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 language | English |
|---|---|
| Pages (from-to) | 1560-1563 |
| Number of pages | 4 |
| Journal | Journal of Medicinal Chemistry |
| Volume | 39 |
| Issue number | 7 |
| DOIs | |
| State | Published - Mar 29 1996 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Synthesis and ligand binding of η6-(2β-carbomethoxy-3β-phenyltropane) transition metal complexes
AU - Aronson, Blake
AU - Enmon, Jennifer L.
AU - Izenwasser, Sari E
AU - Katz, Jonathan L.
AU - Kelkar, Shreekrishna V.
AU - Luo, Lubin
AU - Nolan, Steven P.
AU - Trudell, Mark L.
PY - 1996/3/29
Y1 - 1996/3/29
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0029974464&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029974464&partnerID=8YFLogxK
U2 - 10.1021/jm9508797
DO - 10.1021/jm9508797
M3 - Article
C2 - 8691489
AN - SCOPUS:0029974464
VL - 39
SP - 1560
EP - 1563
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
SN - 0022-2623
IS - 7
ER -