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 › peer-review

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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Synthesis and monoamine transporter affinity of 3α-arylmethoxy-3β-arylnortropanes. / Kaur, Harneet; Izenwasser, Sari; 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 › peer-review

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

note = "Funding Information: We thank Dr. Amy Hauck Newman at the NIDA Intramural Research Program, Baltimore, Maryland for the assistance provided to Harneet Kaur in the aftermath of Hurricane Katrina. This research was supported by the National Institute on Drug Abuse ( DA11528 ) and the Louisiana Optical Network Initiative Institute (DLM), supported by the Louisiana Board of Regents Post-Katrina Support Fund Initiative grant LEQSF (2007-12)-ENH-PKSFI-PRS-01. ",

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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.

N1 - Funding Information: We thank Dr. Amy Hauck Newman at the NIDA Intramural Research Program, Baltimore, Maryland for the assistance provided to Harneet Kaur in the aftermath of Hurricane Katrina. This research was supported by the National Institute on Drug Abuse ( DA11528 ) and the Louisiana Optical Network Initiative Institute (DLM), supported by the Louisiana Board of Regents Post-Katrina Support Fund Initiative grant LEQSF (2007-12)-ENH-PKSFI-PRS-01.

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

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KW - Norepinephrine

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