98061-20-2

Upstream product

• 5029-67-4 2-iodopyridine 
• 93-58-3 benzoic acid methyl ester 
• 618-91-7 methyl 3-iodo-benzoate 
• 17997-47-6 2-tri-n-butylstannylpyridine 
• 618-89-3 methyl 3-bromobenzoate 
• 109-04-6 2-bromo-pyridine 
• 2905-65-9 methyl 3-chlorobenzoate 
• 1008-89-5 2-phenylpyridine 
• 85553-53-3 3-(2-pyridinyl)benzaldehyde 
• 74-88-4 methyl iodide 
• 98-98-6 2-Picolinic acid 
• 67-56-1 methanol 
• 558-13-4 carbon tetrabromide 
• 109-09-1 2-chloropyridine 

Downstream Products

• 1264661-23-5 methyl 4-(benzoxazol-2-yl)-3-(pyridin-2-yl)benzoate 
• 1616246-07-1 (S)-N-(3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl)-3-(pyridin-2-yl)benzamide 
• 1616246-06-0 (R)-N-(3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl)-3-(pyridin-2-yl)benzamide 

Relevant academic research and scientific papers

Porous phosphorescent coordination polymers for oxygen sensing

(Graph Presented) Phosphorescent cyclometalated iridium tris(2-phenylpyridine) derivatives were designed and incorporated into coordination polymers as tricarboxylate bridging ligands. Three different crystalline coordination polymers were synthesized using a solvothermal technique and were characterized using a variety of methods, including single-crystal X-ray diffraction, PXRD, TGA, IR spectroscopy, gas adsorption measurements, and luminescence measurements. The coordination polymer built from Ir[3-(2-pyridyl)benzoate]3, 1, was found to be highly porous with a nitrogen BET surface area of 764 m2/g, whereas the coordination polymers built from Ir[4-(2-pyridyl)benzoate]3, 2 and 3, were nonporous. The 3MLCT phosphorescence of each of the three coordination polymers was quenched in the presence of O2. However, only 1 showed quick and reversible luminescence quenching by oxygen, whereas 2 and 3 exhibited gradual and irreversible luminescence quenching by oxygen. The high permanent porosity of 1 allows for rapid diffusion of oxygen through the open channels, leading to efficient and reversible quenching of the 3MLCT phosphorescence. This work highlights the opportunity of designing highly porous and luminescent coordination polymers for sensing other important analytes. Copyright

Cp*Rh(iii)/boron hybrid catalysis for directed C-H addition to β-substituted α,β-unsaturated carboxylic acids

The C-H bond addition reaction of 2-phenylpyridine derivatives with α,β-unsaturated carboxylic acids catalyzed by Cp*Rh(iii)/BH3·SMe2is reported. Activation of C-H bonds with the rhodium catalyst and activation of α,β-unsaturated carboxylic acids with the boron catalyst cooperatively work, and a BINOL-urea hybrid ligand significantly improved the reactivity. With the optimized hybrid catalytic system, various β-disubstituted carboxylic acids were obtained under mild reaction conditions.

Three-Component Couplings among Heteroarenes, Difluorocyclopropenes, and Water via C-H Activation

Three-component couplings have been realized for efficiently constructing various nitrogen-containing skeletons via C-H activation, where difluorocyclopropenes have been first identified as coupling partners. Many substrates including sp2 and sp3 C-H substrates were well tolerated, furnishing the corresponding products in good yields. Furthermore, a catalyst-dependent reaction was also developed, enabling divergent construction of two different frameworks. The application value of these reactions was demonstrated in gram-scale experiments with as little as 1 mol % catalyst.

Ruthenium-Catalyzed meta-Selective CAr-H Bond Formylation of Arenes

The meta-CAr-H bond formylation of arenes has been achieved using CHBr3 as a formyl source in the presence of [Ru(p-cym)(OAc)2] as a catalyst. This method provides efficient access to the preparation of various meta-substituted aromatic compounds, such as alcohols, ethers, amines, nitriles, alkenes, halogens, carboxylic acids, and their derivatives, through transformation of the versatile formyl group. Furthermore, mechanistic studies show that the key active species is a pentagonal ruthenacycle complex.

