Synthesis and physicochemical study of a quinoxaline derivative with potencial antineoplasic or anti-HIV activity

Article abstract of DOI:10.3390/50300358

Kinetics of the synthesis of 3-[3-quinoxaline(1H)-one]propionic acid (I) were performed. This compound was achieved from reaction between o-phenylenediamine and α-ketoglutaric acid under different experimental conditions, and it was sent to the National Cancer Institute (USA) for its pharmacological evaluation.

Full text of DOI:10.3390/50300358

358
Molecules 2000, 5
Synthesis and Physicochemical Study of a Quinoxaline
Derivative with Potencial Antineoplasic or Anti-HIV Activity
Gabriela A. Rodrigo, Diana G., Bekerman, Adriana E. Robinsohn and Beatriz M. Fernández*
Department of Organic Chemistry. Faculty of Pharmacy and Biochemistry. University of Buenos Ai-
res. (1113) Junin 956. Buenos Aires, Argentina
E-mail: bmfernan@ffyb.uba.ar
* Author to whom correspondence should be addressed.
Abstract: Kinetics of the synthesis of 3-[3-quinoxaline(1H)-one]propionic acid (I) were
performed. This compound was achieved from reaction between o-phenylenediamine and α-
ketoglutaric acid under different experimental conditions, and it was sent to the National
Cancer Institute (USA) for its pharmacological evaluation.
Introduction
Trying to gain more insight into the nature of heterobicyclic chromophores, leading to potential an-
titumoral compounds [1], we analyzed the influence of an alkylcarboxilic chain in the C-3 of the het-
erocycle I upon the pharmacological activity [2].
N
COOH
N
H
O
I
Experimental
Anelation was achieved by reaction of o-phenylenediamine with α-ketoglutaric acid in organic sol-
vents and also in aqueous buffer solutions over a pH range –0.24 -11.5, at room temperature. Kinetics
were performed by UV spectrophotometry at 350 nm.
Compound I was insoluble in water so it was transformed into its ammonium salt in order to able
the evaluation of its biological activity.

359
Molecules 2000, 5
Results and Discussion
Compound I was obtained with good yields (85%) in lab-scale using anhydrous methanol as reac-
tion solvent at room temperature. It was identified by qualitative and quantitative analysis and also by
its spectroscopic properties (UV, IR, 1H NMR).
Kinetic studies determined that two competitive reactions take place in acidic buffers (pH –0.24-
5.8) with a pseudo first-order rate constant for I formation, kobs = 2.18 ± 0.05 x 10-2 min-1. The reaction
is not catalyzed by acids and occurs via formation of several open intermediates.
It is concluded that the presence of the alkylcarboxilic chain in C-3 of the heterocycle is responsible
for the lack of reactivity, not only in basic buffer solutions but also in organic non-polar solvents, if
compound I is compared with other non-acidic quinoxalinone derivatives descripted previously [3,4].
Acknowledgements: We thank to Karina Piton and Laura Belinque for their technical assistance.
References and Notes
1. Nasr, M. et al. J. Pharm. Sci. 1985, 74, 831.
2. Palmer,B. et al. J. Med. Chem.1988, 31, 707.
3. Abasolo M. I. et al. J. Heterocyclic Chem.1987, 24, 1771.
4. Rodrigo, G. A. et al. J. Heterocyclic Chem. 1997, 34, 1.