Synthesis and monoamine transporter affinity of 3alpha-arylmethoxy-3beta-arylnortropanes.
A series of 3-arylnortrop-2-enes and 3alpha-arylmethoxy-3beta-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 3alpha-arylmethoxy-3beta-arylnortropanes were generally SERT selective with the 3alpha-(3.4-dichlorophenylmethoxy)-3betaphenylnortrop-2-ene (7c) possessing subnanomolar potency (K(i)=0.061 nM). However, 3alpha-(3,4-dichlorophenylmethoxy)-3beta-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)].
Kaur
Harneet
H
Department of Chemistry, University of New Orleans, New Orleans, LA 70148, USA.
Izenwasser
Sari
S
Verma
Abha
A
Wade
Dean
D
Housman
Amy
A
Stevens
Edwin D
ED
Mobley
David L
DL
Trudell
Mark L
ML
D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000378:metabolism*; D009662:Nortropanes / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*
C546972:3-(3,4-dichlorophenyl)nortrop-2-ene; C546973:3-(3,4-dichlorophenylmethoxy)-3-phenylnortrop-2-ene; D050483:Dopamine Plasma Membrane Transport Proteins; D050484:Norepinephrine Plasma Membrane Transport Proteins; D009662:Nortropanes; D050486:Serotonin Plasma Membrane Transport Proteins