Synthesis and ligand binding of η6-(2β-carbomethoxy-3β-phenyltropane) transition metal complexes

Blake Aronson, Jennifer L. Enmon, Sari E Izenwasser, Jonathan L. Katz, Shreekrishna V. Kelkar, Lubin Luo, Steven P. Nolan, Mark L. Trudell

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

The transition metal complexes [η6-(2β-carbomethoxy-3β- phenyltropane)]tricarbonylchromium (3) and [η6-(2β-carbomethoxy-3β- phenyltropane)][η5-(pentamethylcyclopentadienyl)]ruthenium(II) triflate (4) were synthesized from 2β-carbomethoxy-3β-phenyltropane (2, WIN 35,065) to further elucidate the influence of substituents on the 3β-aryl on the affinity of the ligand for cocaine-binding sites at the dopamine transporter. The compounds were tested for their ability to displace bound [3H]WIN 35,428 (5) from rat caudate putamen tissue and for their ability to inhibit [3H]dopamine uptake. The binding affinity for 3 was 2-fold greater than those observed for cocaine (1) and 2, while the binding affinity for 4 was found to be 100-fold less than those of 1 and 2. In addition, 3 was equipotent with 1 and 2 in [3H]dopamine uptake inhibition studies, while 4 was 10-fold less potent. The potencies of the complexes 3 and 4 correlated well with the structure-activity relationships of other 2β-carbomethoxy- 3β-aryltropane derivatives. These data further support a pharmacophore model in which the region occupied by the aryl ring is a lipophilic pocket with electropositive character.

Original languageEnglish
Pages (from-to)1560-1563
Number of pages4
JournalJournal of Medicinal Chemistry
Volume39
Issue number7
DOIs
StatePublished - Mar 29 1996
Externally publishedYes

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Coordination Complexes
Cocaine
Transition metals
Dopamine
Ligands
Dopamine Plasma Membrane Transport Proteins
Ruthenium
Putamen
Structure-Activity Relationship
Rats
Binding Sites
Tissue
Derivatives

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Synthesis and ligand binding of η6-(2β-carbomethoxy-3β-phenyltropane) transition metal complexes. / Aronson, Blake; Enmon, Jennifer L.; Izenwasser, Sari E; Katz, Jonathan L.; Kelkar, Shreekrishna V.; Luo, Lubin; Nolan, Steven P.; Trudell, Mark L.

In: Journal of Medicinal Chemistry, Vol. 39, No. 7, 29.03.1996, p. 1560-1563.

Research output: Contribution to journalArticle

Aronson, B, Enmon, JL, Izenwasser, SE, Katz, JL, Kelkar, SV, Luo, L, Nolan, SP & Trudell, ML 1996, 'Synthesis and ligand binding of η6-(2β-carbomethoxy-3β-phenyltropane) transition metal complexes', Journal of Medicinal Chemistry, vol. 39, no. 7, pp. 1560-1563. https://doi.org/10.1021/jm9508797
Aronson, Blake ; Enmon, Jennifer L. ; Izenwasser, Sari E ; Katz, Jonathan L. ; Kelkar, Shreekrishna V. ; Luo, Lubin ; Nolan, Steven P. ; Trudell, Mark L. / Synthesis and ligand binding of η6-(2β-carbomethoxy-3β-phenyltropane) transition metal complexes. In: Journal of Medicinal Chemistry. 1996 ; Vol. 39, No. 7. pp. 1560-1563.
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