Design, synthesis and preliminary pharmacologic evaluation of 2- aminoindane-quinoline analogs as dopaminergic agents | Abstract

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

ISSN: 0975-413X
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Design, synthesis and preliminary pharmacologic evaluation of 2- aminoindane-quinoline analogs as dopaminergic agents

Author(s): Luテδεツ津δづつュs E. Perdomo Zavarce, Katherin de C. Balza Jimenez, Gustavo A. Acurero Castellano, Ligia B. Angel Migliore, Akram S. Dabian Makarem, Andrテδεツ津δづつゥs R. Faria Quintero, Aaron R. Linero Arrieta1, Mariana V. Zapata Cardenas, Mariagracia Vera Sosa, Rodolfo E. Izquierdo Soto, Biagina de C. Migliore de Angel, Heberto Suテδεツ津δづつ。rez Roca, Anita Israel, Jaime E. Charris Charris, Simテδεツ津δづつウn E. Lテδεツ津δづつウpez Dテδε「ツツ堙δづつエSola, Marテδεツ津δづつュa M. Ramテδεツ津δづつュrez Moran, Jorge E. Angel Guio

In recent years, the study of neurodegenerative diseases has accomplished the development of a Medicinal Chemistry oriented strategy towards the design, synthesis and pharmacological study of a large number of compounds with central dopaminergic activity, but, has not found yet a drug capable to effectively cure these diseases. It is well known that both in Venezuela and particular in the Zulia region of this country, there is a high incidence of neurodegenerative and psychiatric disorders, such as Parkinson's, schizophrenia, mania, depression, tardive dyskinesia diseases, Tourette's disease, drug addiction and eating disorders. This has motivated us to direct our research into this important health area, in the search of a rational development of new drugs. This paper describes the design of analogs of N-[(2-chloro-quinoline)-3-yl-methyl]-4,5-dimethoxy-2-aminoindan hydrochloride (9) and the N-[(2-chloro-7-methyl-quinolin )-3-yl-methyl)]- 4,5-dimethoxy-2-aminoindan hydrochloride (10) as novel agents to counteract some of these pathologies. Their convergent organic synthesis was performed according to the synthetic strategies proposed, and the spectroscopic elucidation of the final products was made by NMR techniques 1H, 13C, DEPT, HETCOR and COSY, confirming their structures. The preliminary pharmacological evaluation in stereotypic behavior, demonstrates their agonistic activities on the central dopaminergic system, validating a ready-witted medicinal chemistry approach in the design of these click type drugs.


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