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

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

doi:10.1016/j.bmcl.2009.10.087

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

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

Psychiatry & Behavioral Sciences

Research output: Contribution to journal › Article

5 Scopus citations

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 (K_i = 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 (K_i = 0.061 nM). However, 3α-(3,4-dichlorophenylmethoxy)-3β-phenylnortrop-2-ene (7b) exhibited high affinity at all three transporters [(DAT K_i = 22 nM), (SERT K_i = 6 nM) and (NET K_i = 101 nM)].

Original language	English (US)
Pages (from-to)	6865-6868
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	19
Issue number	24
DOIs	https://doi.org/10.1016/j.bmcl.2009.10.087
State	Published - Dec 15 2009

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

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Kaur, H., Izenwasser, S., Verma, A., Wade, D., Housman, A., Stevens, E. D., Mobley, D. L., & Trudell, M. L. (2009). Synthesis and monoamine transporter affinity of 3α-arylmethoxy-3β-arylnortropanes. Bioorganic and Medicinal Chemistry Letters, 19(24), 6865-6868. https://doi.org/10.1016/j.bmcl.2009.10.087

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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)].",

keywords = "Dopamine, Monoamine transporters, Neurotransmitters, Norepinephrine, Serotonin, Tropanes",

author = "Harneet Kaur and Sari Izenwasser and Abha Verma and Dean Wade and Amy Housman and Stevens, {Edwin D.} and Mobley, {David L.} and Trudell, {Mark L.}",

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AU - Kaur, Harneet

AU - Izenwasser, Sari

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

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