2055172-61-5

Basic information

• Product Name: (S)-(4-([1,1'-biphenyl]-4-yl)-1H-1,2,3-triazol-1-yl)(2-benzylpiperidin-1-yl)methanone
• CAS NO: 2055172-61-5
• Molecular Weight: 422.53
• Mol File: 2055172-61-5.mol

Chemical Properties

• CAS DataBase Reference: (S)-(4-([1,1'-biphenyl]-4-yl)-1H-1,2,3-triazol-1-yl)(2-benzylpiperidin-1-yl)methanone(CAS DataBase Reference)
• NIST Chemistry Reference: (S)-(4-([1,1'-biphenyl]-4-yl)-1H-1,2,3-triazol-1-yl)(2-benzylpiperidin-1-yl)methanone(2055172-61-5)
• EPA Substance Registry System: (S)-(4-([1,1'-biphenyl]-4-yl)-1H-1,2,3-triazol-1-yl)(2-benzylpiperidin-1-yl)methanone(2055172-61-5)

Safety Data

• Hazardous Substances Data: 2055172-61-5(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Development:
(S)-(4-([1,1'-biphenyl]-4-yl)-1H-1,2,3-triazol-1-yl)(2-benzylpiperidin-1-yl)methanone is used as a compound in pharmaceutical development for its potential to be incorporated into new drugs. Its unique molecular structure may allow for the creation of novel therapeutic agents that can target specific biological pathways or receptors.
Used in Medicinal Chemistry Research:
In the field of medicinal chemistry research, (S)-(4-([1,1'-biphenyl]-4-yl)-1H-1,2,3-triazol-1-yl)(2-benzylpiperidin-1-yl)methanone serves as a valuable tool for studying the interactions between biological systems and potential drug candidates. Its complex structure may provide insights into the design and synthesis of new molecules with improved pharmacological properties.
Used in Drug Delivery Systems:
(S)-(4-([1,1'-biphenyl]-4-yl)-1H-1,2,3-triazol-1-yl)(2-benzylpiperidin-1-yl)methanone may also be utilized in the development of drug delivery systems. Its structural features could be exploited to enhance the solubility, stability, or targeted delivery of therapeutic agents, potentially improving their efficacy and reducing side effects.
Used in Chemical Synthesis:
As a complex molecule with multiple functional groups, (S)-(4-([1,1'-biphenyl]-4-yl)-1H-1,2,3-triazol-1-yl)(2-benzylpiperidin-1-yl)methanone could be employed in chemical synthesis processes. It may serve as a building block or intermediate for the creation of more complex molecules with specific applications in various industries, including pharmaceuticals, materials science, and agrochemicals.

Upstream product

• 756462-76-7 (R)-1-benzyl-prop-2-enylamine 
• 244092-76-0 (R)-N-(tert-butoxycarbonyl)-3-amino-4-phenyl-1-butene 
• 77119-85-8 N-(tert-butoxycarbonyl)-D-phenylalaninal 
• 115186-33-9 (R)-tert-butyl (1-(methoxy(methyl)amino)-1-oxo-3-phenylpropan-2-yl)carbamate 
• 18942-49-9 Boc-D-Phe-OH 
• 32315-10-9 bis(trichloromethyl) carbonate 
• 35222-81-2 4-([1,1′-biphenyl]-4-yl)-1H-1,2,3-triazole 
• 99112-94-4 (2S)-2-benzylpiperidine 
• 29079-00-3 4-ethynyl-1,1'-biphenyl 
• 126410-30-8 (S)-1-phenylbut-3-en-2-amine 
• 103127-52-2 ((S)-1-benzylallyl)carbamic acid tert-butyl ester 
• 72155-45-4 Boc-L-phenylalaninal 
• 87694-53-9 Boc-Phe-OH N,O-dimethyl hydroxamate 
• 13734-34-4 N-tert-butoxycarbonyl-L-phenylalanine 

Relevant articles and documents

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.

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.

Development and optimization of piperidyl-1,2,3-triazole ureas as selective chemical probes of endocannabinoid biosynthesis

We have previously shown that 1,2,3-triazole ureas (1,2,3-TUs) act as versatile class of irreversible serine hydrolase inhibitors that can be tuned to create selective probes for diverse members of this large enzyme class, including diacylglycerol lipase-β (DAGLβ), a principal biosynthetic enzyme for the endocannabinoid 2-arachidonoylglycerol (2-AG). Here, we provide a detailed account of the discovery, synthesis, and structure-activity relationship (SAR) of (2-substituted)-piperidyl-1,2,3-TUs that selectively inactivate DAGLβ in living systems. Key to success was the use of activity-based protein profiling (ABPP) with broad-spectrum and tailored activity-based probes to guide our medicinal chemistry efforts. We also describe an expanded repertoire of DAGL-tailored activity-based probes that includes biotinylated and alkyne agents for enzyme enrichment coupled with mass spectrometry-based proteomics and assessment of proteome-wide selectivity. Our findings highlight the broad utility of 1,2,3-TUs for serine hydrolase inhibitor development and their application to create selective probes of endocannabinoid biosynthetic pathways.

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.