Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary for 3.4.22.27 extracted from

  • Irie, O.; Kosaka, T.; Kishida, M.; Sakaki, J.; Masuya, K.; Konishi, K.; Yokokawa, F.; Ehara, T.; Iwasaki, A.; Iwaki, Y.; Hitomi, Y.; Toyao, A.; Gunji, H.; Teno, N.; Iwasaki, G.; Hirao, H.; Kanazawa, T.; Tanabe, K.; Hiestand, P.C.; Malcangio, M.; Fox, A.J.; Bevan, S.J.; Yaqoob, M.; Culshaw, A.J.; Hart, T.W.; Hallet, A.
    Overcoming hERG issues for brain-penetrating cathepsin S inhibitors: 2-cyanopyrimidines. Part 2 (2008), Bioorg. Med. Chem. Lett., 18, 5280-5284.
    View publication on PubMed
Search for more literature for 3.4.22.27

Application

Application Comment Organism
drug development brain-penetrating cathepsin S inhibitors demonstrate potential clinical utility for the treatment of multiple sclerosis and neuropathic pain Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
2-cyano-4-(2-hydroxyethoxy)-N-methyl-6-[(spiro[3.5]non-7-ylmethyl)amino]pyrimidine-5-carboxamide brain-penetrating cathepsin S inhibitors Homo sapiens
2-cyano-4-[(1,4-dioxaspiro[4.5]dec-8-ylmethyl)amino]-N-methyl-6-[(1-methylpiperidin-4-yl)methoxy]pyrimidine-5-carboxamide brain-penetrating cathepsin S inhibitors Homo sapiens
2-cyano-4-[(2-cyclopentylethyl)amino]-N-methyl-6-[(1-methylpiperidin-4-yl)methoxy]pyrimidine-5-carboxamide brain-penetrating cathepsin S inhibitors Homo sapiens
2-cyano-4-[(6,8-dioxaspiro[3.5]non-7-ylmethyl)amino]-N-methyl-6-[(1-methylpiperidin-4-yl)methoxy]pyrimidine-5-carboxamide brain-penetrating cathepsin S inhibitors Homo sapiens
2-cyano-4-[[1-(2-hydroxyethyl)piperidin-4-yl]methoxy]-N-methyl-6-[(spiro[3.5]non-7-ylmethyl)amino]pyrimidine-5-carboxamide brain-penetrating cathepsin S inhibitors Homo sapiens
2-cyano-N-methyl-4-(piperidin-4-ylmethoxy)-6-[(spiro[3.5]non-7-ylmethyl)amino]pyrimidine-5-carboxamide brain-penetrating cathepsin S inhibitors Homo sapiens
2-cyano-N-methyl-4-[(1-methylpiperidin-4-yl)methoxy]-6-[(spiro[3.5]non-7-ylmethyl)amino]pyrimidine-5-carboxamide brain-penetrating cathepsin S inhibitors Homo sapiens
2-cyano-N-methyl-4-[(1-methylpiperidin-4-yl)methoxy]-6-[(spiro[4.5]dec-8-ylmethyl)amino]pyrimidine-5-carboxamide brain-penetrating cathepsin S inhibitors Homo sapiens
2-cyano-N-methyl-4-[(spiro[3.5]non-7-ylmethyl)amino]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyrimidine-5-carboxamide brain-penetrating cathepsin S inhibitors Homo sapiens
2-cyano-N-methyl-4-[2-(1-methylpiperidin-4-yl)ethoxy]-6-[(spiro[2.5]oct-6-ylmethyl)amino]pyrimidine-5-carboxamide brain-penetrating cathepsin S inhibitors Homo sapiens
2-cyano-N-methyl-4-[2-(1-methylpiperidin-4-yl)ethoxy]-6-[(spiro[3.5]non-7-ylmethyl)amino]pyrimidine-5-carboxamide brain-penetrating cathepsin S inhibitors Homo sapiens
2-cyano-N-methyl-4-[[1-(1-methylethyl)piperidin-4-yl]methoxy]-6-[(spiro[3.5]non-7-ylmethyl)amino]pyrimidine-5-carboxamide brain-penetrating cathepsin S inhibitors Homo sapiens
4-[(1-acetylpiperidin-4-yl)methoxy]-2-cyano-N-methyl-6-[(spiro[3.5]non-7-ylmethyl)amino]pyrimidine-5-carboxamide brain-penetrating cathepsin S inhibitors Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
additional information Homo sapiens in antigen presenting cells Cat S plays an essential role in the proteolytic events that lead to antigen presentation at the cells surface for recognition by T cells ?
-
 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens P25774
-
-

Source Tissue

Source Tissue Comment Organism Textmining
B-lymphocyte
-
 Homo sapiens
-
dendritic cell
-
 Homo sapiens
-
macrophage
-
 Homo sapiens
-
microglia
-
 Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
additional information in antigen presenting cells Cat S plays an essential role in the proteolytic events that lead to antigen presentation at the cells surface for recognition by T cells Homo sapiens ?
-
 ?
Z-Leu-Leu-Arg-7-amido-4-methylcoumarin + H2O
-
 Homo sapiens Z-Leu-Leu-Arg + 7-amino-4-methylcoumarin
-
 ?

