Discovery of substituted 3,4-diphenyl-thiazoles as a novel class of monoamine transporter inhibitors through 3-D pharmacophore search using a new pharmacophore model derived from mazindol.
Substituted 3,4-diphenyl-1,3-thiazols were identified as a class of novel and potent monoamine transporter inhibitors through a 3-D pharmacophore search using a new pharmacophore model derived from mazindol. The most potent compound (13) has K(i) values of 24 and 23 nM in binding to dopamine transporter and inhibition of dopamine reuptake, respectively.
Enyedy
Istvan J
IJ
Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109-0934, USA.
Wang
Jiansuo
J
Zaman
Wahiduz A
WA
Johnson
Kenneth M
KM
Wang
Shaomeng
S
D001665:Binding Sites; D001713:Biphenyl Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D003042:Cocaine / Q000031:analogs & derivatives* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D008024:Ligands; D008454:Mazindol / Q000737:chemistry* / Q000494:pharmacology; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D009419:Nerve Tissue Proteins; D009638:Norepinephrine / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
D001713:Biphenyl Compounds; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D008024:Ligands; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D013844:Thiazoles; D012701:Serotonin; C021279:(1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester; D008454:Mazindol; D003042:Cocaine; D004298:Dopamine; D009638:Norepinephrine