Syntheses of R and S isomers of AF-DX 384, a selective antagonist of muscarinic M2 receptors |
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Authors: | Martin J Deagostino A Perrio C Dauphin F Ducandas C Morin C Desbène P L Lasne M C |
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Institution: | Laboratoire de Chimie Moléculaire et Thio-organique, (CNRS UMR 6507), Institut des Sciences de la Matière et du Rayonnement, Caen, France. |
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Abstract: | Enantiomers of 5,11-dihydro-11-2-2-(N,N-dipropylaminomethyl)piperidin-1- yl]ethylamino]-carbonyl]-6H-pyrido2,3-b]1,4]benzodiazepin-6-one (AF-DX 384) 1, have been synthesized from (S)-(+) and (R)-(-)-2-N,N-dipropylaminomethyl]piperidine 4. The enantiomeric excess of 1 has been determined by capillary electrophoresis by using the alpha-highly sulphated cyclodextrin (alpha-HSCD) as chiral selector within the running electrolyte. (S)-(+)-(4) was prepared from (S)-(-)-pipecolic acid in a 4-step procedure (overall yield: 30%, ee: 99%) and (R)-(-)-AF-DX 384 from (R)-(+)-pipecolic acid. The (R)-(-) isomer exhibited in vitro a 23-fold higher affinity than its enantiomer (S)-(+) towards muscarinic receptors of subtype 2. |
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