Synthesis of indole derivatives as dopaminergic and serotonergic agents
Abstract
A brief review of dopamine and serotonin pharmacology is presented as well as discussion of the design of compounds with such activities. The thesis project involved the synthesis and subsequent biological evaluation of a series of di-N-substituted 4-(2-aminoethyl)indoles. The previously synthesized di-N-propyl analog (DPAI) is one of the most highly selective presynaptic dopamine agonists, and as such has attracted considerable attention. Our objectives in undertaking this project were to devise a convenient route to the synthesis of symmetrically, as well as unsymmetrically N-substituted compounds. The synthesis was successfully carried out. A series of 4 and 5 substituted indolyl piperazines was also synthesized, which showed promising serotonergic activity. In addition the putative metabolite of DPAI, 6-OH-DPAI was synthesized in an eleven step sequence. Evaluation of these compounds contributed to a further understanding of structure-activity relationships in this series and may lead to other compounds with site selective dopaminergic or serotonergic activity.
Degree
Ph.D.
Advisors
Cassady, Purdue University.
Subject Area
Pharmacology
Off-Campus Purdue Users:
To access this dissertation, please log in to our
proxy server.