169955-74-2

Upstream product

• 98-98-6 2-Picolinic acid 
• 459-57-4 4-fluorobenzaldehyde 
• 460-00-4 1-Bromo-4-fluorobenzene 
• 1121-60-4 pyridine-2-carbaldehyde 
• 352-13-6 4-flourophenylmagnesium bromide 
• 457-61-4 2-(4-fluorobenzyl)pyridine 
• 109-04-6 2-bromo-pyridine 
• 67-68-5 dimethyl sulfoxide 
• 100-70-9 2-Cyanopyridine 

Downstream Products

• 1613186-48-3 2-[(4-fluorophenyl)(hydrazono)methyl]pyridine 
• 1613186-53-0 3-(4-fluorophenyl)-[1,2,3]triazolo[1,5-a]pyridine 
• 427-42-9 (4-fluorophenyl)(phenyl)(pyridin-2-yl)methanol 
• 1443984-93-7 2-((4-fluorophenyl)(phenyl)methyl)pyridine 
• 457-61-4 2-(4-fluorobenzyl)pyridine 

Relevant academic research and scientific papers

Green synthesis method of polyaryl substituted methanol

The invention relates to a green synthesis method of polyaryl substituted methanol, in particular to a method for efficiently synthesizing polyaryl substituted methanol in a polar aprotic solvent under the condition of an oxidizing agent by taking polyaryl substituted methane as a raw material and alkali as an additive. The method provided by the invention is green and environment-friendly, avoids using expensive metal catalysts, and has the advantages of low cost, few reaction steps, short time, high yield and the like.

Targeting the aryl hydrocarbon receptor with a novel set of triarylmethanes

The aryl hydrocarbon receptor (AhR) is a chemical sensor upregulating the transcription of responsive genes associated with endocrine homeostasis, oxidative balance and diverse metabolic, immunological and inflammatory processes, which have raised the pharmacological interest on its modulation. Herein, a novel set of 32 unsymmetrical triarylmethane (TAM) class of structures has been synthesized, characterized and their AhR transcriptional activity evaluated using a cell-based assay. Eight of the assayed TAM compounds (14, 15, 18, 19, 21, 22, 25, 28) exhibited AhR agonism but none of them showed antagonist effects. TAMs bearing benzotrifluoride, naphthol or heteroaromatic (indole, quinoline or thiophene) rings seem to be prone to AhR activation unlike phenyl substituted or benzotriazole derivatives. A molecular docking analysis with the AhR ligand binding domain (LBD) showed similarities in the binding mode and in the interactions of the most potent TAM identified 4-(pyridin-2-yl (thiophen-2-yl)methyl)phenol (22) compared to the endogenous AhR agonist 5,11-dihydroindolo[3,2-b]carbazole-12-carbaldehyde (FICZ). Finally, in silico predictions of physicochemical and biopharmaceutical properties for the most potent agonistic compounds were performed and these exhibited acceptable druglikeness and good ADME profiles. To our knowledge, this is the first study assessing the AhR modulatory effects of unsymmetrical TAM class of compounds.

Transition-Metal Free Chemoselective Hydroxylation and Hydroxylation-Deuteration of Heterobenzylic Methylenes

We developed an approach for direct selective hydroxylation of heterobenzylic methylenes to secondary alcohols avoiding overoxidation to ketones by using a KOBu-t/DMSO/air system. Most reactions could reach completion in several minutes to give hydroxylated products in 41-76% yields. Using DMSO-d6, this protocol resulted in difunctionalization of heterobenzylic methylenes to afford α-deuterated secondary alcohols (>93% incorporation). By employing this method, active pharmaceutical ingredients carbinoxamine and doxylamine were synthesized in two steps in moderate yields.

NAPHTHYRIDINONE COMPOUNDS USEFUL AS T CELL ACTIVATORS

Disclosed are compounds of Formula (I): or a salt thereof, wherein: R1, R2, R3, and R4 are defined herein. Also disclosed are methods of using such compounds to inhibit the activity of one or both of diacylglycerol kinase alpha (DGK α) and diacylglycerol kinase zeta (DGKζ ), and pharmaceutical compositions comprising such compounds. These compounds are useful in the treatment of viral infections and proliferative disorders, such as cancer.

