220143-50-0

Upstream product

• 612-60-2 7-methylquinoline 
• 7677-24-9 trimethylsilyl cyanide 
• 4053-43-4 7-methylquinoline N-oxide 

Downstream Products

• 1432731-44-6 4-(4-fluorophenyl)-7-(((2S)-2-methyl-5-(trifluoromethyl)piperazin-1-yl)methyl)quinolin-2-carbonitrile 
• 1432729-24-2 4-(4-fluorophenyl)-7-(((2S)-2-methyl-(5R)-5-(trifluoromethyl)piperazin-1-yl)methyl)quinoline-2-carboxamide 
• 1432729-25-3 4-(4-fluorophenyl)-7-(((2S)-2-methyl-(5S)-5-(trifluoromethyl)piperazin-1-yl)methyl)quinoline-2-carboxamide 
• 1432731-45-7 7-(dibromomethyl)-4-(4-fluorophenyl)quinoline-2-carbonitrile 
• 1432731-46-8 4-(4-fluorophenyl)-7-formylquinoline-2-carboxamide 
• 1432731-47-9 2-(aminocarbonyl)-4-(4-fluorophenyl)quinoline-7-carboxylic acid 
• 1432730-33-0 4-(4-fluorophenyl)-7-(pyrrolidin-1-ylcarbonyl)quinoline-2-carboxamide 
• 1432730-37-4 4-(4-fluorophenyl)-7-(pyrimidin-5-ylmethyl)quinoline-2-carboxamide 
• 932369-61-4 4-(4-fluorophenyl)-7-methylquinoline-2-carbonitrile 
• 1432728-25-0 4-(4-fluorophenyl)-7-methylquinoline-2-carboxamide 
• 1432730-82-9 7-[2-(6-chloropyridin-3-yl)-(1R)-1-hydroxyethyl]-4-(4-fluorophenyl)quinoline-2-carboxamide 
• 1432730-83-0 7-[2-(6-chloropyridin-3-yl)-(1S)-1-hydroxyethyl]-4-(4-fluorophenyl)quinoline-2-carboxamide 
• 1432730-84-1 7-[2-(6-chloropyridin-3-yl)-1-hydroxyethyl]-4-(4-fluorophenyl)quinoline-2-carboxamide 
• 179380-98-4 7-(bromomethyl)-4-(4-fluorophenyl)quinoline-2-carbonitrile 

Relevant academic research and scientific papers

Discovery of 4-arylquinoline-2-carboxamides, highly potent and selective class of mGluR2 negative allosteric modulators: From HTS to activity in animal models

Antagonism of the mGluR2 receptor has the potential to provide therapeutic benefit to cognitive disorders by elevating synaptic glutamate, the primary excitatory neurotransmitter in the brain. Selective antagonism of the mGluR2 receptor, however, has so far been elusive, given the very high homology of this receptor with mGluR3, particularly at the orthosteric binding site. Given that inhibition of mGluR3 has been implicated in undesired effects, we sought to identify selective mGluR2 negative allosteric modulators. Herein we describe the discovery of the highly potent and selective class of mGluR2 negative allosteric modulators, 4-arylquinoline-2-carboxamides, following a successful HTS campaign and medicinal chemistry optimization, showing potent in vivo efficacy in rodent.

PRMT5 INHIBITOR COMPOUNDS

A series of PRMT5 inhibitor compounds are described. The compounds are useful as PRMT5 inhibitor compounds and in the treatment of PRMT5 mediated diseases, disorders, and symptoms thereof.

Synthesis and Preliminary Studies of a Novel Negative Allosteric Modulator, 7-((2,5-Dioxopyrrolidin-1-yl)methyl)-4-(2-fluoro-4-[11C]methoxyphenyl) quinoline-2-carboxamide, for Imaging of Metabotropic Glutamate Receptor 2

