290296-68-3

Usage

Uses

Treatment of depression.

InChI:InChI=1/C29H29F6N3O2/c1-18-7-5-6-8-22(18)23-16-25(38-9-11-40-12-10-38)36-17-24(23)37(4)26(39)27(2,3)19-13-20(28(30,31)32)15-21(14-19)29(33,34)35/h5-8,13-17H,9-12H2,1-4H3

Upstream product

• 289686-69-7 2-(3,5-bis-trifluoromethyl-phenyl)-2-methyl-propionyl chloride 
• 290297-36-8 N-methyl-N-[6-(morpholin-4-yl)-4-(o-tolyl)pyridin-3-yl]amine 
• 328-70-1 3,6-bis(trifluoromethyl)bromobenzene 
• 67570-38-1 α,α-dimethyl-3,5-bis(trifluoromethyl)benzenemethanol 
• 290297-34-6 2,2-dimethyl-N-(6-morpholin-4-yl-4-o-tolyl-pyridin-3-yl)-propionamide 
• 58757-38-3 6-Chloronicotinoyl chloride 
• 290297-33-5 N-(4-iodo-6-morpholin-4-yl-pyridin-3-yl)-2,2-dimethyl-propionamide 
• 290297-32-4 2,2-dimethyl-N-(6-morpholin-4-yl-pyridin-3-yl)-propionamide 
• 70625-63-7 methyl 2-cyano-3-(2-methylphenyl)-2-propenoate 
• 529-20-4 2-methylphenyl aldehyde 
• 52023-68-4 6-(morpholin-4-yl)pyridin-3-amine 
• 873443-68-6 2-chloro-3-cyano-4-(2-methylphenyl)-6-(4-morpholinyl)pyridine 
• 26820-62-2 4-(5-nitro-pyridin-2-yl)-morpholine 
• 873443-66-4 3-cyano-2,6-dichloro-4-(2-methylphenyl)pyridine 

Relevant academic research and scientific papers

Efficient synthesis of novel NK1 receptor antagonists: Selective 1,4-addition of Grignard reagents to 6-chloronicotinic acid derivatives

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.

Research and development of an efficient process for the construction of the 2,4,5-substituted pyridines of NK-1 receptor antagonists

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.

Use of NK-1 receptor antagonists against benign prostatic hyperplasia

The invention relates to the use of an NK-1 receptor antagonist for the treatment or prevention of benign prostatic hyperplasia (BPH). The preferred NK-1 receptor antagonists are compounds of the general formula wherein the meanings of R, R1, R2, R2′, R3, R4 are explained in the specification and the pharmaceutically acceptable acid addition salts and the prodrugs thereof Preferred compounds are 2-(3,5-bis-trifluoromethyl-phenyl)-N-methyl-N-(6-morpholin-4-yl-4-o-tolyl-pyridin-3-yl)-isobutyramide, 2-(3,5-bis-trifluoromethyl-phenyl)-N-methyl-N-[6-(4-methyl-piperazin-1-yl)-4-o-tolyl-pyridin-3-yl]-isobutyramide, 2-(3,5-bis-trifluoromethyl-phenyl)-N-[6-(1,1-dioxo-1λ6-thiomorpholin-4-yl)-4-o-tolyl-pyridin-3-yl]-N-methyl-isobutyramide and 2-(3,5-bis-trifluoromethyl-phenyl)-N-[6-(1,1-dioxo-1λ6-thiomorpholin-4-yl)-4-(4-fluoro-2-methyl-phenyl)-pyridin-3-yl]-N-methyl-isobutyramide. The invention also relates to pharmaceutical composition comprising one or more such NK-1 receptor antagonists and a pharmaceutically acceptable excipient for the treatment and/or prevention of benign prostatic hyperplasia.

Method of treatment and/or prevention of brain, spinal or nerve injury

The invention relates to a method of treatment and/or prevention of brain, spinal or nerve injury comprising administration to a person in need of such treatment, of a therapeutically effective amount of an NK-1 receptor antagonist compound of the formula wherein the meanings of R, R1, R2, R2', R3, R4 are explained in the specification and the pharmaceutically acceptable acid addition salts and the prodrugs thereof either alone or in combination with a magnesium salt. Exemplified is the use of N-(3,5-bis-trifluoromethyl-benzyl)-N-methyl-6-(4-methyl-piperazin-1-yl)-4-o-tolyl-nicotinamide. The invention also relates to pharmaceutical composition comprising one or more such NK-1 receptor antagonists, optionally in combination with a magnesium salt, and a pharmaceutically acceptable excipient for the treatment and/or prevention of brain, spinal or nerve injury.

Substituted 4-phenyl-pyridine compounds with activity as antagonists of neurokinin 1 receptors

Substituted 4-phenyl-pyridine compounds with activity as antagonists of Neurokinin 1 receptors, methods of making these compounds and preparing.

NK-1 receptor active amine oxide prodrugs

Compounds of the invention are amine oxide prodrugs showing activity on the NK1 receptor.

4-phenyl-pyridine derivatives

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.

2-(3,5-Bis-trifluoromethyl-phenyl)-N-methyl-N-(6-morpholin-4-yl-4-o-tolyl-pyridin-3-yl)-isobutyramide

The invention relates to the compound of the formula which is 2-(3,5-bis-trifluoromethyl-phenyl)-N-methyl-N-(6-morpholin-4-yl-4-o-tolylpyridin-3-yl)-isobutyramide. It has been found that this compound has a high affinity to the NK-1 receptor and it is the