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Table Of Contents

INTRODUCTION
Neurotransmitters
Table 1. Monoamines and their Drug Targeting
Monoamine Transporters and Their Genes
Serotonin Transporter: Homology and Structure
Mechanism of Serotonin Transporters
Serotonin Hypothesis and Antidepressants
The Serotonin-Selective Reuptake Inhibitors
Table 2. SSRIs Inhibition of Monoamine Neurotransmittersa
Mechanism of Action of SSRIs
Figure 7. Illustrated mechanism of SSRIs activity
The Disadvantages of SSRIs
New Targets for Drug Development
Meperidine Hypothesis
Lead Modification
Transporter Binding Affinity and Inhibition Constant
General Hierarchy of Screening
Preliminary Structure-Activity Relationships of Meperidine Analogues
Synthesis of Meperidine
Objectives and Specific Aims
RESULTS AND DISCUSSION
Attempted Alternative Meperidine Synthesis
Attempted Modification of Ring Closure Step
Synthesis of Aryl-substituted Meperidine Derivatives
Synthesis of Substituted Benzyl 1-methyl-4-aryl-4-carboalkoxy-piperidine
Figure 12. Secondary amines in current market SSRIs
Design of Next Generation SSRIs
Synthesis of N-benzyl-1-methyl-4-aryl-4-methylamine Derivatives (71)
CONCLUSIONS
Figure 12. Meperidine analogue pharmacophore for SERT Binding
EXPERIMENTAL SECTION
REFERENCES
APPENDIX
VITA
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Synthesis and SAR Study of Meperidine Analogues as Selective Sero

Synthesis and SAR Study of Meperidine Analogues as Selective Sero

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Published by Hoa Nguyễn

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Published by: Hoa Nguyễn on Nov 10, 2011
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07/19/2013

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