Literature summary for 3.5.1.99 extracted from

Terwege, T.; Hanekamp, W.; Garzinsky, D.; Koenig, S.; Koch, O.; Lehr, M.
omega-Imidazolyl- and omega-tetrazolylalkylcarbamates as inhibitors of fatty acid amide hydrolase Biological activity and in vitro metabolic stability (2016), ChemMedChem, 11, 429-443 .

Inhibitors

Inhibitors	Comment	Organism
2-fluorophenyl [6-(5-phenyl-2H-tetrazol-2-yl)hexyl]carbamate	-	Rattus norvegicus
3'-carbamoyl[1,1'-biphenyl]-3-yl cyclohexylcarbamate	-	Rattus norvegicus
4-fluorophenyl [6-(5-phenyl-2H-tetrazol-2-yl)hexyl]carbamate	-	Rattus norvegicus
4-methoxyphenyl [6-(5-phenyl-2H-tetrazol-2-yl)hexyl]carbamate	-	Rattus norvegicus
additional information	structure-activity relationship studies on a series of aryl N-(omega-imidazolyl- and omega-tetrazolylalkyl)carbamate inhibitors are investigated. A pronounced increase in inhibitory potency is observed if a phenyl residue attached to the carbamate oxygen atom is replaced by a pyridin-3-yl moiety. The most active compounds exhibit IC50 values in the low nanomolar range. Investigations on the metabolic properties of these inhibitors are performed. In rat liver homogenate and in porcine plasma, the extent of their degradation is shown to be strongly dependent on the kind of aryl residue bound to the carbamate as well as on the length and type of the alkyl spacer connecting the carbamate group with the heterocyclic system	Rattus norvegicus
phenyl ([4-[(5-phenyl-2H-tetrazol-2-yl)methyl]phenyl]methyl)carbamate	-	Rattus norvegicus
phenyl [2-[2-(5-phenyl-2H-tetrazol-2-yl)ethoxy]ethyl]carbamate	-	Rattus norvegicus
phenyl [5-(2-phenyl-1H-imidazol-1-yl)pentyl]carbamate	-	Rattus norvegicus
phenyl [5-(5-phenyl-2H-tetrazol-2-yl)pentyl]carbamate	-	Rattus norvegicus
phenyl [6-(1H-imidazol-1-yl)hexyl]carbamate	-	Rattus norvegicus
phenyl [6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexyl]carbamate	-	Rattus norvegicus
phenyl [6-(2-phenyl-1H-imidazol-1-yl)hexyl]carbamate	-	Rattus norvegicus
phenyl [6-(4,5-diphenyl-1H-imidazol-1-yl)hexyl]carbamate	-	Rattus norvegicus
phenyl [6-(4-phenyl-1H-imidazol-1-yl)hexyl]carbamate	-	Rattus norvegicus
phenyl [6-(5-benzyl-2H-tetrazol-2-yl)hexyl]carbamate	-	Rattus norvegicus
phenyl [6-(5-phenyl-1H-imidazol-1-yl)hexyl]carbamate	-	Rattus norvegicus
phenyl [6-(5-phenyl-1H-tetrazol-1-yl)hexyl]carbamate	-	Rattus norvegicus
phenyl [6-(5-phenyl-2H-tetrazol-2-yl)hexyl]carbamate	-	Rattus norvegicus
phenyl [6-[2-(3-chlorophenyl)-1H-imidazol-1-yl]hexyl]carbamate	-	Rattus norvegicus
phenyl [6-[2-(3-fluorophenyl)-1H-imidazol-1-yl]hexyl]carbamate	-	Rattus norvegicus
phenyl [6-[2-(3-methoxyphenyl)-1H-imidazol-1-yl]hexyl]carbamate	-	Rattus norvegicus
phenyl [6-[2-(3-methylphenyl)-1H-imidazol-1-yl]hexyl]carbamate	-	Rattus norvegicus
phenyl [6-[2-(4-chlorophenyl)-1H-imidazol-1-yl]hexyl]carbamate	-	Rattus norvegicus
phenyl [6-[5-(2-chlorophenyl)-2H-tetrazol-2-yl]hexyl]carbamate	-	Rattus norvegicus
phenyl [6-[5-(3-chlorophenyl)-2H-tetrazol-2-yl]hexyl]carbamate	-	Rattus norvegicus
phenyl [6-[5-(4-chlorophenyl)-2H-tetrazol-2-yl]hexyl]carbamate	-	Rattus norvegicus
phenyl [6-[5-(pyridin-2-yl)-2H-tetrazol-2-yl]hexyl]carbamate	-	Rattus norvegicus
phenyl [6-[5-(pyridin-3-yl)-2H-tetrazol-2-yl]hexyl]carbamate	-	Rattus norvegicus
phenyl [6-[5-(pyridin-4-yl)-2H-tetrazol-2-yl]hexyl]carbamate	-	Rattus norvegicus
phenyl [7-(2-phenyl-1H-imidazol-1-yl)heptyl]carbamate	-	Rattus norvegicus
phenyl [7-(5-phenyl-2H-tetrazol-2-yl)heptyl]carbamate	-	Rattus norvegicus
phenyl [8-(2-phenyl-1H-imidazol-1-yl)octyl]carbamate	-	Rattus norvegicus
phenyl [8-(5-phenyl-2H-tetrazol-2-yl)octyl]carbamate	-	Rattus norvegicus
pyridin-3-yl [6-(5-phenyl-2H-tetrazol-2-yl)hexyl]carbamate	-	Rattus norvegicus

