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Merck
CN

SML2732

DO34

≥98% (HPLC)

Synonym(s):

(2-Benzyl-4-{[(2-methyl-2-propanyl)oxy]carbonyl}piperazinyl){4-[(4-trifluoromethoxy)phenyl]-1H-1,2,3-triazol-1-yl}methanone, 3-(Phenylmethyl)-4-[[4-[4-(trifluoromethoxy)phenyl]-1H-1,2,3-triazol-1-yl]carbonyl]-1-piperazinecarboxylic acid, 1,1-dimethylethyl ester

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About This Item

Empirical Formula (Hill Notation):
C26H28F3N5O4
CAS Number:
Molecular Weight:
531.53
UNSPSC Code:
12352200
NACRES:
NA.77
MDL number:
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InChI

1S/C26H28F3N5O4/c1-25(2,3)38-24(36)32-13-14-33(20(16-32)15-18-7-5-4-6-8-18)23(35)34-17-22(30-31-34)19-9-11-21(12-10-19)37-26(27,28)29/h4-12,17,20H,13-16H2,1-3H3

InChI key

CQGMWUWJVBKTRM-UHFFFAOYSA-N

SMILES string

O=C(N1CCN(CC1CC2=CC=CC=C2)C(OC(C)(C)C)=O)N3N=NC(C4=CC=C(C=C4)OC(F)(F)F)=C3

assay

≥98% (HPLC)

form

powder

color

white to beige

solubility

DMSO: 2 mg/mL, clear

storage temp.

−20°C

Quality Level

Biochem/physiol Actions

Brain-penetrant, selective and highly potent diacylglycerol lipase (DAGLα/β, DAGLalpha & DAGLbeta) inhibitor in vitro and in vivo.
DO34 is a brain-penetrant, selective and highly potent diacylglycerol lipase inhibitor (recom human DAGLα/β pIC50 = 8.2/8.1 by SAG hydrolysis; mouse brain DAGLα/β pIC50 = 9.1-9.3/8.6 by ABPP ReDiMe) with detectable off-target activity toward only ABHD6 & PLA2G7 among all mouse brain serine hydrolases and little affinity toward cannabinoid receptors CB1/2. DO34 blocks depolarization-induced suppression of excitation (DSE IC50 = 0.18 μM) and inhibition (100% DSI blockage at 1 μM) in mouse cerebellar and hippocampal slices ex vivo, and attenuate LPS-induced neuroinflammatory responses by lowering brain 2-AG & PGE2 level in mice in vivo (50 mg/kg, i.p).

Storage Class

11 - Combustible Solids

wgk

WGK 3

flash_point_f

Not applicable

flash_point_c

Not applicable


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Carol A Gianessi et al.
Addiction biology, 25(3), e12768-e12768 (2019-05-06)
Individuals with alcohol use disorder exhibit compulsive habitual behaviors that are thought to be, in part, a consequence of chronic and persistent use of alcohol. The endocannabinoid system plays a critical role in habit learning and in ethanol self-administration, but
Daisuke Ogasawara et al.
Proceedings of the National Academy of Sciences of the United States of America, 113(1), 26-33 (2015-12-17)
Diacylglycerol lipases (DAGLα and DAGLβ) convert diacylglycerol to the endocannabinoid 2-arachidonoylglycerol. Our understanding of DAGL function has been hindered by a lack of chemical probes that can perturb these enzymes in vivo. Here, we report a set of centrally active
Jenny L Wilkerson et al.
The Journal of pharmacology and experimental therapeutics, 363(3), 394-401 (2017-10-04)
Diacylglycerol lipase (DAGL) α and β, the major biosynthetic enzymes of the endogenous cannabinoid (endocannabinoid) 2-arachidonylglycerol (2-AG), are highly expressed in the nervous system and immune system, respectively. Genetic deletion or pharmacological inhibition of DAGL-β protects against lipopolysaccharide (LPS)-induced inflammatory
Xiaojie Liu et al.
Scientific reports, 6, 35829-35829 (2016-10-25)
The endocannabinoid 2-arachidonoylglycerol (2-AG) mediates retrograde synaptic depression including depolarization-induced suppression of excitation (DSE) and inhibition (DSI). 2-AG is degraded primarily by monoacylglycerol lipase (MAGL), which is expressed in neurons and astrocytes. Using knockout mice in which MAGL is deleted
Hui Deng et al.
Journal of medicinal chemistry, 60(1), 428-440 (2016-12-20)
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

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