165110-20-3Relevant articles and documents
GLYCOSIDASE INHIBITORS
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Page/Page column 100, (2014/10/15)
Compounds of formula (I) wherein X1, X2, W, R1 to R5, L and m have the meaning according to the claims, are glucosidase inhibitors, and can be employed, inter alia, for the treatment of Alzheimer's disease.
Controlling chemoselective transformations of 4-acylpyridines via a Pd-C catalytic hydrodechlorination-hydrogenation
Cheng, Chuanjie,Wang, Bo,Liu, Nan,Chen, Wenwen,Wang, Xinyan,Hu, Yuefei
, p. 930 - 935 (2014/01/23)
A novel Pd-C catalytic hydrodechlorination-hydrogenation was developed for a multi-step one-pot transformation of 4-acylpyridines. Under the selected conditions, 4-benzoylpyridines and 4-alkanoylpyridines were chemoselectively converted into the corresponding 4-benzylpiperidine hydrochlorides and α-alkyl-4-piperidinemethanol hydrochlorides, respectively. This catalytic method was performed simply by an addition of 1 equiv of ClCH 2CHCl2 to the conventional hydrogenation system and directly gave the crystalline piperidine hydrochlorides in practical quantitative yields.
Convenient, benign and scalable synthesis of 2- and 4-substituted benzylpiperidines
Agai, Bela,Proszenyak, Agnes,Tarkanyi, Gabor,Vida, Laszlo,Faigl, Ferenc
, p. 3623 - 3632 (2007/10/03)
A short, scalable and environmentally benign synthesis of 2- and 4-substituted benzylpiperidines has been developed. The method is based on the temperature-programmed consecutive deoxygenation and heteroaromatic ring saturation of aryl(pyridin-2-yl)- and aryl(pyridin-4-yl)methanols and aryl(pyridin-4-yl)methanones in the presence of Pd/C catalyst. The crucial roles of the temperature, the acidity and the substrate structure in the change of selectivity have been demonstrated by isolation of several substituted aryl(piperidine)methanols. The carbinols and ketones were prepared from commercially available pyridinecarbaldehydes or 4-cyanopyridine and substituted bromobenzenes via organometallic intermediates. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.
4-substituted piperidine analogs and their use as subtype selective NMDA receptor antagonists
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, (2011/05/18)
PCT No. PCT/US96/20872 Sec. 371 Date Sep. 16, 1998 Sec. 102(e) Date Sep. 16, 1998 PCT Filed Dec. 20, 1996 PCT Pub. No. WO97/23216 PCT Pub. Date Jul. 3, 1997Novel 4-substituted piperidine analogs, pharmaceutical compositions containing the same and the method of using 4-substituted piperidine analogs are selective active antagonists of N-methyl-D-aspartate (NMDA) receptor subtypes for treating conditions such as stroke, cerebral ischemia, central nervous system trauma, hypoglycemia, psychosis, anxiety, migraine headaches, glaucoma, CMV retinitis, aminoglycoside antibiotics-induced hearing loss, convulsions, chronic pain, opioid tolerance or withdrawal, urinary incontinence or neurodegenerative disorders, such as lathyrism, Alzheimer's Disease, Parkinsonism and Huntington's Disease are described.
4-hydroxy-1-[2-(4-hydroxyphenoxy)ethyl]-4-(4-methylbenzyl)piperidine: A novel, potent, and selective NR1/2B NMDA receptor antagonist
Zhou, Zhang-Lin,Cai, Sui Xiong,Whittemore, Edward R.,Konkoy, Christopher S.,Espitia, Stephen A.,Tran, Minhtam,Rock, David M.,Coughenour, Linda L.,Hawkinson, Jon E.,Boxer, Peter A.,Bigge, Christopher F.,Wise, Lawrence D.,Weber, Eckard,Woodward, Richard M.,Keana, John F. W.
, p. 2993 - 3000 (2007/10/03)
A structure-based search and screen of our compound library identified N-(2-phenoxyethyl)4-benzylpiperidine (8) as a novel N-methyl-D-aspartate (NMDA) receptor antagonist that has high selectivity for the NR1/2B subunit combination (IC50 = 0.63 μM). We report on the optimization of this lead compound in terms of potency, side effect liability, and in vivo activity. Potency was assayed by electrical recordings in Xenopus oocytes expressing cloned rat NMDA receptors. Side effect liability was assessed by measuring affinity for α1-adrenergic receptors and inhibition of neuronal K+ channels. Central bioavailability was gauged indirectly by determining anticonvulsant activity in a mouse maximal electroshock (MES) assay. Making progressive modifications to 8, a hydroxyl substituent on the phenyl ring para to the oxyethyl tether (10a) resulted in a ~25-fold increase in NR1A/2B potency (IC50 = 0.025 μM). p-Methyl substitution on the benzyl ring (10b) produced a ~3-fold increase in MES activity (ED50 = 0.7 mg/kg iv). Introduction of a second hydroxyl group into the C-4 position on the piperidine ring (10e) resulted in a substantial decrease in affinity for α1 receptors and reduction in inhibition of K+ channels with only a modest decrease in NR1A/2B and MES potencies. Among the compounds described, 10e (4- hydroxy-N-[2-(4-hydroxyphenoxy)ethyl]-4-(4-methylbenzyl)piperidine, Co 101244/PD 174494) had the optimum pharmacological profile and was selected for further biological evaluation.
