Cocaine addiction is a serious health problem to which there is no uniformly effective medication for its treatment. This disorder has been linked to monoaminergic activity and it is believed that possible therapeutics should target these pathways. Even though sertraline is a well-established serotonin reuptake inhibitor that exists as the cis- isomer, it is less recognized that the trans isomer is also highly potent, but unselective. This study aims to synthesize new analogues of sertraline, in both the cis- and trans- isomeric forms, that will be tested for selectivity against 5-HT, dopamine (DAT), and norepinephrine (NET) binding. The proposed synthetic strategy involves the use of a rhodium catalyzed, C-H insertion/Cope rearrangement-elimination reaction previously developed in the Davies laboratory to rapidly synthesize these analogues. The methodology will then be adapted to a solid phase supported catalyst system for the rapid synthesis of a library of compounds. The data collected from biological testing of these analogues should provide opportunities for the design of medications for the treatment of cocaine addiction. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32DA021969-02
Application #
7284254
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Shih, Ming L
Project Start
2006-09-01
Project End
2008-08-31
Budget Start
2007-09-01
Budget End
2008-08-31
Support Year
2
Fiscal Year
2007
Total Cost
$48,796
Indirect Cost
Name
State University of New York at Buffalo
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
038633251
City
Buffalo
State
NY
Country
United States
Zip Code
14260
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Harkany, Tibor; Mackie, Ken; Doherty, Patrick (2008) Wiring and firing neuronal networks: endocannabinoids take center stage. Curr Opin Neurobiol 18:338-45