Synthesis and optical resolution of (R)- and (S)-trans-7-Hydroxy-2-[N-propyl-N-(3'-iodo-2'-propenyl)amino]tetralin: a new D3 dopamine receptor ligand.
An improved method for synthesis and resolution of (R,S)-trans-7-hydroxy-2-[N-propyl-N-(3'-iodo-2'-propenyl)amino]tetralin (trans-7-OH-PlPAT,5), a new D3 dopamine receptor ligand, was reported. Both isomers, (R)-(+)- and (S)-(-)-5, were prepared and characterized. HPLC retention times obtained on a chiral column for these isomers were consistent with those observed for [125I]-(R)-(+)- and (S)-(-)-5. Direct radioiodination of an optically resolved tin precursor, (R)-(+)-7, yielded the desired [125I](R)-(+)-5, which is a simpler method for synthesis of this ligand. Binding studies with membrane preparations containing D3 dopamine receptors expressed in Spodoptera frugiperda (Sf9) cells also suggested that the [125I](R)-(+)-5 is the active isomer (Kd = 0.05 nM). The schemes described may provide an efficient way for synthesizing a large quantity of this new D3 dopamine receptor ligand for in vivo behavior studies.
Chumpradit
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Department of Radiology, University of Pennsylvania, Philadelphia 19104.
Kung
M P
MP
Kung
H F
HF
D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D007457:Iodine Radioisotopes; D007553:Isotope Labeling; D008024:Ligands; D015394:Molecular Structure; D009036:Moths / Q000378:metabolism; D011954:Receptors, Dopamine / Q000378:metabolism*; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013237:Stereoisomerism; D013764:Tetrahydronaphthalenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D014220:Trialkyltin Compounds
D007457:Iodine Radioisotopes; D008024:Ligands; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013764:Tetrahydronaphthalenes; D014220:Trialkyltin Compounds; C081289:7-hydroxy-2-(N-n-propyl-N-(3-iodo-2'-propenyl)-amino)tetralin; C011559:tributyltin