Available online at www.derpharmachemica.com Scholars Research Library Der Pharma Chemica, 2010, 2(3): 44-51 (http://derpharmachemica.com/archive.html) ISSN 0975-413X 44 www.scholarsresearchlibrary.com Synthesis, Brain Antihypoxic Activity and Cell Neuroprotection of Ester Derivatives of 7-Theophylline acetic acid Alexander B. Zlatkov a* , Plamen T. Peikov a , Jose Rodriguez-Alvarez b , Irina Nikolova c , Nikolai D. Danchev c a Department of Pharmaceutical Chemistry, Faculty of Pharmacy, 2 Dunav Street, 1000 Sofia, Bulgaria. b Departmento de Bioquímica y Biología Molecular, Universidad Autónoma de Barcelona, Spain. c Department of Pharmacology and Toxicology, Faculty of Pharmacy, 2 Dunav Street, 1000 Sofia, Bulgaria. ______________________________________________________________________________ Abstract The synthesis of three ester derivatives of 7-theophylline-acetic acid and hydroxyl group containing compounds was studied by DCC/4-DMAP – mediated esterification under mild conditions. The structures of synthesized compounds were proved by microanalyses, UV-, IR- and 1 H-NMR data. Acute toxicity assessment of the compounds in mice shows less toxicity than standard theophylline. Compounds 3a-c posses depressive activity on CNS (increasing of pentobarbital sleeping time and decreasing of spontaneous locomotor activity). In in vivo experiments of brain anoxic hypoxia, compounds 3a and 3c in a dose 1 / 10 of LD 50 , result in increase of the mean survival time of mice. These results indicate that compounds 3a and 3c are very prospective for further pharmacological and biochemical experiments in relation to the treatment of brain neurodegenerative disorders. Key words: 7-Theophylline acetic acid, esters, acute toxicity, brain antihypoxic activity _____________________________________________________________________________________________ INTRODUCTION Dementia is the most important psychiatric syndrome associated with degenerative brain disease. Alzheimer’s disease (AD) is the most common cause of dementia in the elderly, and its main clinical symptom is global deterioration of cognitive functions. AD appears to result from multiple pathogenic events, including inflammation, hypoxic / ischemic lesions, the symptoms of which may closely mimic primary brain degeneration. The pathogenic role of β-amyloid is also widely accepted [1-4]. Therapeutic approaches based on these pathogenic mechanisms are developing very rapidly in the last decade. One of the recent pharmaceutical research strategies is searching of possible therapeutic agents in the group of purine and xanthine derivatives. According to some data in the literature the asymmetrically substituted xanthines show activity