Organism

Organism	UniProt	Comment	Textmining
Rattus norvegicus	P97612	-	-

Source Tissue

Source Tissue	Comment	Organism	Textmining
brain	-	Rattus norvegicus	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
N-(2-hydroxyethyl)-4-pyren-1-ylbutanamide + H2O	-	Rattus norvegicus	4-(pyren-1-yl)butanamide + ethylene glycol	-	?

Synonyms

Synonyms	Comment	Organism
FAAH	-	Rattus norvegicus

IC50 Value

IC50 Value	IC50 Value Maximum	Comment	Organism	Inhibitor
0.0000053	-	50 mM Tris-HCl, containing 1 mM sodium EDTA, pH 7.4 at 20°C	Rattus norvegicus	4-methoxyphenyl [6-(5-phenyl-2H-tetrazol-2-yl)hexyl]carbamate
0.000011	-	50 mM Tris-HCl, containing 1 mM sodium EDTA, pH 7.4 at 20°C	Rattus norvegicus	pyridin-3-yl [6-(5-phenyl-2H-tetrazol-2-yl)hexyl]carbamate
0.000054	-	50 mM Tris-HCl, containing 1 mM sodium EDTA, pH 7.4 at 20°C	Rattus norvegicus	phenyl [6-[2-(3-chlorophenyl)-1H-imidazol-1-yl]hexyl]carbamate
0.000075	-	50 mM Tris-HCl, containing 1 mM sodium EDTA, pH 7.4 at 20°C	Rattus norvegicus	phenyl [6-[2-(3-methylphenyl)-1H-imidazol-1-yl]hexyl]carbamate
0.000081	-	50 mM Tris-HCl, containing 1 mM sodium EDTA, pH 7.4 at 20°C	Rattus norvegicus	phenyl [7-(5-phenyl-2H-tetrazol-2-yl)heptyl]carbamate
0.000112	-	50 mM Tris-HCl, containing 1 mM sodium EDTA, pH 7.4 at 20°C	Rattus norvegicus	3'-carbamoyl[1,1'-biphenyl]-3-yl cyclohexylcarbamate
0.000112	-	50 mM Tris-HCl, containing 1 mM sodium EDTA, pH 7.4 at 20°C	Rattus norvegicus	phenyl [6-[2-(3-fluorophenyl)-1H-imidazol-1-yl]hexyl]carbamate
0.000112	-	50 mM Tris-HCl, containing 1 mM sodium EDTA, pH 7.4 at 20°C	Rattus norvegicus	phenyl [8-(5-phenyl-2H-tetrazol-2-yl)octyl]carbamate
0.00018	-	50 mM Tris-HCl, containing 1 mM sodium EDTA, pH 7.4 at 20°C	Rattus norvegicus	phenyl [6-[5-(3-chlorophenyl)-2H-tetrazol-2-yl]hexyl]carbamate
0.000209	-	50 mM Tris-HCl, containing 1 mM sodium EDTA, pH 7.4 at 20°C	Rattus norvegicus	phenyl [6-[5-(2-chlorophenyl)-2H-tetrazol-2-yl]hexyl]carbamate
0.00024	-	50 mM Tris-HCl, containing 1 mM sodium EDTA, pH 7.4 at 20°C	Rattus norvegicus	phenyl [7-(2-phenyl-1H-imidazol-1-yl)heptyl]carbamate
0.00025	-	50 mM Tris-HCl, containing 1 mM sodium EDTA, pH 7.4 at 20°C	Rattus norvegicus	phenyl [6-(5-benzyl-2H-tetrazol-2-yl)hexyl]carbamate
0.00026	-	50 mM Tris-HCl, containing 1 mM sodium EDTA, pH 7.4 at 20°C	Rattus norvegicus	phenyl ([4-[(5-phenyl-2H-tetrazol-2-yl)methyl]phenyl]methyl)carbamate
0.00028	-	50 mM Tris-HCl, containing 1 mM sodium EDTA, pH 7.4 at 20°C	Rattus norvegicus	phenyl [6-[5-(pyridin-2-yl)-2H-tetrazol-2-yl]hexyl]carbamate
0.00029	-	50 mM Tris-HCl, containing 1 mM sodium EDTA, pH 7.4 at 20°C	Rattus norvegicus	phenyl [6-(2-phenyl-1H-imidazol-1-yl)hexyl]carbamate
0.00029	-	50 mM Tris-HCl, containing 1 mM sodium EDTA, pH 7.4 at 20°C	Rattus norvegicus	phenyl [6-[2-(3-methoxyphenyl)-1H-imidazol-1-yl]hexyl]carbamate
