Literature summary for 3.1.1.116 extracted from

Deng, H.; Van Der Wel, T.; Van Den Berg, R.; Van Den Nieuwendijk, A.; Janssen, F.; Baggelaar, M.; Overkleeft, H.; Van Der Stelt, M.
Chiral disubstituted piperidinyl ureas a class of dual diacylglycerol lipase-alpha and ABHD6 inhibitors (2017), MedChemComm, 8, 982-988 .

Search for more literature for 3.1.1.116

Application

Application	Comment	Organism
drug development	inhibitors of diacylglycerol lipases and alpha,beta-hydrolase domain containing protein 6 (ABHD6) are potential leads for the development of therapeutic agents for metabolic and neurodegenerative disorders	Mus musculus

Cloned(Commentary)

Cloned (Comment)	Organism
recombinant expression of DAGLalpha in HEK-293T cells	Mus musculus

Inhibitors

Inhibitors	Comment	Organism
((2R,5R)-2-benzyl-5-[(prop-2-yn-1-yl)oxy]piperidin-1-yl)(4-[bis(4-fluorophenyl)(hydroxy)methyl]-2H-1,2,3-triazol-2-yl)methanone	i.e. DH376, a covalent irreversible inhibitor that features a 2-benzylpiperidine moiety which confers selectivity and activity towards DAGLs and ABHD6	Mus musculus
(4-([1,1'-biphenyl]-4-yl)-1H-1,2,3-triazol-1-yl)((2R,3R)-2-((benzyloxy)methyl)-3-hydroxy-3,6-dihydropyridin-1(2H)-yl)methanone	-	Mus musculus
(4-([1,1'-biphenyl]-4-yl)-1H-1,2,3-triazol-1-yl)((2S,3R)-2-((benzyloxy)methyl)-3-hydroxy-3,6-dihydropyridin-1(2H)-yl)methanone	-	Mus musculus
(4-([1,1'-biphenyl]-4-yl)-1H-1,2,3-triazol-1-yl)((3R,6R)-6-((benzyloxy)methyl)-3-hydroxy-3,6-dihydropyridin-1(2H)-yl)methanone	-	Mus musculus
(4-([1,1'-biphenyl]-4-yl)-1H-1,2,3-triazol-1-yl)((3R,6S)-6-((benzyloxy)methyl)-3-hydroxy-3,6-dihydropyridin-1(2H)-yl)methanone	-	Mus musculus
(4-([1,1'-biphenyl]-4-yl)-1H-1,2,3-triazol-1-yl)((3R,6S)-6-benzyl-3-hydroxy-3,6-dihydropyridin-1(2H)-yl)methanone	-	Mus musculus
(4-([1,1'-biphenyl]-4-yl)-1H-1,2,3-triazol-1-yl)((3S,6R)-6-((benzyloxy)methyl)-3-hydroxy-3,6-dihydropyridin-1(2H)-yl)methanone	-	Mus musculus
(R)-(3-([1,1'-biphenyl]-4-yl)-1H-1,2,4-triazol-1-yl)(6-((benzyloxy)methyl)-3,6-dihydropyridin-1(2H)-yl)methanone	-	Mus musculus
(R)-(3-([1,1'-biphenyl]-4-yl)-1H-pyrazol-1-yl)(6-((benzyloxy)methyl)-3,6-dihydropyridin-1(2H)-yl)methanone	-	Mus musculus
(R)-(4-([1,1'-biphenyl]-4-yl)-1H-1,2,3-triazol-1-yl)(2-((benzyloxy)methyl)piperidin-1-yl)methanone	-	Mus musculus
(R)-(4-([1,1'-biphenyl]-4-yl)-1H-1,2,3-triazol-1-yl)(6-((benzyloxy)methyl)-3,6-dihydropyridin-1(2H)-yl)methanone	-	Mus musculus
(R)-(4-([1,1'-biphenyl]-4-yl)-1H-1,2,3-triazol-1-yl)(6-benzyl-3,6-dihydropyridin51(2H)-yl)methanone	-	Mus musculus
(R)-(6-((benzyloxy)methyl)-3,6-dihydropyridin-1(2H)-yl)(3-(4-bromophenyl)-1H-pyrazol-1-yl)methanone	-	Mus musculus
(R)-(6-((benzyloxy)methyl)-3,6-dihydropyridin-1(2H)-yl)(4-(4-bromophenyl)-1H-1,2,3-triazol-1-yl)methanone	-	Mus musculus
(R)-(6-((benzyloxy)methyl)-3,6-dihydropyridin-1(2H)-yl)(4-(4-bromophenyl)-1H-imidazol-1-yl)methanone	-	Mus musculus
(R)-(6-((benzyloxy)methyl)-3,6-dihydropyridin-1(2H)-yl)(4-(4-nitrophenyl)-1H-1,2,3-triazol-1-yl)methanone	-	Mus musculus
