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Literature summary for 2.1.1.28 extracted from

  • Grunewald, G.L.; Seim, M.R.; Lu, J.; Makboul, M.; Criscione, K.R.
    Application of the Goldilocks effect to the design of potent and selective inhibitors of phenylethanolamine N-methyltransferase: balancing pKa and steric effects in the optimization of 3-methyl-1,2,3,4-tetrahydroisoquinoline inhibitors by beta-fluorinatio (2006), J. Med. Chem., 49, 2939-2952.
    View publication on PubMedView publication on EuropePMC

Application

Application Comment Organism
additional information selective inhibitors of phenylethanolamine N-methyltransferase would be useful pharmacological tools for clearly defining the connection between central epinephrine concentrations and peripheral blood pressure Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
human phenylethynolamine N-methyltransferase with a C-terminal hexahistidine tag is expressed in Escherichia coli Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
3-difluoromethyl-1,2,3,4-tetrahydroisoquinoline
-
Homo sapiens
3-difluoromethyl-7-(ethylaminosulfonyl)-1,2,3,4-tetrahydroisoquinoline
-
Homo sapiens
3-difluoromethyl-7-(N-2,2,2-trifluoroethylaminosulfonyl)-1,2,3,4-tetrahydroisoquinoline
-
Homo sapiens
3-difluoromethyl-7-(N-3-methoxypropylaminosulfonyl)-1,2,3,4-tetrahydroisoquinoline
-
Homo sapiens
3-difluoromethyl-7-(N-4-nitrophenylaminosulfonyl)-1,2,3,4-tetrahydroisoquinoline
-
Homo sapiens
3-difluoromethyl-7-(propylaminosulfonyl)-1,2,3,4-tetrahydroisoquinoline
-
Homo sapiens
3-difluoromethyl-7-bromo-1,2,3,4-tetrahydroisoquinoline
-
Homo sapiens
3-difluoromethyl-7-cyano-1,2,3,4-tetrahydroisoquinoline
-
Homo sapiens
3-difluoromethyl-7-iodo-1,2,3,4-tetrahydroisoquinoline
-
Homo sapiens
3-difluoromethyl-7-methylsulfonyl-1,2,3,4-tetrahydroisoquinoline
-
Homo sapiens
3-difluoromethyl-7-nitro-1,2,3,4-tetrahydroisoquinoline
-
Homo sapiens
3-difluoromethyl-7-trifluoromethyl-1,2,3,4-tetrahydroisoquinoline
-
Homo sapiens
7-(N-4-chlorophenylaminosulfonyl)-3-difluoromethyl-1,2,3,4-tetrahydroisoquinoline
-
Homo sapiens
7-(N-butylaminosulfonyl)-3-difluoromethyl-1,2,3,4-tetrahydroisoquinoline
-
Homo sapiens
7-aminosulfonyl-3-difluoromethyl-1,2,3,4-tetrahydroisoquinoline
-
Homo sapiens
additional information the rank order of phenylethanolamine N-methyltransferase inhibitory potency for the analysed 3,7-disubstituted-1,2,3,4-tetrahydroisoquinoline is CH2F equal to CHF2 decreases to CF3. The 3-difluoromethyl-7-substituted-1,2,3,4-tetrahydroisoquinolines have the proper balance of steric and pKa properties, they are both potent inhibitors of phenylethanolamine N-methyltransferase and highly selective due to low affinity for the alpha2-adrenoceptor. Homo sapiens

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-

Synonyms

Synonyms Comment Organism
PNMT
-
Homo sapiens

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
0.000067
-
3-difluoromethyl-7-trifluoromethyl-1,2,3,4-tetrahydroisoquinoline radiochemical assay, inhibition constants are determined using four concentrations of phenylethanolamine as the variable substrate, and three concentrations of inhibitor Homo sapiens
0.000094
-
3-difluoromethyl-7-bromo-1,2,3,4-tetrahydroisoquinoline radiochemical assay, inhibition constants are determined using four concentrations of phenylethanolamine as the variable substrate, and three concentrations of inhibitor Homo sapiens
0.00017
-
3-difluoromethyl-7-nitro-1,2,3,4-tetrahydroisoquinoline radiochemical assay, inhibition constants are determined using four concentrations of phenylethanolamine as the variable substrate, and three concentrations of inhibitor Homo sapiens
0.0002
-
3-difluoromethyl-7-iodo-1,2,3,4-tetrahydroisoquinoline radiochemical assay, inhibition constants are determined using four concentrations of phenylethanolamine as the variable substrate, and three concentrations of inhibitor Homo sapiens
0.00025
-
3-difluoromethyl-7-(N-2,2,2-trifluoroethylaminosulfonyl)-1,2,3,4-tetrahydroisoquinoline radiochemical assay, inhibition constants are determined using four concentrations of phenylethanolamine as the variable substrate, and three concentrations of inhibitor Homo sapiens
0.00068
-
7-aminosulfonyl-3-difluoromethyl-1,2,3,4-tetrahydroisoquinoline radiochemical assay, inhibition constants are determined using four concentrations of phenylethanolamine as the variable substrate, and three concentrations of inhibitor Homo sapiens
0.0009
-
7-(N-4-chlorophenylaminosulfonyl)-3-difluoromethyl-1,2,3,4-tetrahydroisoquinoline radiochemical assay, inhibition constants are determined using four concentrations of phenylethanolamine as the variable substrate, and three concentrations of inhibitor Homo sapiens
0.0021
-
3-difluoromethyl-7-(propylaminosulfonyl)-1,2,3,4-tetrahydroisoquinoline radiochemical assay, inhibition constants are determined using four concentrations of phenylethanolamine as the variable substrate, and three concentrations of inhibitor Homo sapiens
0.0031
-
3-difluoromethyl-7-cyano-1,2,3,4-tetrahydroisoquinoline radiochemical assay, inhibition constants are determined using four concentrations of phenylethanolamine as the variable substrate, and three concentrations of inhibitor Homo sapiens
0.0032
-
3-difluoromethyl-7-(ethylaminosulfonyl)-1,2,3,4-tetrahydroisoquinoline radiochemical assay, inhibition constants are determined using four concentrations of phenylethanolamine as the variable substrate, and three concentrations of inhibitor Homo sapiens
0.0034
-
3-difluoromethyl-1,2,3,4-tetrahydroisoquinoline radiochemical assay, inhibition constants are determined using four concentrations of phenylethanolamine as the variable substrate, and three concentrations of inhibitor Homo sapiens
0.0053
-
3-difluoromethyl-7-(N-3-methoxypropylaminosulfonyl)-1,2,3,4-tetrahydroisoquinoline radiochemical assay, inhibition constants are determined using four concentrations of phenylethanolamine as the variable substrate, and three concentrations of inhibitor Homo sapiens
0.0056
-
7-(N-butylaminosulfonyl)-3-difluoromethyl-1,2,3,4-tetrahydroisoquinoline radiochemical assay, inhibition constants are determined using four concentrations of phenylethanolamine as the variable substrate, and three concentrations of inhibitor Homo sapiens
0.006
-
3-difluoromethyl-7-methylsulfonyl-1,2,3,4-tetrahydroisoquinoline radiochemical assay, inhibition constants are determined using four concentrations of phenylethanolamine as the variable substrate, and three concentrations of inhibitor Homo sapiens
0.037
-
3-difluoromethyl-7-(N-4-nitrophenylaminosulfonyl)-1,2,3,4-tetrahydroisoquinoline radiochemical assay, inhibition constants are determined using four concentrations of phenylethanolamine as the variable substrate, and three concentrations of inhibitor Homo sapiens