874902-19-9

Basic information

• Product Name: 5-[[(1,1'-BIPHENYL)-4-YL]METHYL]-N,N-DIMETHYL-1H-TETRAZOLE-1-CARBOXAMIDE
• Synonyms: LY 2183240;5-[[(1,1'-BIPHENYL)-4-YL]METHYL]-N,N-DIMETHYL-1H-TETRAZOLE-1-CARBOXAMIDE;5-(biphenyl-4-ylMethyl)-N,N-diMethyl-1H-tetrazole-1-carboxaMide;LY-2183240 MN-25;1H-Tetrazole-1-carboxamide, 5-([1,1′-biphenyl]-4-ylmethyl)-N,N-dimethyl-;5-Biphenyl-4-ylmethyl-tetrazole-1-carboxylic acid dimethylamide;N,N-dimethyl-5-[(4-phenylphenyl)methyl]tetrazole-1-carboxamide;LY2183240/LY-2183240
• CAS NO: 874902-19-9
• Molecular Formula: C17H17N5O
• Molecular Weight: 307.34978
• Mol File: 874902-19-9.mol

Chemical Properties

• Melting Point: 87-88℃
• Boiling Point: 506.103 °C at 760 mmHg
• Flash Point: 259.882 °C
• Appearance: /
• Density: 1.21
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.64
• Storage Temp.: Store at +4°C
• Solubility: Soluble in DMSO (greater than 25 mg/ml) or in Ethanol (up to 15 mg/ml).
• PKA: 0.01±0.10(Predicted)
• Stability: Stable for 1 year as supplied. Solutions in DMSO of ethanol may be stored at -20°C for up to 1 month
• CAS DataBase Reference: 5-[[(1,1'-BIPHENYL)-4-YL]METHYL]-N,N-DIMETHYL-1H-TETRAZOLE-1-CARBOXAMIDE(CAS DataBase Reference)
• NIST Chemistry Reference: 5-[[(1,1'-BIPHENYL)-4-YL]METHYL]-N,N-DIMETHYL-1H-TETRAZOLE-1-CARBOXAMIDE(874902-19-9)
• EPA Substance Registry System: 5-[[(1,1'-BIPHENYL)-4-YL]METHYL]-N,N-DIMETHYL-1H-TETRAZOLE-1-CARBOXAMIDE(874902-19-9)

Safety Data

• Hazard Codes: Xn
• Statements: 22
• Hazardous Substances Data: 874902-19-9(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
5-[[(1,1'-BIPHENYL)-4-YL]METHYL]-N,N-DIMETHYL-1H-TETRAZOLE-1-CARBOXAMIDE is used as a research chemical for the development of new drugs targeting the endocannabinoid system. Its ability to inhibit FAAH activity and anandamide uptake makes it a potential candidate for the treatment of various disorders related to the endocannabinoid system, such as pain, inflammation, and neurodegenerative diseases.
Used in Neuroscience Research:
5-[[(1,1'-BIPHENYL)-4-YL]METHYL]-N,N-DIMETHYL-1H-TETRAZOLE-1-CARBOXAMIDE is used as a research tool in neuroscience to study the role of the endocannabinoid system in various physiological and pathological processes. Its potent inhibitory effects on FAAH and anandamide uptake allow researchers to investigate the mechanisms underlying the endocannabinoid system's involvement in cognitive function, mood regulation, and other neurological conditions.
Used in Drug Development:
5-[[(1,1'-BIPHENYL)-4-YL]METHYL]-N,N-DIMETHYL-1H-TETRAZOLE-1-CARBOXAMIDE is used as a lead compound in the development of new synthetic cannabinoids with potential therapeutic applications. Its unique chemical structure and pharmacological properties make it a valuable starting point for the design and synthesis of novel compounds with improved efficacy, selectivity, and safety profiles.
Used in Drug Screening and Assay Development:
5-[[(1,1'-BIPHENYL)-4-YL]METHYL]-N,N-DIMETHYL-1H-TETRAZOLE-1-CARBOXAMIDE is used as a reference compound in drug screening and assay development for the identification and evaluation of new FAAH inhibitors and other modulators of the endocannabinoid system. Its well-defined pharmacological profile and potency enable researchers to develop reliable and sensitive assays for the discovery of new therapeutic agents targeting the endocannabinoid system.

Biological Activity

Novel and highly potent blocker of anandamide uptake (IC 50 = 270 pM). Inhibits fatty acid amide hydrolase (FAAH) activity (IC 50 = 12.4 nM). Following i.p. administration in rats, increases brain anandamide concentration and exerts antinociceptive effects in formalin model of pain.

