178419-45-9Relevant articles and documents
A chiral synthesis of (-)-spiro[1-azabicyclo[2.2.2]octane-3,5′- oxazolidin-2′-one]: A conformationally restricted analogue of acetylcholine that is a potent and selective α7 nicotinic receptor agonist
Macor, John E.,Mullen, George,Verhoest, Patrick,Sampognaro, Anthony,Shepardson, Bruce,Mack, Robert A.
, p. 6493 - 6495 (2007/10/03)
A direct, short chiral synthesis of the selective α7 nicotinic receptor agonist (-)-spiro[1-azabicyclo[2.2.2]-octane-3,5′-oxazolidin- 2′-one] (AR-R17779) is presented. The key step utilized attack of the dianion of the (R)-HYTRA ester [(R)-(+)-2-hydroxy-1,2,2-triphenylethyl acetate] on quinuclidin-3-one, followed by a selective precipitation of the diasteriomeric tertiary alcohol that led to (S)-(-)-AR-R17779 in two additional steps.
(-)-Spiro[1-azabicyclo[2.2.2]octane-3,5'-oxazolidin-2-one], a Conformationally restricted analogue of acetylcholine, is a highly selective full agonist at the α7 nicotinic acetylcholine receptor
Mullen,Napier,Balestra,Decory,Hale,Macor,Mack,Loch III,Wu,Kover,Verhoest,Sampognaro,Phillips,Zhu,Murray,Griffith,Blosser,Gurley,Machulskis,Zongrone,Rosen,Gordon
, p. 4045 - 4050 (2007/10/03)
Neuronal nicotinic acetylcholine receptors are members of the ligand-gated ion channel receptor superfamily and may play important roles in modulating neurotransmission, cognition, sensory gating, and anxiety. Because of its distribution and abundance in the CNS, the α7 nicotinic receptor is a strong candidate to be involved in some of these functions. In this paper we describe the synthesis and in vitro profile of AR-R17779, (-)-spiro[1-azabicyclo[2.2.2]octane-3,5'oxazolidin-2'-one] (4a), a potent full agonist at the rat α7 nicotinic receptor, which is highly selective for the rat α7 nicotinic receptor over the α4β2 subtype. Preliminary SAR of AR-R17779 presented here indicate that there is little scope for modification of this rigid molecule as even minor changes result in significant loss of the α7 nicotinic receptor affinity.
