217448-53-8

Usage

Structure

Brominated derivative of 2(1H)-pyridinone with a benzyl group attached to the nitrogen atom

Potential applications

Organic synthesis and pharmaceutical research

Use as a building block

Synthesis of various biologically active compounds, development of new pharmaceuticals

Reactivity and properties

Influenced by the bromine substituent, useful in the design and study of new chemical reactions and processes

Value in science

Diverse potential applications in chemistry and pharmaceutical science

Upstream product

• 2589-31-3 N-benzylpyridinium bromide 
• 13466-38-1 5-bromopyridin-2(1H)-one 
• 100-39-0 benzyl bromide 
• 100-44-7 benzyl chloride 
• 1753-62-4 N-benzyl-2-pyridone 
• 13466-38-1 5-bromopyridin-2-ol 
• 100-51-6 benzyl alcohol 

Downstream Products

• 1594127-49-7 1-benzyl-5-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2-dihydropyridin-2(1H)-one 
• 92444-98-9 1-benzyl-5-methylpyridin-2(1H)-one 
• 1616400-79-3 C₁₅H₁₂N₂OS 

Relevant academic research and scientific papers

Regioselective N-Functionalization of Tautomerizable Heterocycles through Methyl Trifluoromethanesulfonate-Catalyzed Substitution of Alcohols and Alkyl Group Migrations

A catalytic synthetic strategy has been developed combining two protocols, such as, direct nucleophilic substitution of alcohols followed by X- to N- alkyl group migration (X=O, S) to access N-functionalized benzoxazolones, benzothiazolethiones, indolinone, benzoimidazolethiones, and pyridinones derivatives. Methyl trifluoromethanesulfonate (MeOTf) was found to catalyze the reaction, which revealed the catalytic property of MeOTf. A mechanism was established through experiments as well as DFT calculations wherein the ?OH group of alcohols were converted to the corresponding ?OMe groups and in situ generated TfOH. The ?OMe groups produced underwent TfOH catalyzed ?X alkylation (X=O, S) of the heterocycles followed by ?X- to ?N-alkyl group migrations in a single step. (Figure presented.).

Manganese-Promoted Regioselective Direct C3-Phosphinoylation of 2-Pyridones

A highly efficient and regioselective manganese-induced radical oxidative direct C?P bond formation between 2-pyridones and secondary phosphine oxides was developed. The C3-selective phosphinoylation was conveniently achieved through a combination of substoichiometric manganese and persulfate oxidant under mild conditions. Various 3-phosphinoylated pyridone products can be obtained in moderate to high yields. Preliminary mechanistic studies suggest that the reaction is likely to involve a radical pathway induced by catalytically active Mn3+ species.

Iron-Catalyzed Reactions of 2-Pyridone Derivatives: 1,6-Addition and Formal Ring Opening/Cross Coupling

In the presence of simple iron salts, 2-pyridone derivatives react with Grignard reagents under mild conditions to give the corresponding 1,6-addition products; if the reaction medium is supplemented with an aprotic dipolar cosolvent after the actual addition step, the intermediates primarily formed succumb to ring opening, giving rise to non-thermodynamic Z,E-configured dienoic acid amide derivatives which are difficult to make otherwise. Control experiments as well as the isolation and crystallographic characterization of a (tricarbonyl)iron pyridone complex suggest that the active iron catalyst generated in situ exhibits high affinity to the polarized diene system embedded into the heterocyclic ring system of the substrates, which likely serves as the actual recognition element.

Iridium-Catalysed C-H Borylation of 2-Pyridones; Bisfunctionalisation of CC4

The high regioselectivity associated with the iridium-catalysed borylation of pyridones has been exploited to provide a very direct and efficient entry to C(10) doubly substituted CC4 variants of cytisine. Two approaches have been evaluated based on (i) C-H activation of cytisine (or an N-substituted derivative) followed by N-alkylation (to enable dimer formation) and (ii) direct C-H activation and borylation of CC4 itself. Both approaches provide access to C(10)-functionalized CC4 derivatives, but direct borylation of CC4 allows for a wider range of functional group interconversions to be tolerated.

Design and Characterization of Novel Covalent Bromodomain and Extra-Terminal Domain (BET) Inhibitors Targeting a Methionine

BET proteins are key epigenetic regulators that regulate transcription through binding to acetylated lysine (AcLys) residues of histones and transcription factors through bromodomains (BDs). The disruption of this interaction with small molecule bromodomain inhibitors is a promising approach to treat various diseases including cancer, autoimmune and cardiovascular diseases. Covalent inhibitors can potentially offer a more durable target inhibition leading to improved in vivo pharmacology. Here we describe the design of covalent inhibitors of BRD4(BD1) that target a methionine in the binding pocket by attaching an epoxide warhead to a suitably oriented noncovalent inhibitor. Using thermal denaturation, MALDI-TOF mass spectrometry, and an X-ray crystal structure, we demonstrate that these inhibitors selectively form a covalent bond with Met149 in BRD4(BD1) but not other bromodomains and provide durable transcriptional and antiproliferative activity in cell based assays. Covalent targeting of methionine offers a novel approach to drug discovery for BET proteins and other targets.

PYRIDONE DERIVATIVES AND THEIR USE AS KINASE INHIBITORS

Disclosed in the present application is a compound of formula (I) as defined herein as well as a pharmaceutical composition comprising said compound. Further disclosed in the present application is the use of such pharmaceutical compositions for treating diseases, namely inter alia for use in the treatment of cancer, metabolic, inflammatory, autoimmune and viral diseases. The compounds disclosed herein are inhibitors of MNK1 and/or MNK2 kinases.

Mild and Regioselective N-Alkylation of 2-Pyridones in Water

A mild and regioselective N-alkylation reaction of 2-pyridones in water has been developed. Tween 20 (2% w/w) was added to create a micellar system for improved solubility of starting materials, which leads to enhanced reaction rates. The protocol demonstrated a wide substrate scope with good isolated yields (40-94%) for all of the 24 examples evaluated. High regioselectivity favoring N-alkylation over O-alkylation was observed for benzyl halides (>5:1), primary alkyl halides (>6:1), and bulky and less reactive secondary alkyl halides (>2.4:1).

INHIBITORS OF VIRAL REPLICATION, THEIR PROCESS OF PREPARATION AND THEIR THERAPEUTICAL USES

Inhibitors of viral replication of formula (I), their process of preparation and their therapeutical uses. The present invention relates to compounds, their use in the treatment or the prevention of viral disorders, including HIV.

Novel Heterocyclic Compounds as Bromodomain Inhibitors

The present disclosure relates to compounds, which are useful for inhibition of BET protein function by binding to bromodomains, and their use in therapy.

Synthesis and evaluation of pyridone-phenoxypropyl-R-2-methylpyrrolidine analogues as histamine H3 receptor antagonists

6-{4-[3-(R)-2-Methylpyrrolidin-1-yl)propoxy]-phenyl}-2H-pyridazin-3-one 6 (Irdabisant; CEP-26401) was recently reported as a potent H3R antagonist with excellent drug-like properties and in vivo activity that advanced into clinical evaluation. A series of pyridone analogs of 6 was synthesized and evaluated as H3R antagonists. Structure-activity relationships revealed that the 5-pyridone regiomer was optimal for H 3R affinity. N-Methyl 9b showed excellent H3R affinity, acceptable pharmacokinetics and pharmaceutical properties. In vivo evaluation of 9b showed potent activity in the rat dipsogenia model and robust wake-promoting activity in the rat EEG model.