| Synthesis and monoamine transporter binding properties of 2,3-cyclo analogues of 3beta-(4'-aminophenyl)-2beta-tropanemethanol. | |
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MedLine Citation:
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PMID: 16854064 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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A series of cyclo-3beta-(4-aminophenyl)-2beta-tropanemethanol analogues (5a-m) possessing varying linker groups between the 2- and 3-position on the tropane ring were synthesized and evaluated for their monoamine transporter binding properties. The results show that binding to the dopamine and serotonin transporters (DAT and 5-HTT) is highly dependent on the specific linker used. Cyclo-3beta-(4-aminophenyl)-2beta-tropanemethanol pimelic acid ester/amide (5b) had an IC50 of 3.8 nM at the DAT. Cyclo-3beta-(4-aminophenyl)-2beta-tropanemethanol sebacic acid ester/amide (5e) had a Ki of 1.9 nM at the 5-HTT and was 68- and 737-fold selective for the 5-HTT relative to the DAT and NET. Small changes to the size as well as the electrostatic and hydrophobic properties of the 2,3-linker in 5b or 5e led to much less potent analogues at all three transporters. These results suggest that the high affinity for 5b and 5e at the DAT and 5-HTT may be due to their specific conformational properties. |
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Authors:
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F Ivy Carroll; Bruce E Blough; Xiaodong Huang; Zhe Nie; S Wayne Mascarella; Jeffrey Deschamps; Hernán A Navarro |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Journal of medicinal chemistry Volume: 49 ISSN: 0022-2623 ISO Abbreviation: J. Med. Chem. Publication Date: 2006 Jul |
Date Detail:
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Created Date: 2006-07-20 Completed Date: 2006-08-31 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 9716531 Medline TA: J Med Chem Country: United States |
Other Details:
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Languages: eng Pagination: 4589-94 Citation Subset: IM |
Affiliation:
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Center for Organic and Medicinal Chemistry, Research Triangle Institute, Research Triangle Park, North Carolina 27709-2194, USA. fic@rti.org |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Binding, Competitive Cocaine / analogs & derivatives*, chemical synthesis, chemistry, pharmacology Crystallography, X-Ray Dopamine Plasma Membrane Transport Proteins / metabolism* Hydrophobicity Models, Molecular Molecular Structure Norepinephrine Plasma Membrane Transport Proteins / metabolism* Radioligand Assay Rats Serotonin Plasma Membrane Transport Proteins / metabolism* Static Electricity Structure-Activity Relationship Tropanes / chemical synthesis*, chemistry, pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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DA05477/DA/NIDA NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/4,5,6,7,8,9,10,11,13,17a,18,19,20,21,22,22a-hexadecahydro-23-methyl-14,17-etheno-19,22-imino-1H-cyclohept(c)(1,9)oxaazacyclononadecine-3,12-dione; 0/5,6,7,8,10,14a,15,16,17,18,19,19a-dodecahydro-20-methyl-11,14-etheno-16,19-iminocyclohept(c)(1,9)oxaazacyclohexadecine-3,9(1H,4H)-dione; 0/Dopamine Plasma Membrane Transport Proteins; 0/Norepinephrine Plasma Membrane Transport Proteins; 0/Serotonin Plasma Membrane Transport Proteins; 0/Tropanes; 50-36-2/Cocaine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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