Metabotropic glutamate 2 receptors (mGlu2) are involved in the pathogenesis of several CNS disorders and neurodegenerative diseases. Pharmacological modulation of this target represents a potential disease-modifying approach for the treatment of substance abuse, depression, schizophrenia, and dementias. While quantification of mGlu2 receptors in the living brain by positron emission tomography (PET) would help us better understand signaling pathways relevant to these conditions, few successful examples have been demonstrated to image mGlu2 in vivo, and a suitable PET tracer is yet to be identified. Herein we report the design and synthesis of a radiolabeled negative allosteric modulator (NAM) for mGlu2 PET tracer development based on a quinoline 2-carboxamide scaffold. The most promising candidate, 7-((2,5-dioxopyrrolidin-1-yl)methyl)-4-(2-fluoro-4-[11C]methoxyphenyl) quinoline-2-carboxamide ([11C]QCA) was prepared in 13% radiochemical yield (non-decay-corrected at the end of synthesis) with >99% radiochemical purity and >74 GBq/μmol (2 Ci/μmol) specific activity. While the tracer showed limited brain uptake (0.3 SUV), probably attributable to effects on PgP/Bcrp efflux pump, in vitro autoradiography studies demonstrated heterogeneous brain distribution and specific binding. Thus, [11C]QCA is a chemical probe that provides the basis for the development of a new generation mGlu2 PET tracers.

C?H Cyanation of 6-Ring N-Containing Heteroaromatics

Heteroaromatic nitriles are important compounds in drug discovery, both for their prevalence in the clinic and due to the diverse range of transformations they can undergo. As such, efficient and reliable methods to access them have the potential for far-reaching impact across synthetic chemistry and the biomedical sciences. Herein, we report an approach to heteroaromatic C?H cyanation through triflic anhydride activation, nucleophilic addition of cyanide, followed by elimination of trifluoromethanesulfinate to regenerate the cyanated heteroaromatic ring. This one-pot protocol is simple to perform, is applicable to a broad range of decorated 6-ring N-containing heterocycles, and has been shown to be suitable for late-stage functionalization of complex drug-like architectures.

Regioselective direct oxidative C-H cyanation of quinoline and its derivatives catalyzed by vanadium-containing heteropoly acids

A direct oxidative C-H cyanation of quinoline and its derivatives using trimethylsilyl cyanide as the cyano source and molecular oxygen as the terminal oxidant has been developed. In the presence of catalytic amounts of vanadium-containing heteropoly acids, e.g., H7PV4Mo8O40, cyanation of various quinoline and its derivatives preferentially took place at the 4-position, affording the corresponding substituted 4-cyanoquinolines as the major products.

QUINOLINE CARBOXAMIDE AND QUINOLINE CARBONITRILE DERIVATIVES AS mGluR2-NEGATIVE ALLOSTERIC MODULATORS, COMPOSITIONS, AND THEIR USE

The present invention provides quinoline carboxamide and quinoline carbonitrile compounds of formula (I) wherein ring A, RQ, -L-, R1, n, R2, and R3 are as defined herein. The compounds of the invention are useful as non-competitive mGluR2 antagonists, or mGluR2 negative allosteric modulators (NAMs), and in methods of treating a patient (preferably a human) for diseases or disorders in which the mGluR2-NAM receptor is involved, such as Alzheimer's disease, cognitive impairment, schizophrenia and other mood disorders, pain disorders and sleep disorders, by administering to the patient a therapeutically effective amount of a compound of the invention, or a pharmaceutically acceptable salt thereof. The invention is also directed to pharmaceutical compositions comprising a compound of the invention, or a pharmaceutically acceptable salt thereof, (optionally in combination with one or more additional active ingredients), and a pharmaceutically acceptable carrier, and the use of the compounds and pharmaceutical compositions of the invention in the treatment of such diseases.

Novel pharmaceutical compounds

The instant invention provides compounds of Formula I which are leukotriene biosynthesis inhibitors. Compounds of Formula I are useful as anti-atherosclerotic, anti-asthmatic, anti-allergic, anti-inflammatory and cytoprotective agents.

Polycyclic N-heterocyclic compounds. Part 52. One-step syntheses of imidazo[1,5-a]pyridines, imidazo[1,5-a]quinolines and imidazo[5,1-a]isoquinolines by Vilsmeier reactions of pyridine-2-carbonitriles, quinoline-2-carbonitriles and isoquinoline-1-carbonitriles

The versatile, one-step synthesis of imidazo[1,5-a]pyridines by the reaction of pyridine-2-carbonitriles with DMF under Vilsmeier conditions is described. This reaction was applied to the syntheses of imidazo[1,5-a]quinolines from quinoline-2-carbonitriles, and of imidazo[5,1-a]isoquinolines from isoquinoline-1-carbonitriles.