0.00033	-	50 mM Tris-HCl, containing 1 mM sodium EDTA, pH 7.4 at 20°C	Rattus norvegicus	2-fluorophenyl [6-(5-phenyl-2H-tetrazol-2-yl)hexyl]carbamate
0.0004	-	50 mM Tris-HCl, containing 1 mM sodium EDTA, pH 7.4 at 20°C	Rattus norvegicus	phenyl [8-(2-phenyl-1H-imidazol-1-yl)octyl]carbamate
0.00042	-	50 mM Tris-HCl, containing 1 mM sodium EDTA, pH 7.4 at 20°C	Rattus norvegicus	phenyl [6-[2-(4-chlorophenyl)-1H-imidazol-1-yl]hexyl]carbamate
0.00043	-	50 mM Tris-HCl, containing 1 mM sodium EDTA, pH 7.4 at 20°C	Rattus norvegicus	phenyl [5-(2-phenyl-1H-imidazol-1-yl)pentyl]carbamate
0.00047	-	50 mM Tris-HCl, containing 1 mM sodium EDTA, pH 7.4 at 20°C	Rattus norvegicus	phenyl [6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexyl]carbamate
0.00048	-	50 mM Tris-HCl, containing 1 mM sodium EDTA, pH 7.4 at 20°C	Rattus norvegicus	phenyl [6-(5-phenyl-1H-imidazol-1-yl)hexyl]carbamate
0.00049	-	50 mM Tris-HCl, containing 1 mM sodium EDTA, pH 7.4 at 20°C	Rattus norvegicus	phenyl [5-(5-phenyl-2H-tetrazol-2-yl)pentyl]carbamate
0.00049	-	50 mM Tris-HCl, containing 1 mM sodium EDTA, pH 7.4 at 20°C	Rattus norvegicus	phenyl [6-(4,5-diphenyl-1H-imidazol-1-yl)hexyl]carbamate
0.00057	-	50 mM Tris-HCl, containing 1 mM sodium EDTA, pH 7.4 at 20°C	Rattus norvegicus	phenyl [6-[5-(4-chlorophenyl)-2H-tetrazol-2-yl]hexyl]carbamate
0.00062	-	50 mM Tris-HCl, containing 1 mM sodium EDTA, pH 7.4 at 20°C	Rattus norvegicus	phenyl [6-(5-phenyl-2H-tetrazol-2-yl)hexyl]carbamate
0.00065	-	50 mM Tris-HCl, containing 1 mM sodium EDTA, pH 7.4 at 20°C	Rattus norvegicus	4-methoxyphenyl [6-(5-phenyl-2H-tetrazol-2-yl)hexyl]carbamate
0.00066	-	50 mM Tris-HCl, containing 1 mM sodium EDTA, pH 7.4 at 20°C	Rattus norvegicus	4-fluorophenyl [6-(5-phenyl-2H-tetrazol-2-yl)hexyl]carbamate
0.00074	-	50 mM Tris-HCl, containing 1 mM sodium EDTA, pH 7.4 at 20°C	Rattus norvegicus	phenyl [6-[5-(pyridin-3-yl)-2H-tetrazol-2-yl]hexyl]carbamate
0.00088	-	50 mM Tris-HCl, containing 1 mM sodium EDTA, pH 7.4 at 20°C	Rattus norvegicus	phenyl [6-(4-phenyl-1H-imidazol-1-yl)hexyl]carbamate
0.0012	-	50 mM Tris-HCl, containing 1 mM sodium EDTA, pH 7.4 at 20°C	Rattus norvegicus	phenyl [6-[5-(pyridin-4-yl)-2H-tetrazol-2-yl]hexyl]carbamate
0.0013	-	50 mM Tris-HCl, containing 1 mM sodium EDTA, pH 7.4 at 20°C	Rattus norvegicus	phenyl [6-(5-phenyl-1H-tetrazol-1-yl)hexyl]carbamate
0.0052	-	50 mM Tris-HCl, containing 1 mM sodium EDTA, pH 7.4 at 20°C	Rattus norvegicus	phenyl [2-[2-(5-phenyl-2H-tetrazol-2-yl)ethoxy]ethyl]carbamate
0.006	-	50 mM Tris-HCl, containing 1 mM sodium EDTA, pH 7.4 at 20°C	Rattus norvegicus	phenyl [6-(1H-imidazol-1-yl)hexyl]carbamate

General Information

General Information	Comment	Organism
metabolism	fatty acid amide hydrolase terminates the analgesic and anti-inflammatory effects of endocannabinoids such as anandamide	Rattus norvegicus