ChemInform Abstract: (S)‐(‐)‐5‐Ethynyl‐3‐(1‐methyl‐2‐pyrrolidinyl)pyridine Maleate (SIB‐ 1508Y): A Novel Anti‐Parkinsonian Agent with Selectivity for Neuronal Nicotinic Acetylcholine Receptors.

Abstract

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Chemistry and Pharmacology of a Series of Unichiral Analogues of 2-(2-Pyrrolidinyl)-1,4-benzodioxane, Prolinol Phenyl Ether, and Prolinol 3-Pyridyl Ether Designed as α4β2-Nicotinic Acetylcholine Receptor Agonists

“…TLC analyses were carried out on alumina sheets precoated with silica gel 60 F254 and visualized with UV light; R f values are given for guidance. 1 H and 13 C NMR spectra were recorded at 300 and 75 MHz using an FT-NMR spectrometer. Chemical shifts are reported in ppm relative to residual solvent (CHCl 3 , MeOH, or DMSO) as internal standard.…”

“…The S isomer of 18 was obtained by treatment of (S)-N-Boc-2-hydroxymethylazetidine with PPh 3 (1.2 mol), DIAD (1.2 mol), and equimolar 3-benzyloxyphenol. The R,S 13 C NMR (CDCl 3 ) δ 23.2, 28.9, 41.9, 55.8, 57.9, 64.5, 73.0, 106.9, 136.2, 144.8, 145.5, 155.9.…”

“…1 H NMR and 13 C NMR spectra and elemental analysis results for the final compounds 4−13, 4a−7a, 9a, 11a, and 12a; 1 H NMR spectra of the R,S and S,S diastereomers of the intermediates 24, 27, and 28; and the DSC trace of (S,S)-24 (PDF) Molecular formula strings (CSV)…”

α6β2* and α4β2* Nicotinic Acetylcholine Receptors As Drug Targets for Parkinson's Disease

“…Numerous other drugs in the literature have also been reported to interact with ␣4␤2* nAChRs, including undesignated compounds from Abbott Laboratories (Abbott Park, IL), Targacept, Inc. (WinstonSalem, NC), SIBIA Neurosciences (La Jolla, CA), and University of Bath (Bath, UK). However, at this point, their selectivity is uncertain because their interaction with ␣6␤2* nAChRs and/or other nAChR subtypes is not known (Bencherif et al, 1996;Cosford et al, 1996;DonnellyRoberts et al, 1996DonnellyRoberts et al, , 1998Bencherif et al, 2000;Sharples 944 et al, 2000;Buccafusco et al, 2005;Gotti et al, 2006b;Lippiello et al, 2006;Wang et al, 2006;Dwoskin and Bardo, 2009). All together, these observations indicate that the majority of available ␣4␤2* nAChR drugs may interact with other nAChR subtypes, notably ␣6␤2* nAChRs; at best these agents should be regarded as only ␤2-selective.…”

Recent Developments in Novel Antidepressants Targeting α4β2-Nicotinic Acetylcholine Receptors

“…SIB-1508Y (33) 148 is a selective α4β2-nAChR partial agonist (EC 50 = 1.8 μM; efficacy = 49% relative to that of compound 10), having no activity at homomeric α7or muscle-type α1β1γδ- nAChRs and weak activity at ganglionic α3β4-nAChRs (EC 50 = 23 μM; efficacy = 52% relative to that of compound 10). 148 In vitro, compound 33 stimulated dopamine release from slices of rat striatum prepared from various brain regions, and the effect was blocked by nAChR antagonists compound 1 or compound 18. 149 On the other hand, compound 33 was found to show relatively weak effects on NE or 5-HT release.…”