochemical properties of CWJ-a-5, a new antitumor 3-arylisoquinoline derivative. / Kim, Ki Eun; Cho, Won Jea; Kim, Tae Sung; Kang, Boo Hyon; Chang, Sun Jae; Lee, Chi Ho; Kim, Dae Duk.

In: Drug Development and Industrial Pharmacy, Vol. 28, No. 7, 14.09.2002, p. 889-895.

Research output: Contribution to journalArticle

Kim, Ki Eun ; Cho, Won Jea ; Kim, Tae Sung ; Kang, Boo Hyon ; Chang, Sun Jae ; Lee, Chi Ho ; Kim, Dae Duk. / Physicochemical properties of CWJ-a-5, a new antitumor 3-arylisoquinoline derivative. In: Drug Development and Industrial Pharmacy. 2002 ; Vol. 28, No. 7. pp. 889-895.
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