1010096-65-7

Basic information

• Product Name: 2H-Tetrazole-2-carboxaMide, 5-([1,1'-biphenyl]-4-ylMethyl)-N,N-diMethyl-
• Synonyms: 2H-Tetrazole-2-carboxaMide, 5-([1,1'-biphenyl]-4-ylMethyl)-N,N-diMethyl-;LY2183240 2’-isomer;LY2183240 2'-isomer Exclusive;5-([1,1-biphenyl]-4-ylmethyl)-N,N-dimethyl-2H-tetrazole-2-carboxamide
• CAS NO: 1010096-65-7
• Molecular Formula: C₁₇H₁₇N₅O
• Molecular Weight: 307.34978
• Mol File: 1010096-65-7.mol
• Article Data: 3

Chemical Properties

• Boiling Point: 506.103 °C at 760 mmHg
• Flash Point: 259.882 °C
• Appearance: /
• Density: 1.22 g/cm³
• PKA: -1.73±0.12(Predicted)
• CAS DataBase Reference: 2H-Tetrazole-2-carboxaMide, 5-([1,1'-biphenyl]-4-ylMethyl)-N,N-diMethyl-(CAS DataBase Reference)
• NIST Chemistry Reference: 2H-Tetrazole-2-carboxaMide, 5-([1,1'-biphenyl]-4-ylMethyl)-N,N-diMethyl-(1010096-65-7)
• EPA Substance Registry System: 2H-Tetrazole-2-carboxaMide, 5-([1,1'-biphenyl]-4-ylMethyl)-N,N-diMethyl-(1010096-65-7)

Safety Data

• Hazardous Substances Data: 1010096-65-7(Hazardous Substances Data)

Usage

Description

LY2183240 is a potent, competitive small molecule inhibitor of anandamide uptake (IC50 = 270 pM; Ki = 540 pM) and hydrolysis. It has been shown to increase anandamide levels in rat cerebellum (ED50 = 1.37 mg/kg) and displays dose-dependent efficacy (3-30 mg/kg) in several rodent models of persistent pain. LY2183240 2’-isomer is a less potent, 2,5-regioisomer of LY2183240 that inhibits anandamide hydrolysis and uptake with IC50 values of 33 and 998 nM, respectively.

Uses

5-([1,1''-Biphenyl]-4-ylmethyl)-N,N-dimethyl-2H-tetrazole-2-carboxamide is an inhibitor of human monoacylglycerol lipase (hMGL).

Upstream product

• 79-44-7 N,N-Dimethylcarbamoyl chloride 

Relevant articles and documents

(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.

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.