References

1) Moore et al., (2005), Identification of a high-affinity binding site involved in the transport of endocannabinoids; Proc. Natl. Acad. Sci. USA, 102 17852 2) Ortar et al. (2008), Carbamoyl tetrazoles as inhibitors of endocannabinoid inactivation: A critical revision; Eur. .J. Med. Chem., 43 62 3) Alexander and Cravatt (2006), The putative endocannabinoid transport blocker LY2183240 is a potent inhibitor of FAAH and several other brain serine hydrolases; J. Am. Chem. Soc., 128 9699 4) Dickason-Chesterfield et al. (2006), Pharmacological Characterization of Endocannabinoid Transport and Fatty Acid Amide Hydrolase Inhibitors; Cell. Mol. Neurobiol., 26 405

InChI:InChI=1/C17H17N5O/c1-21(2)17(23)22-16(18-19-20-22)12-13-8-10-15(11-9-13)14-6-4-3-5-7-14/h3-11H,12H2,1-2H3

Upstream product

• 79-44-7 N,N-Dimethylcarbamoyl chloride 
• 31603-77-7 4-biphenylacetonitrile 

Relevant articles and documents

The putative endocannabinoid transport blocker LY2183240 is a potent inhibitor of FAAH and several other brain serine hydrolases

How lipid transmitters move within and between cells to communicate signals remains an important and largely unanswered question. Integral membrane transporters, soluble lipid-binding proteins, and metabolic enzymes have all been proposed to collaborative

(4-Phenoxyphenyl)tetrazolecarboxamides and related compounds as dual inhibitors of fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL)

Inhibitors of the enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), the principle enzymes involved in the degradation of endogenous cannabinoids like anandamide and 2- arachidonoylglycerol, have potential utility in the treatment of several disorders including pain, inflammation and anxiety. In the present study, the effectivity and selectivity of eight known FAAH and MAGL inhibitors for inhibition of the appropriate enzyme were measured applying in vitro assays, which work under comparable conditions. Because many of the known FAAH and MAGL inhibitors simply consist of a lipophilic scaffold to which a heterocyclic system is bound, furthermore, different heterocyclic structures were evaluated for their contribution to enzyme inhibition by attaching them to the same lipophilic backbone, namely 4-phenoxybenzene. One of the most active compound synthesized during this investigation was N,N-dimethyl-5-(4-phenoxyphenyl)-2H- tetrazole-2-carboxamide (16) (IC50 FAAH: 0.012 μM; IC50 MAGL: 0.028 μM). This inhibitor was systematically modified in the lipophilic 4-phenoxyphenyl region. Structure-activity relationship studies revealed that the inhibitory potency against FAAH and MAGL, respectively, could still be increased by replacement of the phenoxy residue of 16 by 3-chlorophenoxy (45) or pyrrol-1-yl groups (49). Finally, the tetrazolecarboxamide 16 and some related compounds were tested for metabolic stability with rat liver S9 fractions showing that these kind of FAAH/MAGL inhibitors are readily inactivated by cleavage of the bond between the tetrazole ring and its carboxamide substituent.

INHIBITORS OF FATTY ACID AMIDE HYDROLASE AND MONOACYLGLYCEROL LIPASE FOR MODULATION OF CANNABINOID RECEPTORS

Disclosed are compounds and compositions that inhibit the action of fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MGL), methods of inhibiting FAAH and MGL, methods of modulating cannabinoid receptors, and methods of treating various disorders related to modulation of cannabinoid receptors.

Carbamoyl tetrazoles as inhibitors of endocannabinoid inactivation: A critical revisitation

We have synthesized a series of 18 1,5- and 2,5-disubstituted carbamoyl tetrazoles, including LY2183240 (1) and LY2318912 (7), two compounds previously described as potent inhibitors of the cellular uptake of the endocannabinoid anandamide, and their regioisomers 2 and 8. We confirm that compound 1 is a potent inhibitor of both the cellular uptake and, like the other new compounds synthesized here, the enzymatic hydrolysis of anandamide. With the exception of 9, 12, 15, and the 2,5-regioisomer of LY2183240 2, the other compounds were all found to be weakly active or inactive on anandamide uptake. Several compounds also inhibited the enzymatic hydrolysis of the other main endocannabinoid, 2-arachidonoylglycerol, as well as its enzymatic release from sn-1-oleoyl-2-arachidonoyl-glycerol, at submicromolar concentrations. Four of the novel compounds, i.e. 3, 4, 17, and 18, inhibited anandamide hydrolysis potently (IC50 = 2.1-5.4 nM) and selectively over all the other targets tested (IC50 ≥ 10 μM), thus representing new potentially useful tools for the inhibition of fatty acid amide hydrolase.