Bruni A. T., Ferreira M. M. C., “Omeprazole a nd Analogue Compounds: A Case Study”. Bournemouth, United Kingdom, 08-13/09/2002: 14th European Symposium on Quantitative Structure-Activity Relationships: Designing Drugs - Problems and Solutions (Euro QSAR 2002), Final Programme Book, Poster No. 051. Section: Session 3 - Modelling the Chemistry.

Poster No: 051
 

    Omeprazole and Analogue Compounds: A Case Study

                         Aline Thaís Bruni and Márcia Miguel Castro Ferreira
Instituto de Química, Universidade Estadual de Campinas, Campinas, SP BRAZIL 13083-970
                                             marcia@iqm.unicamp.br

Omeprazole is a substituted benzimidazole and it presents an optically active center with the
sulfur of the sulfoxide group being the chiral center. It is a pro-drug which can be easily
converted into its respective sulfenamide at low pH. Figure 1 shows the decomposition
reaction of omeprazole (1) to sulfenamide (4). Omeprazole has also some rotational freedom.
Figure 1. Omeprazole decomposition reaction in acid medium.
In this work, omeprazole and analogue compounds have been studied against Heliobacter
pylori action. Heliobacter pylori usually lives in the stomach and requires urease enzyme to
colonize mucus layer.¹ It plays and important role in peptic ulcer disease, and the bacterium
eradication decreases the ulcer recurrence.^2,3 These facts motivate a search to find new
treatments. Besides, some complementary studies about omeprazole behavior were
performed. Conformational aspects, racemization barriers and decomposition reaction (Fig. 1)
were taken in account. Initially, conformational analysis was performed for all compounds.
Quantum chemistry coupled to chemometric methods PCA⁴ were used to find all minimum
energy structures for each drug. The PM3 semi-empirical method implemented in Gaussian
98 package was used to perform conformational analysis and to find the racemization barriers
values. The descriptors and the total energy involved in the decomposition reaction were
calculated by using the ab initio method at Hartree-Fock level (6-31G**), implemented in
Spartan Pro package. The PLS regression method was used to build the QSAR models.
1. B. J. Marshall, Am. J. Gastroenterol., 89 S116 (1994).
2. Y. Glupczynski, A. Burette, Am. J. Gastroenterol., 87 1716 (1992).
3. N. Chiba, B. V. Rao, J. W. Rademaker, R. H. Hunt, Am. J. Gastroenterol., 87 1716 (1992).
4. A. T. Bruni, B. P. Leite, M. M. C. Ferreira, J. Comp. Chem., 23 222 (2002).