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 language | English |
|---|---|
| Pages (from-to) | 889-895 |
| Number of pages | 7 |
| Journal | Drug Development and Industrial Pharmacy |
| Volume | 28 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - 2002 Sep 14 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Physicochemical properties of CWJ-a-5, a new antitumor 3-arylisoquinoline derivative
AU - Kim, Ki Eun
AU - Cho, Won Jea
AU - Kim, Tae Sung
AU - Kang, Boo Hyon
AU - Chang, Sun Jae
AU - Lee, Chi Ho
AU - Kim, Dae Duk
PY - 2002/9/14
Y1 - 2002/9/14
N2 - 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.
AB - 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.
KW - Antitumor
KW - CWJ-a-5
KW - Isoquinolone
KW - Physicochemical
UR - http://www.scopus.com/inward/record.url?scp=0036025248&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036025248&partnerID=8YFLogxK
U2 - 10.1081/DDC-120005634
DO - 10.1081/DDC-120005634
M3 - Article
C2 - 12236074
AN - SCOPUS:0036025248
VL - 28
SP - 889
EP - 895
JO - Drug Development and Industrial Pharmacy
JF - Drug Development and Industrial Pharmacy
SN - 0363-9045
IS - 7
ER -