35222-81-2

Upstream product

• 4648-54-8 trimethylsilylazide 
• 29079-00-3 4-ethynyl-1,1'-biphenyl 
• 71559-15-4 2-azido-1-<(1,1'-biphenyl)-4-yl>ethanone 
• 1576-35-8 toluene-4-sulfonic acid hydrazide 
• 92-91-1 biphenyl-4-acetaldehyde 
• 128256-32-6 C₂₀H₁₇BrN₂O₂S 
• 135-73-9 2-Bromo-4'-phenylacetophenone 

Downstream Products

• 1402612-65-0 (4-([1,1'-biphenyl]-4-yl)-1H-1,2,3-triazol-1-yl)(2-phenylpiperidin-1-yl)methanone 
• 1402612-55-8 (4-([1,1′-biphenyl]4-yl)-1H-1,2,3-triazol-1-yl)(2-benzylpiperidin-1-yl)methanone 
• 2055172-61-5 (R)-(4-([1,1'-biphenyl]-4-yl)-1H-1,2,3-triazol-1-yl)(2-benzylpiperidin-1-yl)methanone 
• 2055172-61-5 (S)-(4-([1,1'-biphenyl]-4-yl)-1H-1,2,3-triazol-1-yl)(2-benzylpiperidin-1-yl)methanone 

Relevant academic research and scientific papers

Iodine-Mediated Condensation–Cyclization of α-Azido Ketones with p-Toluenesulfonyl Hydrazide for Synthesis of 4-Aryl-NH-1,2,3-Triazoles

A molecular iodine mediated condensation–cyclization reaction for the synthesis of 4-aryl-NH-1,2,3-triazoles has been developed from readily available α-azido acetophenones and p-toluenesulfonyl hydrazide. This reaction provides a metal-free strategy for the sequential formation of C–N and N–N bonds in mild condition.

Direct Synthesis of 4-Aryl-1,2,3-triazoles via I2-Promoted Cyclization under Metal- And Azide-Free Conditions

We herein report an iodine-mediated formal [2 + 2 + 1] cyclization of methyl ketones, p-toluenesulfonyl hydrazines, and 1-aminopyridinium iodide for preparation of 4-aryl-NH-1,2,3-triazoles under metal- and azide-free conditions. Notably, this is achieved

Structure Kinetics Relationships and Molecular Dynamics Show Crucial Role for Heterocycle Leaving Group in Irreversible Diacylglycerol Lipase Inhibitors

Drug discovery programs of covalent irreversible, mechanism-based enzyme inhibitors often focus on optimization of potency as determined by IC50-values in biochemical assays. These assays do not allow the characterization of the binding activity (Ki) and reactivity (kinact) as individual kinetic parameters of the covalent inhibitors. Here, we report the development of a kinetic substrate assay to study the influence of the acidity (pKa) of heterocyclic leaving group of triazole urea derivatives as diacylglycerol lipase (DAGL)-α inhibitors. Surprisingly, we found that the reactivity of the inhibitors did not correlate with the pKa of the leaving group, whereas the position of the nitrogen atoms in the heterocyclic core determined to a large extent the binding activity of the inhibitor. This finding was confirmed and clarified by molecular dynamics simulations on the covalently bound Michaelis-Menten complex. A deeper understanding of the binding properties of covalent serine hydrolase inhibitors is expected to aid in the discovery and development of more selective covalent inhibitors.

On Water Cu@g-C3N4 Catalyzed Synthesis of NH-1,2,3-Triazoles via [2+3] Cycloadditions of Nitroolefins/Alkynes and Sodium Azide

Here, we have reported fabrication of graphitic polymeric C3N4 supported CuCl2 (Cu@g-C3N4) and characterized by powder X-ray diffraction, field emission scanning electron microscopy, high resolution transmission electron microscopy, X-ray photoelectron spectroscopy studies. An efficient and regioselective protocol for the on water synthesis of 4-aryl-NH-1,2,3-triazole derivatives via 1,3-diipolar cycloaddition reactions of nitroolefins/phenylacetylenes to sodium azide were demonstrated by using Cu@g-C3N4 as robust and reusable catalyst.

Triazole Ureas Act as Diacylglycerol Lipase Inhibitors and Prevent Fasting-Induced Refeeding

Triazole ureas constitute a versatile class of irreversible inhibitors that target serine hydrolases in both cells and animal models. We have previously reported that triazole ureas can act as selective and CNS-active inhibitors for diacylglycerol lipases (DAGLs), enzymes responsible for the biosynthesis of 2-arachidonoylglycerol (2-AG) that activates cannabinoid CB1 receptor. Here, we report the enantio- and diastereoselective synthesis and structure-activity relationship studies. We found that 2,4-substituted triazole ureas with a biphenylmethanol group provided the most optimal scaffold. Introduction of a chiral ether substituent on the 5-position of the piperidine ring provided ultrapotent inhibitor 38 (DH376) with picomolar activity. Compound 38 temporarily reduces fasting-induced refeeding of mice, thereby emulating the effect of cannabinoid CB1-receptor inverse agonists. This was mirrored by 39 (DO34) but also by the negative control compound 40 (DO53) (which does not inhibit DAGL), which indicates the triazole ureas may affect the energy balance in mice through multiple molecular targets.

Synthesis of N-unsubstituted 1,2,3-triazoles via aerobic oxidative N-dealkylation using copper(II) acetate

A copper-catalyzed aerobic oxidative C[sbnd]N bond cleavage reaction was developed for the synthesis of 4-substituted-NH-1,2,3-triazoles. Diverse β-ketotriazoles derivatives, which are the starting materials for the aerobic oxidative C[sbnd]N bond cleavage reaction, were prepared from nine aryl and seven alkyl alkynes and α-azidoacetophenone by a copper(I)-catalyzed [3?+?2]cycloaddition reaction. The aerobic oxidation of α-(1,2,3-triazol-1-yl)acetophenones using a catalytic amount of copper(II) acetate in the presence oxygen under neutral conditions gave the title compounds in high yield.

N1- AND N2-CARBAMOYL-1,2,3-TRIAZOLE SERINE HYDROLASE INHIBITORS AND METHODS

The present invention provides inhibitors of a wide variety of serine hydrolase enzymes. The inhibitors of the present invention are N1- and N2-carbamoyl-1,2,3-triazole compounds such as those of Formula (I): (Formula (I)) in which N1, N2 and N3 are the nitrogen atoms at positions 1, 2, and 3, respectively, of the triazole ring, and R4, R5, R6, and R7 in Formula (I) are as described herein. Methods of inhibiting serine hydrolase enzymes and methods of preparing carbamoyl-1,2,3-triazole compounds also are described.

Synthesis of 1,2,3-triazoles

4-Phenyl-1-(p-toluenesulfonamido)-1,2,3-triazole (1) is obtained when phenacyl halides react with tosyl hydrazide in one-pot process.

Thermolysis of α-Azidoacetophenone Phenylsulfonylhydrazones. A New Preparative Route to 4-Aryl-1H-1,2,3-triazoles

Thermolysis of α-azidoacetophenone phenylsulfonylhydrazones gave 4-aryl-1H-1,2,3-triazoles in good yields.The reaction proceeds probably via the elimination of benzenesulfinic acid from 4-aryl-2-phenylsulfonyltriazolines formed intermediately.