Synthesis of New Molecules Based on 1-pyrindane Ring as a New Strategy in the Neurodegenerative Diseases Treatment

Neurodegenerative diseases are one of the major causes of death in aged population all over the world. The Alzheimer\'s disease (AD) is the most common amongst these, followed by the Parkinson\'s disease (PD). The existing therapies (selegiline and rasagiline, propargylaminic drugs usually used in PD treatment as monoamine oxidase-B inhibitors) are still very far from doctor and patient\'s expectations. In this way, the drawing of new therapeutical neuroprotective agents is a great challenge, in order to improve the effectiveness of the existing drugs, or to introduce new alternative therapies. In this work, we describe the synthesis of new propargylic derivatives based on 1-pyrindane ring as a new strategy in the treatment of neurodegenerative diseases. The synthesis was done in due to provide enough number of new compounds endowed with molecular diversity in the pentacyclic ring from 6,7-dihydro-5H-cyclopenta[b]pyridine, commercially available, and 2-bromo-4-methyl-6,7-dihydro-5H-cyclopenta[b]pyridine, easily obtained after bromination of the product of the Sakurai-Midorikawa cyclization between cyclopentanone and ethyl acetoacetate in the presence of ammonium acetate. Classic synthetic methodologies were used, in order to prepare different chemical precursors which will enhance the chemical diversity. In a first step, racemic mixtures was obtained, the enantiomeric pure compounds can be achieved through chemical or enzymatic resolution of the racemates or through enantioselective synthetic processes. In conclusion, a new class of 1-pyrindane derivatives was synthetized, whose synthesis revealed to be effective and simple. After all, the compounds will be evaluated by MAO, AchE and BchE inhibitory activity measure, using selegiline and rasagiline as standards. References · Mechanisms of Ageing and Development 2002, 123 (8), 1081-1086 · Journal of the American Chemical Society 1958, 80 (23), 6254-6257 · Organic & Biomolecular Chemistry 2006, 4 (5), 877-885 · J. Org. Chem. 2004, 69 (15), 5060-5064 · Bulletin of the Chemical Society of Japan 1968, 41 (1), 165-167.