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

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:19

Article

Kaur, Harneet¹  Izenwasser, Sari²  Verma, Abha¹  Wade, Dean²  Housman, Amy²  Stevens, Edwin D.¹  Mobley, David L.¹  Trudell, Mark L.¹ 

[1] Univ New Orleans, Dept Chem, New Orleans, LA 70148 USA

[2] Univ Miami, Miller Sch Med, Dept Psychiat & Behav Sci, Miami, FL 33136 USA

关键词: Monoamine transporters;    Neurotransmitters;    Dopamine;    Serotonin;    Norepinephrine;    Tropanes;   

DOI  :  10.1016/j.bmcl.2009.10.087

来源: Elsevier

【 摘 要 】

A series of 3-arylnortrop-2-enes and 3 alpha-arylmethoxy-3 beta-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 3 alpha-arylmethoxy-3 beta-arylnortropanes were generally SERT selective with the 3 alpha-(3,4-dichlorophenylmethoxy)-3 beta phenylnortrop-2-ene (7c) possessing subnanomolar potency (K-i = 0.061 nM). However, 3 alpha-(3,4-dichlorophenylmethoxy)-3 beta-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)]. (C) 2009 Elsevier Ltd. All rights reserved.

【 授权许可】

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