- NK1 receptor-targeting antagonist and application of same to chemotherapy-induced nausea and vomiting
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The invention relates to a NK1 receptor-targeting antagonist and application of the same to chemotherapy-induced nausea and vomiting, belonging to the technical field of adjuvant therapeutics for tumor chemotherapy. The invention provides a compound as shown in a formula I which is described in the specification, or a racemate, stereoisomer, tautomer, isotopic label, oxynitride or pharmaceutically-acceptable salt thereof. The invention also provides a preparation method for the compound, a pharmaceutical compositions and the application of the compound or the racemate, stereoisomer, tautomer,isotopic label, oxynitride or pharmaceutically-acceptable salt thereof.
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- 4-(5-(2-(3,5-bis(trifluoromethyl)phenyl)-N,2-dimethylpropanamido)-4-(o-tolyl)pyridin-2-yl)-1-methyl-1-((phosphonooxy)methyl)piperazin-1-ium as a neurokinin receptor modulator
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Compounds and methods for the prevention and/or treatment of diseases which are pathophysiologically mediated by the neurokinin (NK1) receptor, based on 4-(5-(2-(3,5-bis(trifluoromethyl)phenyl)-N,2-dimethylpropanamido)-4-(o-tolyl)3yridine-2-yl)-1-methyl-1-((phosphonooxy)methyl)piperazin-1-ium and pharmaceutically acceptable salts thereof.
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Page/Page column 31
(2016/08/29)
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- METHODS OF MAKING NETUPITANT AND INTERMEDIATES THEREOF
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Methods are disclosed for the preparation of netupitant and pharmaceutically acceptable salts thereof which are novel, easily reproducible, environmentally safe and cost effective. The methods may employ inexpensive starting materials and the preparation processes for intermediates are simple and highly reproducible. Novel intermediates for the preparation of netupitant and pharmaceutically acceptable salts thereof are also disclosed. Amorphous netupitant and methods of making same are disclosed.
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- SUBSTITUTED 4-PHENYL-PYRIDINES FOR TREATMENT OF NK-1 RECEPTOR RELATED DISEASES
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PROBLEM TO BE SOLVED: To provide new derivatives of 4-phenyl-pyridine compounds that are effective NK1 receptor antagonists, with enhanced physicochemical and/or biological properties, and methods for producing the 4-phenyl-pyridine compounds. SOLUTION: Disclosed are compounds, compositions and methods for the prevention and/or treatment of diseases which are pathophysiologically mediated by the neurokinin (NKj) receptor. The compounds have the general formula (I). COPYRIGHT: (C)2015,JPOandINPIT
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- Substituted 4-phenyl pyridines having anti-emetic effect
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Disclosed are compounds, compositions and methods for the prevention and/or treatment of diseases which are pathophysiologically mediated by the neurokinin (NK1) receptor. The compounds have the general formula (I):
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- Design and synthesis of a novel, achiral class of highly potent and selective, orally active neurokinin-1 receptor antagonists
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The discovery of a novel, achiral pyridine class of potent and orally active neurokinin-1 (NK1) receptor antagonists is described. The evaluation of this class is briefly outlined, leading to the identification of netupitant 21 and befetupitant 29, two new proprietary chemical entities with high affinity and excellent CNS penetration.
- Hoffmann, Torsten,Boes, Michael,Stadler, Heinz,Schnider, Patrick,Hunkeler, Walter,Godel, Thierry,Galley, Guido,Ballard, Theresa M.,Higgins, Guy A.,Poli, Sonia M.,Sleight, Andrew J.
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p. 1362 - 1365
(2007/10/03)
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- Research and development of an efficient process for the construction of the 2,4,5-substituted pyridines of NK-1 receptor antagonists
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Roche has identified a 2,4,5-trisubstituted pyridine template for a new class of potent NK1 receptor antagonists. Previous strategies for construction of the pyridine core of these NK-1 receptor antagonists involved functionalization of a 2,5-disubstituted pyridine. We now report on construction of the pyridine core from commodity components. Shestopalov reported the synthesis of trans-4′-aryl-5′-cyano-1′,2′,3′, 4′-tetrahydro-6′-hydroxy-2′-oxo-1,3′-bipyridinium inner salts from 1-(2-amino-2-oxo-ethyl)pyridinium chloride, aromatic aldehydes, and ethyl cyanoacetate in the presence of a base. Reaction of these salts with phosphorus oxychloride affords 4-aryl-3-cyano-2,6-dichloropyridines. These are efficiently converted to nicotinamide precursors of the Roche NK-1 receptor antagonists by regioselective displacement of one chlorine by an amine, hydrogenolysis of the remaining chlorine, and nitrile hydrolysis.
- Harrington, Peter J.,Johnston, Dave,Moorlag, Henk,Wong, Jim-Wah,Hodges, L. Mark,Harris, Les,McEwen, Gerald K.,Smallwood, Blair
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p. 1157 - 1166
(2012/12/23)
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- Efficient synthesis of novel NK1 receptor antagonists: Selective 1,4-addition of Grignard reagents to 6-chloronicotinic acid derivatives
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A new efficient synthesis of two novel classes of NK1 receptor antagonists, among them befetupitant and netupitant, starting from 6-chloronicotinic acid is described. The introduction of the o-tolyl substituent at C(4) of the pyridine ring was achieved by a one-pot selective 1,4-Grignard addition/oxidation sequence to 6-chloronicotinic acid or a derivative of it. The scope of this addition/oxidation sequence was examined. It was also shown that the carboxylic function can be converted to a methyl amino group by a Hofmann rearrangement followed by reduction. Furthermore, a new high-yielding synthesis of 2-(3,5-bistrifluoromethylphenyl)-2-methyl propionic acid based on the carbonylation of the tertiary alcohol obtained by Grignard addition of 3,5-bis(trifluoromethyl)bromobenzene to acetone was established.
- Hoffmann-Emery, Fabienne,Hilpert, Hans,Scalone, Michelangelo,Waldmeier, Pius
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p. 2000 - 2008
(2007/10/03)
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- 4-phenyl-pyridine derivatives
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The compounds of the related invention are related to 4-phenyl-pyridine derivatives connected by a bridge containing oxygen or nitrogen to a phenyl derivative.
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