33744-17-1

Usage

InChI:InChI=1/C12H8N2/c13-9-10-6-7-14-12(8-10)11-4-2-1-3-5-11/h1-8H

Upstream product

• 91973-38-5 2-phenylisonicotinamide 
• 100-48-1 pyridine-4-carbonitrile 
• 94-36-0 dibenzoyl peroxide 
• 33252-30-1 2-chloro-4-pyridinenitrile 
• 98-80-6 phenylboronic acid 
• 14906-59-3 4-cyanopyridine N-oxide 
• 5123-13-7 5,5-dimethyl-2-phenyl-1,3,2-dioxaborinane 
• 1008-89-5 2-phenylpyridine 
• 7677-24-9 trimethylsilyl cyanide 
• 24388-23-6 2-phenyl-4,4,5,5-tetramethyl-1,3,2-dioxoborole 
• 19158-51-1 P-toluenesulfonyl cyanide 
• 98420-98-5 4-bromo-2-phenyl pyridine 
• 10386-27-3 2-bromoisonicotinonitrile 
• 92290-75-0 2-chloro-6-phenyl-isonicotinic acid ethyl ester 

Downstream Products

• 96982-28-4 2-phenyl-thioisonicotinic acid amide 
• 55240-51-2 2-phenylpyridine-4-carboxylic acid 
• 501375-49-1 2-(2-Phenyl-4-pyridyl)-4H-1,3-benzothiazine-4-one 

Relevant academic research and scientific papers

Discovery of 9,10-dihydrophenanthrene derivatives as SARS-CoV-2 3CLpro inhibitors for treating COVID-19

The epidemic coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has now spread worldwide and efficacious therapeutics are urgently needed. 3-Chymotrypsin-like cysteine protease (3CLpro) is an indispensable protein in viral replication and represents an attractive drug target for fighting COVID-19. Herein, we report the discovery of 9,10-dihydrophenanthrene derivatives as non-peptidomimetic and non-covalent inhibitors of the SARS-CoV-2 3CLpro. The structure-activity relationships of 9,10-dihydrophenanthrenes as SARS-CoV-2 3CLpro inhibitors have carefully been investigated and discussed in this study. Among all tested 9,10-dihydrophenanthrene derivatives, C1 and C2 display the most potent SARS-CoV-2 3CLpro inhibition activity, with IC50 values of 1.55 ± 0.21 μM and 1.81 ± 0.17 μM, respectively. Further enzyme kinetics assays show that these two compounds dose-dependently inhibit SARS-CoV-2 3CLpro via a mixed-inhibition manner. Molecular docking simulations reveal the binding modes of C1 in the dimer interface and substrate-binding pocket of the target. In addition, C1 shows outstanding metabolic stability in the gastrointestinal tract, human plasma, and human liver microsome, suggesting that this agent has the potential to be developed as an orally administrated SARS-CoV-2 3CLpro inhibitor.

Lewis Basic Salt-Promoted Organosilane Coupling Reactions with Aromatic Electrophiles

Lewis basic salts promote benzyltrimethylsilane coupling with (hetero)aryl nitriles, sulfones, and chlorides as a new route to 1,1-diarylalkanes. This method combines the substrate modularity and selectivity characteristic of cross-coupling with the practicality of a base-promoted protocol. In addition, a Lewis base strategy enables a complementary scope to existing methods, employs stable and easily prepared organosilanes, and achieves selective arylation in the presence of acidic functional groups. The utility of this method is demonstrated by the synthesis of pharmaceutical analogues and its use in multicomponent reactions.

Structure-Activity Relationship for the Picolinamide Antibacterials that Selectively Target Clostridioides difficile

Clostridioides difficile is a leading health threat. This pathogen initiates intestinal infections during gut microbiota dysbiosis caused by oral administration of antibiotics. C. difficile is difficult to eradicate due to its ability to form spores, which are not susceptible to antibiotics. To address the urgent need for treating recurrent C. difficile infection, antibiotics that selectively target C. difficile over common gut microbiota are needed. We herein describe the class of picolinamide antibacterials which show potent and selective activity against C. difficile. The structure-activity relationship of 108 analogues of isonicotinamide 4, a compound that is equally active against methicillin-resistant Staphylococcus aureus and C. difficile, was investigated. Introduction of the picolinamide core as exemplified by analogue 87 resulted in exquisite potency and selectivity against C. difficile. The ability of the picolinamide class to selectively target C. difficile and to prevent gut dysbiosis holds promise for the treatment of recurrent C. difficile infection.

