Synthesis and monoamine transporter affinity of 3α-arylmethoxy-3β-arylnortropanes

Harneet Kaur, Sari E Izenwasser, Abha Verma, Dean Wade, Amy Housman, Edwin D. Stevens, David L. Mobley, Mark L. Trudell

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

A series of 3-arylnortrop-2-enes and 3α-arylmethoxy-3β-arylnortropanes were synthesized and evaluated for binding affinity at monoamine transporters. The 3-(3,4-dichlorophenyl)nortrop-2-ene (6e) exhibited high affinity for the SERT (Ki = 0.3 nM). The 3α-arylmethoxy-3β-arylnortropanes were generally SERT selective with the 3α-(3.4-dichlorophenylmethoxy)-3βphenylnortrop-2-ene (7c) possessing subnanomolar potency (Ki = 0.061 nM). However, 3α-(3,4-dichlorophenylmethoxy)-3β-phenylnortrop-2-ene (7b) exhibited high affinity at all three transporters [(DAT Ki = 22 nM), (SERT Ki = 6 nM) and (NET Ki = 101 nM)].

Original languageEnglish
Pages (from-to)6865-6868
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume19
Issue number24
DOIs
StatePublished - Dec 15 2009

Fingerprint

3-(3,4-dichlorophenyl)nortrop-2-ene
3-(3,4-dichlorophenylmethoxy)-3-phenylnortrop-2-ene

Keywords

  • Dopamine
  • Monoamine transporters
  • Neurotransmitters
  • Norepinephrine
  • Serotonin
  • Tropanes

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry

Cite this

Synthesis and monoamine transporter affinity of 3α-arylmethoxy-3β-arylnortropanes. / Kaur, Harneet; Izenwasser, Sari E; Verma, Abha; Wade, Dean; Housman, Amy; Stevens, Edwin D.; Mobley, David L.; Trudell, Mark L.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 19, No. 24, 15.12.2009, p. 6865-6868.

Research output: Contribution to journalArticle

Kaur, H, Izenwasser, SE, Verma, A, Wade, D, Housman, A, Stevens, ED, Mobley, DL & Trudell, ML 2009, 'Synthesis and monoamine transporter affinity of 3α-arylmethoxy-3β-arylnortropanes', Bioorganic and Medicinal Chemistry Letters, vol. 19, no. 24, pp. 6865-6868. https://doi.org/10.1016/j.bmcl.2009.10.087
Kaur, Harneet ; Izenwasser, Sari E ; Verma, Abha ; Wade, Dean ; Housman, Amy ; Stevens, Edwin D. ; Mobley, David L. ; Trudell, Mark L. / Synthesis and monoamine transporter affinity of 3α-arylmethoxy-3β-arylnortropanes. In: Bioorganic and Medicinal Chemistry Letters. 2009 ; Vol. 19, No. 24. pp. 6865-6868.
@article{9437203652c245cea2ded002118f23a0,
title = "Synthesis and monoamine transporter affinity of 3α-arylmethoxy-3β-arylnortropanes",
abstract = "A series of 3-arylnortrop-2-enes and 3α-arylmethoxy-3β-arylnortropanes were synthesized and evaluated for binding affinity at monoamine transporters. The 3-(3,4-dichlorophenyl)nortrop-2-ene (6e) exhibited high affinity for the SERT (Ki = 0.3 nM). The 3α-arylmethoxy-3β-arylnortropanes were generally SERT selective with the 3α-(3.4-dichlorophenylmethoxy)-3βphenylnortrop-2-ene (7c) possessing subnanomolar potency (Ki = 0.061 nM). However, 3α-(3,4-dichlorophenylmethoxy)-3β-phenylnortrop-2-ene (7b) exhibited high affinity at all three transporters [(DAT Ki = 22 nM), (SERT Ki = 6 nM) and (NET Ki = 101 nM)].",
keywords = "Dopamine, Monoamine transporters, Neurotransmitters, Norepinephrine, Serotonin, Tropanes",
author = "Harneet Kaur and Izenwasser, {Sari E} and Abha Verma and Dean Wade and Amy Housman and Stevens, {Edwin D.} and Mobley, {David L.} and Trudell, {Mark L.}",
year = "2009",
month = "12",
day = "15",
doi = "10.1016/j.bmcl.2009.10.087",
language = "English",
volume = "19",
pages = "6865--6868",
journal = "Bioorganic and Medicinal Chemistry Letters",
issn = "0960-894X",
publisher = "Elsevier Limited",
number = "24",

}

TY - JOUR

T1 - Synthesis and monoamine transporter affinity of 3α-arylmethoxy-3β-arylnortropanes

AU - Kaur, Harneet

AU - Izenwasser, Sari E

AU - Verma, Abha

AU - Wade, Dean

AU - Housman, Amy

AU - Stevens, Edwin D.

AU - Mobley, David L.

AU - Trudell, Mark L.

PY - 2009/12/15

Y1 - 2009/12/15

N2 - A series of 3-arylnortrop-2-enes and 3α-arylmethoxy-3β-arylnortropanes were synthesized and evaluated for binding affinity at monoamine transporters. The 3-(3,4-dichlorophenyl)nortrop-2-ene (6e) exhibited high affinity for the SERT (Ki = 0.3 nM). The 3α-arylmethoxy-3β-arylnortropanes were generally SERT selective with the 3α-(3.4-dichlorophenylmethoxy)-3βphenylnortrop-2-ene (7c) possessing subnanomolar potency (Ki = 0.061 nM). However, 3α-(3,4-dichlorophenylmethoxy)-3β-phenylnortrop-2-ene (7b) exhibited high affinity at all three transporters [(DAT Ki = 22 nM), (SERT Ki = 6 nM) and (NET Ki = 101 nM)].

AB - A series of 3-arylnortrop-2-enes and 3α-arylmethoxy-3β-arylnortropanes were synthesized and evaluated for binding affinity at monoamine transporters. The 3-(3,4-dichlorophenyl)nortrop-2-ene (6e) exhibited high affinity for the SERT (Ki = 0.3 nM). The 3α-arylmethoxy-3β-arylnortropanes were generally SERT selective with the 3α-(3.4-dichlorophenylmethoxy)-3βphenylnortrop-2-ene (7c) possessing subnanomolar potency (Ki = 0.061 nM). However, 3α-(3,4-dichlorophenylmethoxy)-3β-phenylnortrop-2-ene (7b) exhibited high affinity at all three transporters [(DAT Ki = 22 nM), (SERT Ki = 6 nM) and (NET Ki = 101 nM)].

KW - Dopamine

KW - Monoamine transporters

KW - Neurotransmitters

KW - Norepinephrine

KW - Serotonin

KW - Tropanes

UR - http://www.scopus.com/inward/record.url?scp=71849119845&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=71849119845&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2009.10.087

DO - 10.1016/j.bmcl.2009.10.087

M3 - Article

C2 - 19896846

AN - SCOPUS:71849119845

VL - 19

SP - 6865

EP - 6868

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

SN - 0960-894X

IS - 24

ER -