(<i>S</i>)-(−)-5-Ethynyl-3-(1-methyl-2-pyrroli- dinyl)pyridine Maleate (SIB-1508Y):  A Novel Anti-Parkinsonian Agent with Selectivity for Neuronal Nicotinic Acetylcholine Receptors

Cosford, Nicholas D. P.; Bleicher, Leo S.; Herbaut, A.; Mccallum, J. S.; Vernier, Jean‐Michel; Dawson, Harry Medforth; Whitten, Jeffrey P.; Adams, P; Chavez-Noriega, Laura E.; Correa, Lucia; Crona, James H.; Mahaffy, L. S.; Menzaghi, Frédérique; Rao, Tadimeti S.; Reid, Richard T.; Sacaan, Aida; Santori, Emily M.; Stauderman, Kenneth A.; Whelan, Kevin; Lloyd, G. Kenneth; McDonald, Ian A.

doi:10.1021/jm960328w

Cited by 93 publications

(53 citation statements)

References 19 publications

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“…Nicotine analogues. a The IC 50 value express inhibition of [ 3 H]-nicotine binding in rat cortex (IC 50 (nicotine) = 4 nM) [26]. b The K i values express inhibition of [ 3 H]-nicotine binding in rat brain (K i ((R/S)-nicotine) = 3 nM) [27].…”

Section: Nicotinoidsmentioning

confidence: 99%

“…In the case of nicotine, the (S)-enantiomer possess a 10-100 times higher affinity than the (R)-enantiomer [3,4,27], and for SIB-1508Y, the (S)-enantiomer displays a 25 times higher affinity [26].…”

Section: Nicotine Derivativesmentioning

confidence: 99%

“…(3)) [24]. Due to the large number of nicotine analogues prepared, the SAR of nicotine has been well established (Table 1) [25][26][27][28]. In addition to nicotine (see previous section), the pharmacology of SIB-1508Y has been thoroughly evaluated [26].…”

Section: Nicotine Derivativesmentioning

confidence: 99%

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Agonists at the a4b2 Nicotinic Acetylcholine Receptors Relationships and Molecular Modelling

Je¹,

2001

CMC

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Agonists of the alpha4beta2 nicotinic acetylcholine receptors have been synthesised as potential drugs for treatment of a variety of diseases. In this review, the published nicotinic agonists are presented and, on the basis of the molecular structure, the compounds are divided into three compound classes, nicotinoids (structurally close to nicotine), bicyclic compounds (structurally close to epibatidine and anatoxin-a), and analogues of imidacloprid (structurally close to the insecticide imidacloprid). The structure-activity relationships are discussed within and in between the classes. On the basis of computational studies of ligands for the nicotinic acetylcholine receptors the structure-activity relationships are discussed and a possible binding mode suggested. The binding mode encompasses: (A) an interaction between an anionic site in the receptor and the protonated nitrogen atom in the ligand, (B) a hydrogen bond between a hydrogen bond donor in the receptor and a hydrogen bond acceptor in the ligand, (C) an interaction between a pi-system (heteroaromatic ring, carbonyl bond) in the ligand and another pi-system or a positively charged amino acid residue in the binding site, (D) a pi-cation interaction between aromatic residues in the receptor binding site and the protonated nitrogen atom in the ligand, and (E) steric interactions of positive and negative character around the aliphatic and the heteroaromatic part of the ligand.

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Section: Nicotinoidsmentioning

confidence: 99%

Section: Nicotine Derivativesmentioning

confidence: 99%

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Agonists at the a4b2 Nicotinic Acetylcholine Receptors Relationships and Molecular Modelling

Je¹,

2001

CMC

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“…Murphy et al (31) applied the Ir-catalyzed borylation and Cu-catalyzed halogenations sequence in one pot for the meta-bromination of nicotine which can be converted to altinicline (tested for the treatment of Parkinson's disease) over two steps with 89% yield (Scheme 72) (143). Whereas earlier synthesis of altinicline involved five-step with overall yield 32% (144).…”

Section: Applications In Total Synthesis and Drug Discoverymentioning

confidence: 99%

Distant C-H Activation/Functionalization: A New Horizon of Selectivity Beyond Proximity

et al. 2015

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Activation/functionalization of inert C-H bond has undergone rapid growth in last decade and provides novel retro-synthetic disconnections for the synthesis of valuable molecules. The selectivity is often achieved by the use of directing group and is mainly limited to the proximal C-H bond. Initially, meta C-H activations were based on electronic or steric control and now it can be achieved by employing nitrile-based end-on-template as the directing group. The compilation of the remote C-H activation strategy will provide the useful linkage to the scientific community. This article is focused on recent progress in remote C-H activation, mechanistic understanding, and its applications in the field of total synthesis of targeted molecules.

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“…[1][2][3][4][5][6] There are data on the use of α-arylpyrrolidines as chiral catalysts 7 and organocatalysts. [8][9][10] Particular attention is devoted to the α-arylpyrrolidines containing carboxamide substituent at nitrogen atom.…”

Section: Introductionmentioning

confidence: 99%

New method of synthesis of 2-arylpyrrolidines: reaction of resorcinol and its derivatives with γ-ureidoacetals

Газизов¹,

Smolobochkin²,

Voronina³

et al. 2014

Arkivoc

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(S)-(−)-5-Ethynyl-3-(1-methyl-2-pyrroli- dinyl)pyridine Maleate (SIB-1508Y): A Novel Anti-Parkinsonian Agent with Selectivity for Neuronal Nicotinic Acetylcholine Receptors

Cited by 93 publications

References 19 publications

Agonists at the a4b2 Nicotinic Acetylcholine Receptors Relationships and Molecular Modelling

Agonists at the a4b2 Nicotinic Acetylcholine Receptors Relationships and Molecular Modelling

Distant C-H Activation/Functionalization: A New Horizon of Selectivity Beyond Proximity

New method of synthesis of 2-arylpyrrolidines: reaction of resorcinol and its derivatives with γ-ureidoacetals

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