- Diastereoconvergent Synthesis of (–)-Paroxetine
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A diastereoconvergent approach to (–)-paroxetine from diastereomeric 3,4-epoxy-2-piperidones is reported. For this synthesis, a regioselective and stereodivergent CuI-catalyzed epoxide-ring-opening reaction of epoxyamide precursors to give the 4-(4-fluorophenyl)-2-piperidone skeleton with the correct absolute configuration is crucial. Using CuBr·SMe2 as a catalyst, the epoxide-ring-opening reaction takes place with inversion of configuration; the configuration is retained when CuI is used.
- Chamorro-Arenas, Delfino,Fuentes, Lilia,Quintero, Leticia,Cruz-Gregorio, Silvano,H?pfl, Herbert,Sartillo-Piscil, Fernando
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p. 4104 - 4110
(2017/08/07)
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- Structural determinants influencing the potency and selectivity of indazole-paroxetine hybrid G protein-coupled receptor kinase 2 inhibitors
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G protein-coupled receptor kinases (GRKs) phosphorylate activated receptors to promote arrestin binding, decoupling from heterotrimeric G proteins, and internalization. GRK2 and GRK5 are overexpressed in the failing heart and thus have become therapeutic
- Bouley, Renee,Waldschmidt, Helen V.,Cato, M. Claire,Cannavo, Alessandro,Song, Jianliang,Cheung, Joseph Y.,Yao, Xin-Qiu,Koch, Walter J.,Larsen, Scott D.,Tesmer, John J.G.
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supporting information
p. 707 - 717
(2017/11/23)
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- G PROTEIN-COUPLED RECEPTOR KINASE INHIBITORS AND METHODS FOR USE OF THE SAME
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Disclosed herein are novel GRK inhibitors and methods for their use in treating or preventing heart disease, such as cardiac failure, cardiac hypertrophy, and hypertension. In particular, disclosed herein are compounds of Formula (I) and pharmaceutically
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Paragraph 00144
(2017/04/04)
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- PAROXETINE DERIVATIVE
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A compound represented by Formula (1), or a pharmacologically acceptable salt thereof retains the principal therapeutic effect of paroxetine and has an improved CYP inhibitory effect: wherein R1 is a hydrogen atom or C1-6 alkyl group
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Paragraph 0117; 0118
(2013/08/14)
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- Enantioselective Michael additions to α,β-unsaturated imides catalyzed by a salen-al complex
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(Salen)aluminum complex 1b is an efficient catalyst for the conjugate addition of di- and trisubstituted nitriles to a wide range of acyclic alkyl- and aryl-substituted α,β-unsaturated imides. This new methodology provides access to multifunctional compounds that previously have not been readily accessible in enantioenriched form. Synthetic applications of these products include the preparation of enantiomerically enriched piperidines, as exemplified by an expedient asymmetric catalytic synthesis of (-)-paroxetine. Copyright
- Taylor, Mark S.,Jacobsen, Eric N.
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p. 11204 - 11205
(2007/10/03)
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- Synthesis of Enantiopure trans-3,4-Disubstituted Piperidines. An Enantiodivergent Synthesis of (+)- And (-)-Paroxetine
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Reaction of (R)-phenylglycinol with methyl 5-oxopentanoate gave either bicyclic lactam cis-1 (the kinetic product) or its isomer trans-1 (under equilibrating conditions) as the major products, which were converted to the corresponding (cis or trans) unsaturated lactams 4 and 5. On treatment with lithium alkyl (or aryl) cyanocuprates, these chiral building blocks undergo conjugate addition to give enantiopure trans-3,4-substituted 2-piperidone derivatives in high yield and stereoselectivity. The synthetic potential of this transformation is illustrated by the synthesis of (+)-femoxetine and the two enantiomers of the known antidepressant paroxetine.
- Amat, Mercedes,Bosch, Joan,Hidalgo, Jose,Canto, Margalida,Perez, Maria,Llor, Nuria,Molins, Elies,Miravitlles, Carles,Orozco, Modesto,Luque, Javier
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p. 3074 - 3084
(2007/10/03)
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- Improved synthesis of paroxetine hydrochloride propan-2-ol solvate through one of metabolites in humans, and characterization of the solvate crystals
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Paroxetine, a potent and selective inhibitor of 5-hydroxytryptamine (serotonin) uptake, was prepared through a piperidine derivative, which was reported to be one of the paroxetine metabolites in humans. Thus, the piperidine derivative was converted to its N-tert-butoxycarbonyl (N-Boc) derivative, which was then converted to N-Boc paroxetine. Paroxetine hydrochloride propan-2-ol (isopropyl alcohol (IPA)) solvate crystals were directly obtained from the N-Boc paroxetine by adding hydrogen chloride to the N-Boc paroxetine IPA solution. The amount of IPA content in the crystals was reduced by drying with a continuous change of powder X-ray diffraction patterns. Other characterizations of the solvate crystals were also conducted.
- Sugi, Kiyoshi,Itaya, Nobushige,Katsura, Tadashi,Igi, Masami,Yamazaki, Shigeya,Ishibashi, Taro,Yamaoka, Teiji,Kawada, Yoshihiro,Tagami, Yayoi,Otsuki, Michiya,Ohshima, Takao
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p. 529 - 536
(2007/10/03)
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- Piperidine derivative and process for preparing the same
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A piperidine derivative, which can be used as an intermediate for pharmaceuticals such as paroxetine useful as antidepressants, represented by the general formula (I): STR1 wherein R1 is hydrogen atom, benzyloxycarbonyl group or tert-butoxycarbonyl group; R2 is hydroxymethyl group, an alkylsulfonyloxymethyl group having an alkyl moiety of 1 to 2 carbon atoms, phenylsulfonyloxymethyl group which may have methyl group at the 4-position, (3,4-methylenedioxyphenyl)oxymethyl group, carboxyl group or --CO2 R7 group in which R7 is an alkyl group having 1 to 5 carbon atoms, and Z is methylene group or carbonyl group.
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