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Synthesis, Brain Antihypoxic Activity and Cell Neuroprotection of Ester Derivatives of 7-Theophylline acetic acid | Abstract

Der Pharma Chemica
Journal for Medicinal Chemistry, Pharmaceutical Chemistry, Pharmaceutical Sciences and Computational Chemistry

ISSN: 0975-413X
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Abstract

Synthesis, Brain Antihypoxic Activity and Cell Neuroprotection of Ester Derivatives of 7-Theophylline acetic acid

Author(s): Alexander B. Zlatkov, Plamen T. Peikov , Jose Rodriguez-Alvarez , Irina Nikolova , Nikolai . Danchev

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-, IRand 1H-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 LD50, 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.


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