PMID: 10732976Mar 25, 2000

Syntheses of R and S isomers of AF-DX 384, a selective antagonist of muscarinic M2 receptors

Bioorganic & Medicinal Chemistry
J MartinM C Lasne

Abstract

Enantiomers of 5,11-dihydro-11-[2-[2-[(N,N-dipropylaminomethyl)piperidin-1- yl]ethylamino]-carbonyl]-6H-pyrido[2,3-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.

References

Feb 7, 1992·Journal of Medicinal Chemistry·D I ScopesA Naylor
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Citations

Nov 15, 2000·Bioorganic & Medicinal Chemistry Letters·M H ParkerC G Brouillette
Feb 20, 2019·Organic & Biomolecular Chemistry·Matthew B GilettoJetze J Tepe
Feb 8, 2002·Journal of Medicinal Chemistry·Masaaki SawaHirosato Kondo

Related Concepts

5,11-dihydro-11-(((2-(2-((dipropylamino)methyl)-1-piperidinyl)ethyl)amino)carbonyl)-6H-pyrido(2,3-b)(1,4)-benzodiazepin-6-one methanesulfonate
Metazoa
Cyclodextrins
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Antispasmodic Effect
Pirenzepin von ct
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Molecular Stereochemistry

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