Synonyms

Synonyms Comment Organism
cathepsin S
-
 Homo sapiens
CatS
-
 Homo sapiens

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
additional information
-
 IC50 is above 0.001 mM, determined by a fluorometric assay with recombinant catS employing L-Leu-Leu-Arg-7-amido-4-methylcoumarin as synthetic substrate Homo sapiens 2-cyano-4-[(6,8-dioxaspiro[3.5]non-7-ylmethyl)amino]-N-methyl-6-[(1-methylpiperidin-4-yl)methoxy]pyrimidine-5-carboxamide
0.000002
-
 determined by a fluorometric assay with recombinant catS employing L-Leu-Leu-Arg-7-amido-4-methylcoumarin as synthetic substrate Homo sapiens 2-cyano-N-methyl-4-[2-(1-methylpiperidin-4-yl)ethoxy]-6-[(spiro[2.5]oct-6-ylmethyl)amino]pyrimidine-5-carboxamide
0.000003
-
 determined by a fluorometric assay with recombinant catS employing L-Leu-Leu-Arg-7-amido-4-methylcoumarin as synthetic substrate Homo sapiens 2-cyano-N-methyl-4-[(1-methylpiperidin-4-yl)methoxy]-6-[(spiro[3.5]non-7-ylmethyl)amino]pyrimidine-5-carboxamide
0.000003
-
 determined by a fluorometric assay with recombinant catS employing L-Leu-Leu-Arg-7-amido-4-methylcoumarin as synthetic substrate Homo sapiens 2-cyano-N-methyl-4-[(1-methylpiperidin-4-yl)methoxy]-6-[(spiro[4.5]dec-8-ylmethyl)amino]pyrimidine-5-carboxamide
0.000003
-
 determined by a fluorometric assay with recombinant catS employing L-Leu-Leu-Arg-7-amido-4-methylcoumarin as synthetic substrate Homo sapiens 2-cyano-N-methyl-4-[[1-(1-methylethyl)piperidin-4-yl]methoxy]-6-[(spiro[3.5]non-7-ylmethyl)amino]pyrimidine-5-carboxamide
0.000003
-
 determined by a fluorometric assay with recombinant catS employing L-Leu-Leu-Arg-7-amido-4-methylcoumarin as synthetic substrate Homo sapiens 2-cyano-4-[[1-(2-hydroxyethyl)piperidin-4-yl]methoxy]-N-methyl-6-[(spiro[3.5]non-7-ylmethyl)amino]pyrimidine-5-carboxamide
0.000004
-
 determined by a fluorometric assay with recombinant catS employing L-Leu-Leu-Arg-7-amido-4-methylcoumarin as synthetic substrate Homo sapiens 2-cyano-N-methyl-4-[2-(1-methylpiperidin-4-yl)ethoxy]-6-[(spiro[3.5]non-7-ylmethyl)amino]pyrimidine-5-carboxamide
0.000005
-
 determined by a fluorometric assay with recombinant catS employing L-Leu-Leu-Arg-7-amido-4-methylcoumarin as synthetic substrate Homo sapiens 2-cyano-N-methyl-4-[(spiro[3.5]non-7-ylmethyl)amino]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyrimidine-5-carboxamide
0.000005
-
 determined by a fluorometric assay with recombinant catS employing L-Leu-Leu-Arg-7-amido-4-methylcoumarin as synthetic substrate Homo sapiens 2-cyano-N-methyl-4-(piperidin-4-ylmethoxy)-6-[(spiro[3.5]non-7-ylmethyl)amino]pyrimidine-5-carboxamide
0.000006
-
 determined by a fluorometric assay with recombinant catS employing L-Leu-Leu-Arg-7-amido-4-methylcoumarin as synthetic substrate Homo sapiens 2-cyano-4-(2-hydroxyethoxy)-N-methyl-6-[(spiro[3.5]non-7-ylmethyl)amino]pyrimidine-5-carboxamide
0.00001
-
 determined by a fluorometric assay with recombinant catS employing L-Leu-Leu-Arg-7-amido-4-methylcoumarin as synthetic substrate Homo sapiens 4-[(1-acetylpiperidin-4-yl)methoxy]-2-cyano-N-methyl-6-[(spiro[3.5]non-7-ylmethyl)amino]pyrimidine-5-carboxamide
0.000026
-
 determined by a fluorometric assay with recombinant catS employing L-Leu-Leu-Arg-7-amido-4-methylcoumarin as synthetic substrate Homo sapiens 2-cyano-4-[(2-cyclopentylethyl)amino]-N-methyl-6-[(1-methylpiperidin-4-yl)methoxy]pyrimidine-5-carboxamide
0.000031
-
 determined by a fluorometric assay with recombinant catS employing L-Leu-Leu-Arg-7-amido-4-methylcoumarin as synthetic substrate Homo sapiens 2-cyano-4-[(1,4-dioxaspiro[4.5]dec-8-ylmethyl)amino]-N-methyl-6-[(1-methylpiperidin-4-yl)methoxy]pyrimidine-5-carboxamide