ISSN:
1573-904X
Keywords:
ICRF-187 (ADR-529)
;
hydrolysis
;
pH-rate profile
;
imide
;
acidic degradation
;
bell-shaped profile
;
facilitation
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Abstract The hydrolysis of the cardioprotectant and anticancer agent, ICRF-187 (or ADR-529) and the structurally similar model compound, 4-methylpiperazine-2,6-dione (4-MP), was investigated in the acid to neutral pH range at 25°C and an ionic strength of 0.5 (sodium chloride). Their solution stability was shown to be compromised compared to 3-methylglutarimide (3-MG) and other imides. It appears that the tertiary piperazine nitrogens of ICRF-187 and 4-MP significantly contributed to the instability of these compounds over this pH range. Unexpectedly, bell-shaped curves were observed in the pH-rate profiles. A change in the rate-determining step from tetra-hedral intermediate formation in the weakly acidic pH region to breakdown of the tetrahedral intermediate in the more acidic pH regions was proposed as an explanation for the bell-shaped curves. The piperazine nitrogen was implicated in the hydrolytic pathways that occur within these pH regions; the mechanism of involvement was dependent on the state of ionization of the parent molecule and the tetrahedral intermediate.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1015868209198
Permalink
