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 journal › Article

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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

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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 journal › Article

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 H, Izenwasser SE, Verma A, Wade D, Housman A, Stevens ED et al. Synthesis and monoamine transporter affinity of 3α-arylmethoxy-3β-arylnortropanes. Bioorganic and Medicinal Chemistry Letters. 2009 Dec 15;19(24):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.
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AU - Verma, Abha

AU - Wade, Dean

AU - Housman, Amy

AU - Stevens, Edwin D.

AU - Mobley, David L.

AU - Trudell, Mark L.

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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)].

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KW - Serotonin

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