(R)-(6-((benzyloxy)methyl)-3,6-dihydropyridin-1(2H)-yl)(4-(4-phenoxyphenyl)-1H-1,2,3-triazol-1-yl)methanone	-	Mus musculus
(R)-(6-((benzyloxy)methyl)-3,6-dihydropyridin-1(2H)-yl)(4-phenyl-1H-1,2,3-triazol-1-yl)methanone	-	Mus musculus
(S)-(4-([1,1'-biphenyl]-4-yl)-1H-1,2,3-triazol-1-yl)(6-((benzyloxy)methyl)-3,6-dihydropyridin-1(2H)-yl)methanone	-	Mus musculus
4-nitrophenyl (R)-6-((benzyloxy)methyl)-3,6-dihydropyridine-1(2H)-carboxylate	-	Mus musculus
additional information	most DAGL inhibitors cross-react with alpha,beta-hydrolase domain containing protein 6 (ABHD6), which has a minor role in the hydrolysis of 2-AG, degrades bis-(monoacylglycero)-phosphate, and acts as a lysophosphatidyl hydrolase. Enantioselective synthesis and structure activity relationships of triazole ureas featuring chiral, hydroxylated 2-benzylpiperidines as dual inhibitors of DAGLalpha and ABHD6. The chirality of the carbon bearing the C2 substituent, as well as the position of the hydroxyl (tolerated at C5, but not at C3) has profound influence on the inhibitory activity of both DAGLalpha and ABHD6, as established using biochemical assays and competitive activity-based protein profiling on mouse brain extracts. pIC50 values. Structure-activity relationship of the covalent irreversible inhibitors, overview	Mus musculus
tert-butyl 3-benzyl-4-[4-[4-(trifluoromethoxy)phenyl]-1H-1,2,3-triazole-1-carbonyl]piperazine-1-carboxylate	-	Mus musculus
tert-butyl 3-benzyl-4-{4-[4-(trifluoromethoxy)phenyl]-1H-1,2,3-triazole-1-carbonyl}piperazine-1-carboxylate	i.e. DO34, a covalent irreversible inhibitor that features a 2-benzylpiperidine moiety which confers selectivity and activity towards DAGLs and ABHD6	Mus musculus
[(2R)-2-benzylpiperidin-1-yl][4-([1,1'-biphenyl]-4-yl)-1H-1,2,3-triazol-1-yl]methanone	-	Mus musculus
[(2S)-2-benzylpiperidin-1-yl][4-([1,1'-biphenyl]-4-yl)-1H-1,2,3-triazol-1-yl]methanone	-	Mus musculus
[(6S)-6-benzyl-3,6-dihydropyridin-1(2H)-yl][4-([1,1'-biphenyl]-4-yl)-1H-1,2,3-triazol-1-yl]methanone	-	Mus musculus
[[(3R,6R)-6-benzyl-1-[4-[bis(4-fluorophenyl)(hydroxy)methyl]-2H-1,2,3-triazole-2-carbonyl]piperidin-3-yl]oxy]acetonitrile	-	Mus musculus

Localization

Localization	Comment	Organism	GeneOntology No.	Textmining
membrane	-	Mus musculus	16020	-

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
1-acyl-2-arachidonoyl-sn-glycerol + H2O	Mus musculus	-	2-arachidonoylglycerol + fatty acid	-	?

Organism

Organism	UniProt	Comment	Textmining
Mus musculus	Q6WQJ1	-	-

Source Tissue

Source Tissue	Comment	Organism	Textmining
brain	-	Mus musculus	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
1-acyl-2-arachidonoyl-sn-glycerol + H2O	-	Mus musculus	2-arachidonoylglycerol + fatty acid	-	?

Synonyms

Synonyms	Comment	Organism
DAGLalpha	-	Mus musculus
diacylglycerol lipase-alpha	-	Mus musculus

IC50 Value

IC50 Value	IC50 Value Maximum	Comment	Organism	Inhibitor	Structure
additional information	-	pIC50 values, overview	Mus musculus	additional information