Organophotoredox assisted cyanation of bromoarenes: via silyl-radical-mediated bromine abstraction

The insertion of a nitrile (-CN) group into arenes through the direct functionalization of the C(sp2)-Br bond is a challenging reaction. Herein, we report an organophotoredox method for the cyanation of aryl bromides using the organic photoredox catalyst 4CzIPN and tosyl cyanide (TsCN) as the nitrile source. A photogenerated silyl radical, via a single electron transfer (SET) mechanism, was employed to abstract bromine from aryl bromide to provide an aryl radical, which was concomitantly intercepted by TsCN to afford the aromatic nitrile. A range of substrates containing electron-donating and -withdrawing groups was demonstrated to undergo cyanation at room temperature in good yields.

C6-Selective Direct Arylation of 2-Phenylpyridine via an Activated N-methylpyridinium Salt: A Combined Experimental and Theoretical Study

An elegant pre-activation strategy, based on the formation of N-methylpyridinium iodide salts for C6-selective direct arylation of 2-phenylpyridines using Pd/Cu cooperative catalysis, has been developed. By this methodology, a wide range of unsymmetrical 2, 6-diarylpyridines were synthesized with high reactivity and regioselectivity as well as good functional group tolerance. In particular, challenging substrates bearing electron donating groups (EDGs), such as OMe, NMe2, were also successfully employed in this reaction. Deuterium incorporation studies revealed that the C?H bond acidity is improved significantly in N-methylpyridinium salts compared with their N-Oxide and N-iminopyridinium ylide counterparts, thus solving the long-standing problem associated with previous strategies for the synthesis of diaryl pyridines. Finally, the control experiments and DFT calculations supported a Pd-catalyzed and Cu-mediated mechanism in which a carbenoid copper species that is formed in-situ from N-methylpyridinium salts, participates in a Pd-catalyzed arylation followed by an iodide-promoted N-demethylation process. (Figure presented.).

Direct arylation for the synthesis of 2-arylquinolines from N-methoxyquinoline-1-ium tetrafluoroborate salts and arylboronic acids

A rapid and direct arylation reaction of N-methoxyquinoline-1-ium tetrafluoroborate derivatives and arylboronic acids with high regioselectivety at room temperature was discovered. The reaction shows exceptional functional group tolerance and broad substrate scope regarding both the quinoline derivatives and the arylboronic acids.

Silver-Catalyzed Minisci Reactions Using Selectfluor as a Mild Oxidant

A new method for silver-catalyzed Minisci reactions using Selectfluor as a mild oxidant is reported. Heteroarenes and quinones both participate in radical C-H alkylation and arylation from a variety of carboxylic and boronic acid radical precursors. Several oxidatively sensitive and highly reactive radical species are successful, providing structures that are challenging to access by other means.

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.

METHODS FOR EXTERNAL BASE-FREE SUZUKI COUPLINGS

The present disclosure describes a method of coupling a first aromatic compound to a second aromatic compound, the method comprising: (a) preparing a reaction mixture comprising the first aromatic compound, the second aromatic compound, a catalyst and water; the reaction mixture does not contain an external base, the reaction mixture having an initial pH of from 11 to 1; the catalyst having at least one group 10 atom; the first aromatic compound having a halogen, triflate or sulfonate substituent; the second aromatic compound having a boron-containing substituent; wherein, at least one of the first aromatic compound or the second aromatic compound includes one or more heteroatom; and (b) reacting the first aromatic compound and the second aromatic compound in the reaction mixture, the reaction mixture having a final pH following reaction of the first aromatic compound and the second aromatic compound.

MUSCARINIC M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS

The present invention relates to compound of formula (I), or stereoisomers and pharmaceutically acceptable salts as muscarinic M1 receptor positive allosteric modulators. This invention also relates to methods of preparing such compounds and pharmaceutical compositions comprising such compounds. The compounds of this invention are useful in the treatment of various disorders that are related to muscarinic M1 receptor.