- Synthesis and Pharmacological Evaluation of Novel Pyrazolyl Piperidine Derivatives as Effective Antiplatelet Agents
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The synthesis and antiplatelet activity of substituted pyrazolyl piperidine derivatives (3a–n) are described. These compounds were synthesized by an improved ring opening reaction of 2-arylidene quinuclidinone using hydrazine hydrate under mild conditions
- Soni, Jigar Y.,Tamboli, Riyaj S.,Giridhar, Rajani,Yadav, Mange Ram,Thakore, Sonal
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p. 1279 - 1286
(2017/03/27)
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- Novel 2-(substituted benzyl)quinuclidines inhibit human α7 and α4β2 nicotinic receptors by different mechanisms
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This work presents the design and synthesis of a series of novel 2-benzylquinuclidine derivatives, comprising 12 methiodide and 11 hydrochloride salts, and their structural and pharmacological characterization at the human (h) α7 and α4β2 nicotinic receptors (nAChRs). The antagonistic potency of these compounds was tested by Ca2+ influx assays on cells expressing the hα7 or hα4β2 nAChR subtype. To determine the inhibitory mechanisms, additional radioligand binding experiments were performed. The results indicate that the methiodides present the highest affinities for the hα7 nAChR agonist sites, while the same compounds bind preferably to the hα4β2 nAChR ion channel domain. These results indicate that the methiodides are competitive antagonists of the hα7 nAChR but noncompetitive antagonists of the hα4β2 subtype. Docking and molecular dynamics simulations showed that the methiodide derivative 8d binds to the hα7 orthosteric binding sites by forming stable cation-π interactions between the quaternized quinulinuim moiety and the aromatic box in the receptor, whereas compounds 7j and 8j block the hα4β2 AChR ion channel by interacting with a luminal domain formed between the serine (position 6′) and valine (position 13′) rings that overlaps the imipramine binding site.
- Arias, Hugo R.,López, Jhon J.,Feuerbach, Dominik,Fierro, Angélica,Ortells, Marcelo O.,Pérez, Edwin G.
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p. 2420 - 2430
(2013/10/01)
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- 2-(Arylmethyl)-3-substituted quinuclidines as selective α7 nicotinic receptor ligands
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A series of 2-(arylmethyl)-3-substituted quinuclidines was developed as α7 neuronal nicotinic acetylcholine receptor (nAChR) agonists based on a putative pharmacophore model. The series is highly selective for the α7 over other nAChRs (e.g., the α4β2 of the CNS, and the muscle and ganglionic subtypes) and is functionally tunable at α7. One member of the series, (+)-N-(1-azabicyclo[2.2.2]oct-3-yl)benzo[b]furan-2-carboxamide (+)-8l), has potent agonistic activity for the α7 nAChR (EC50 = 33 nM, Imax = 1.0), at concentrations below those that result in desensitization.
- Mazurov, Anatoly,Klucik, Jozef,Miao, Lan,Phillips, Teresa Y.,Seamans, Angela,Schmitt, Jeffrey D.,Hauser, Terry A.,Johnson Jr., Raymond T.,Miller, Craig
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p. 2073 - 2077
(2007/10/03)
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