N-heterocyclic carbene enabled rhodium-catalyzed ortho C(sp2)-H borylation at room temperature

We report a rhodium-catalyzed ortho C(sp2)-H borylation of 2-phenylpyridines using commercially available N-heterocyclic carbenes (NHCs) as ligand and pinacolatodiboron (B2pin2) as borylating reagent. The reaction could take place at room temperature, tolerating a wide range of functionalities and affording ortho borylated products in moderate to excellent yields. The current method is also applicable to gram-scale reaction with reduced catalyst loading.

Enabling Catalytic Arene C-H Amidomethylation via Bis(tosylamido)methane as a Sustainable Formaldimine Releaser

Addition of catalytic arene C-H to formaldimines has been enabled by Ru(II)-catalyzed amidomethylation with bis(tosylamido)methane as a catalytic formaldimine releaser. The new process provides an atom-efficient and sustainable solution to address the challenges of formaldimines in this type of transformation. Furthermore, new synthetic routes based on this catalytic system have been developed for step-efficient access to N-heterotricyclic core structures that are pharmaceutically relevant.

Sterol 14α-Demethylase Structure-Based Design of VNI ((R)- N-(1-(2,4-Dichlorophenyl)-2-(1 H-imidazol-1-yl)ethyl)-4-(5-phenyl-1,3,4-oxadiazol-2-yl)benzamide)) Derivatives to Target Fungal Infections: Synthesis, Biological Evaluation, and Crystallographic Analysis

Because of the increase in the number of immunocompromised patients, the incidence of invasive fungal infections is growing, but the treatment efficiency remains unacceptably low. The most potent clinical systemic antifungals (azoles) are the derivatives of two scaffolds: ketoconazole and fluconazole. Being the safest antifungal drugs, they still have shortcomings, mainly because of pharmacokinetics and resistance. Here, we report the successful use of the target fungal enzyme, sterol 14α-demethylase (CYP51), for structure-based design of novel antifungal drug candidates by minor modifications of VNI [(R)-N-(1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethyl)-4-(5-phenyl-1,3,4-oxadiazol-2-yl)benzamide)], an inhibitor of protozoan CYP51 that cures Chagas disease. The synthesis of fungi-oriented VNI derivatives, analysis of their potencies to inhibit CYP51s from two major fungal pathogens (Aspergillus fumigatus and Candida albicans), microsomal stability, effects in fungal cells, and structural characterization of A. fumigatus CYP51 in complexes with the most potent compound are described, offering a new antifungal drug scaffold and outlining directions for its further optimization.

Transition-Metal-Free Decarboxylative Arylation of 2-Picolinic Acids with Arenes under Air Conditions

A facile, transition-metal-free, and direct decarboxylative arylation of 2-picolinic acids with simple arenes is described. The oxidative decarboxylative arylation of 2-picolinic acids with arenes proceeds readily via N-chloro carbene intermediates to afford 2-arylpyridines in satisfactory to good yields under transition-metal-free conditions. This new type of decarboxylative arylation is operationally simple and scalable and exhibits high functional-group tolerance. Various synthetically useful functional groups, such as halogen atoms, methoxycarbonyl, and nitro, remain intact during the decarboxylative arylation of 2-picolinic acids.

Structure and Property Guided Design in the Identification of PRMT5 Tool Compound EPZ015666

The recent publication of a potent and selective inhibitor of protein methyltransferase 5 (PRMT5) provides the scientific community with in vivo-active tool compound EPZ015666 (GSK3235025) to probe the underlying pharmacology of this key enzyme. Herein, we report the design and optimization strategies employed on an initial hit compound with poor in vitro clearance to yield in vivo tool compound EPZ015666 and an additional potent in vitro tool molecule EPZ015866 (GSK3203591).

PRMT5 INHIBITORS AND USES THEREOF

Described herein are compounds of formula (A), pharmaceutically acceptable salts thereof, and pharmaceutical com-positions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity. Methods of using the compounds for treating PRMT5-mediated disorders are also described.