In an effort to search for potential therapeutic agents for cocaine addiction, a novel class of compounds was synthesized and evaluated for in vitro dopamine and serotonin transporter affinities. These unique 3ƒÀ-aryl-3ƒ¿-arylmethoxytropane analogues incorporated the structure of dopamine selective 2-substituted-3-phenyltropanes and the design of serotonin selective meperidine derivatives. In general, the 3ƒÀ-aryl-3ƒ¿-arylmethoxytropane analogues exhibited greater potency for the serotonin transporter than the dopamine transporter. The most potent compounds of this series were 3ƒÀ-phenyl-3ƒ¿.(3, 4-dichlorophenyl)methoxy-8.azabicyclo [3.2.1]nortropane (Ki = 0.06 nM) and 3ƒÀ-(4Œ-chlorophenyl)-3ƒ¿.(4-chlorophenyl)methoxy-8. azabicyclo[3.2.1]nortropane (Ki = 0.09 nM) at the serotonin transporter and their binding affinities were equipotent with paroxetine and fluoxetine (Prozac). A series of 8-azabicyclo[3.2.1]oct-2-ene derivatives were synthesized from 3-tropinone based on the structure of triple re-uptake inhibitor, DOV 216, 303. The compounds were designed as potential triple re-uptake inhibitors which could exhibit equipotent affinities at the monoamine transporters for dopamine, serotonin and norepinephrine. A short and efficient synthetic methodology was developed for the synthesis of unique compounds which could exhibit potency for both the dopamine and serotonin transporters. The 3ƒÀ-aryl-3ƒ¿-(4Œ, 4-disubstituteddiphenylmethoxy)tropane analogues were designed as hybrid structures of the dopamine transporter selective benztropines and the serotonin transporter selective meperidine derivatives.
Identifer | oai:union.ndltd.org:uno.edu/oai:scholarworks.uno.edu:td-1586 |
Date | 08 August 2007 |
Creators | Kaur, Harneet |
Publisher | ScholarWorks@UNO |
Source Sets | University of New Orleans |
Detected Language | English |
Type | text |
Format | application/pdf |
Source | University of New Orleans Theses and Dissertations |
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