Conformational Dynamics-Guided Loop Engineering of an Alcohol Dehydrogenase: Capture, Turnover and Enantioselective Transformation of Difficult-to-Reduce Ketones

Directed evolution of enzymes for the asymmetric reduction of prochiral ketones to produce enantio-pure secondary alcohols is particularly attractive in organic synthesis. Loops located at the active pocket of enzymes often participate in conformational changes required to fine-tune residues for substrate binding and catalysis. It is therefore of great interest to control the substrate specificity and stereochemistry of enzymatic reactions by manipulating the conformational dynamics. Herein, a secondary alcohol dehydrogenase was chosen to enantioselectively catalyze the transformation of difficult-to-reduce bulky ketones, which are not accepted by the wildtype enzyme. Guided by previous work and particularly by structural analysis and molecular dynamics (MD) simulations, two key residues alanine 85 (A85) and isoleucine 86 (I86) situated at the binding pocket were thought to increase the fluctuation of a loop region, thereby yielding a larger volume of the binding pocket to accommodate bulky substrates. Subsequently, site-directed saturation mutagenesis was performed at the two sites. The best mutant, where residue alanine 85 was mutated to glycine and isoleucine 86 to leucine (A85G/I86L), can efficiently reduce bulky ketones to the corresponding pharmaceutically interesting alcohols with high enantioselectivities (～99% ee). Taken together, this study demonstrates that introducing appropriate mutations at key residues can induce a higher flexibility of the active site loop, resulting in the improvement of substrate specificity and enantioselectivity. (Figure presented.).

Ligand-Free Iridium-Catalyzed Dehydrogenative ortho C?H Borylation of Benzyl-2-Pyridines at Room Temperature

A convenient and ligand-free iridium-catalyzed dehydrogenative ortho C?H borylation of benzyl-2-pyridines has been developed. The reaction proceeds smoothly at room temperature using pinacolborane as a borylating reagent in the presence of catalytic amount of [IrOMe(COD)]2. The reaction is compatible with many functional groups, providing a vast array of ortho borylated products in moderate to excellent yields with excellent selectivities. (Figure presented.).

Asymmetric Hydroboration of Heteroaryl Ketones by Aluminum Catalysis

A series of methyl aluminum complexes bearing chiral biphenol-type ligands were found to be highly active catalysts in the asymmetric reduction of heterocyclic ketones (S/C = 100-500, ee up to 99%). The protocol is suitable for a wide range of substrates and has a high tolerance to functional groups. The formed 2-heterocyclic-alcohols are valuable building blocks in drug discovery or can be used as ligands in asymmetric catalysis. Isolation and comprehensive characterization of the reaction intermediates support a catalysis cycle proposed by DFT calculations.

Iridium-Catalyzed Highly Enantioselective Transfer Hydrogenation of Aryl N-Heteroaryl Ketones with N-Oxide as a Removable ortho-Substituent

A highly enantioselective transfer hydrogenation of non-ortho-substituted aryl N-heteroaryl ketones, using readily available chiral diamine-derived iridium complex (S,S)-1f as a catalyst and sodium formate as a hydrogen source in a mixture of H2O/i-PrOH (v/v = 1:1) under ambient conditions, is described. The chiral aryl N-heteroaryl methanols were obtained with up to 98.2% ee by introducing an N-oxide as a removable ortho-substituent. In contrast, no more than 15.1% ee was observed in the absence of an N-oxide moiety. Furthermore, the practical utility of this protocol was also demonstrated by gram-scale asymmetric synthesis of bepotastine besilate in 51% total yield and 99.9% ee.

Nickel-Catalyzed Hydrogenolysis and Conjugate Addition of 2-(Hydroxymethyl)pyridines via Organozinc Intermediates

2-Hydroxymethylpyridines undergo nickel-catalyzed hydrogenolysis upon activation with a chlorophosphate. Reactions employ diethylzinc and are proposed to proceed through secondary benzylzinc reagents. Quenching with deuteromethanol provides straightforward incorporation of a deuterium label in the benzylic position. Intramolecular conjugate additions with α,β-unsaturated esters are also demonstrated and support the intermediacy of a benzylzinc complex.

DOPAMINE D2 RECEPTOR LIGANDS

The present invention relates to novel dopamine D2 receptor ligands. The invention further relates to functionally-biased dopamine D2 receptor ligands and the use of these compounds for treating or preventing central nervous system and systemic disorders associated with dysregulation of dopaminergic activity.