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Literature summary for 3.4.23.46 extracted from

  • Hamada, Y.; Ohta, H.; Miyamoto, N.; Yamaguchi, R.; Yamani, A.; Hidaka, K.; Kimura, T.; Saito, K.; Hayashi, Y.; Ishiura, S.; Kiso, Y.
    Novel non-peptidic and small-sized BACE1 inhibitors (2008), Bioorg. Med. Chem. Lett., 18, 1643-1647.
    View publication on PubMed

Application

Application Comment Organism
pharmacology design of inhibitor drugs for treatment of Alzheimer disease Homo sapiens

Crystallization (Commentary)

Crystallization (Comment) Organism
conformational study of BACE1 inhibitor, molecular surface model and stereoview indicated Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
2-[[(1S,2S)-1-benzyl-2-hydroxy-3-oxo-3-[[3-(2H-tetrazol-5-yl)phenyl]amino]propyl]carbamoyl]-6-[[(4S)-4-phenyl-1,3-oxazolidin-3-yl]carbonyl]pyridin-4-yl methanesulfonate i.e. KMI-1036, BACE1 inhibitors with a 5-membered ring at the P3 position and their BACE1 inhibitory activities summarized Homo sapiens
3-[(2H-tetrazol-5-ylcarbonyl)amino]-L-alanyl-L-valyl-N-((1S,2R)-1-benzyl-3-[(3,5-di-2H-tetrazol-5-ylphenyl)amino]-2-hydroxy-3-oxopropyl)-L-leucinamide i.e. KMI-684, beta-secretase inhibitors with a hydroxymethylcarbonyl (HMC) isostere, inihbitory activities optimized Homo sapiens
3-[(2H-tetrazol-5-ylcarbonyl)amino]-L-alanyl-L-valyl-N-((1S,2R)-1-benzyl-3-[(3,5-dicarboxyphenyl)amino]-2-hydroxy-3-oxopropyl)-L-leucinamide i.e. KMI-429, beta-secretase inhibitors with a hydroxymethylcarbonyl (HMC) isostere, inihbitory activities optimized Homo sapiens
3-[(2H-tetrazol-5-ylcarbonyl)amino]-L-alanyl-L-valyl-N-((1S,2R)-1-benzyl-3-[(3-carboxyphenyl)amino]-2-hydroxy-3-oxopropyl)-L-leucinamide i.e. KMI-420, beta-secretase inhibitors with a hydroxymethylcarbonyl (HMC) isostere, inihbitory activities optimized Homo sapiens
3-[(2H-tetrazol-5-ylcarbonyl)amino]-L-alanyl-L-valyl-N-[(1S,2R)-1-benzyl-2-hydroxy-3-oxo-3-([3-(2H-tetrazol-5-yl)phenyl]amino)propyl]-L-leucinamide i.e. KM-570, beta-secretase inhibitors with a hydroxymethylcarbonyl (HMC) isostere, inihbitory activities optimized Homo sapiens
additional information isophthalic-type aromatic residues at the P2 position and an HMC isostere at the P1 position used as lead compounds for generation of novel inhibitors against beta-secretase BACE1, development of novel inhibitors against beta-secretase BACE1 studied, novel nonpeptidic and small-sized BACE1 inhibitors possessing a 2,6-pyridinedicarboxylic, chelidamic or chelidonic residue at the P2 position described, inhibitory activities summarized Homo sapiens
N-[(1S,2S)-1-benzyl-2-hydroxy-3-oxo-3-[[3-(2H-tetrazol-5-yl)phenyl]amino]propyl]-4-oxo-6-[[(4S)-4-phenyl-1,3-oxazolidin-3-yl]carbonyl]-1,4-dihydropyridine-2-carboxamide i.e. KMI-1030, BACE1 inhibitors with a 5-membered ring at the P3 position and their BACE1 inhibitory activities summarized Homo sapiens
N-[(1S,2S)-1-benzyl-2-hydroxy-3-oxo-3-[[3-(2H-tetrazol-5-yl)phenyl]amino]propyl]-4-oxo-6-[[(4S)-4-phenyl-1,3-oxazolidin-3-yl]carbonyl]-4H-pyran-2-carboxamide i.e. KMI-1027, BACE1 inhibitors with a 5-membered ring at the P3 position and their BACE1 inhibitory activities summarized Homo sapiens
N-[(1S,2S)-1-benzyl-2-hydroxy-3-oxo-3-[[3-(2H-tetrazol-5-yl)phenyl]amino]propyl]-6-[[(4S)-4-phenyl-1,3-oxazolidin-3-yl]carbonyl]pyridine-2-carboxamide i.e. KMI-1023, BACE1 inhibitors with a 5-membered ring at the P3 position and their BACE1 inhibitory activities summarized Homo sapiens

Organism

Organism UniProt Comment Textmining
Homo sapiens P56817
-
-

Specific Activity [micromol/min/mg]

Specific Activity Minimum [µmol/min/mg] Specific Activity Maximum [µmol/min/mg] Comment Organism
additional information
-
synthesis, structure and potencies of BACE1 inhibitors shown, inhibitory assays summarized, novel nonpeptidic and small-sized BACE1 inhibitors developed, design of small-sized BACE1 inhibitor 2 possessing heterocyclic ring at the P2 position shown, reagents and conditions summarized, BACE1 inhibitors possessing benzylamino-type groups at the P3 position and their BACE1 inhibitory activities summarized, BACE1 inhibitors with a 5-membered ring at the P3 position and inhibitory activities indicated, molecular surface properties shown Homo sapiens

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
additional information synthesis, structure and potencies of beta-secretase BACE1 inhibitors optimized, in vivo enzymatic stability and permeability across the blood-brain barrier of penta-peptidic inhibitors analyzed, stereoview and molecular surface properties shown, reagents and conditions summarized Homo sapiens ?
-
?

Synonyms

Synonyms Comment Organism
BACE1
-
Homo sapiens
beta-secretase
-
Homo sapiens

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
additional information
-
beta-secretase inhibitors with a hydroxymethylcarbonyl (HMC) isostere used as a substrate transition-state mimic, potent BACE1 inhibitory activities of about 0.0012 mM IC50 shown, BACE1 inhibitors with a 5-membered ring at the P3 position and their BACE1 inhibitory activities summarized Homo sapiens additional information
0.0012
-
i.e. KMI-684, used as a substrate transition-state mimic Homo sapiens 3-[(2H-tetrazol-5-ylcarbonyl)amino]-L-alanyl-L-valyl-N-((1S,2R)-1-benzyl-3-[(3,5-di-2H-tetrazol-5-ylphenyl)amino]-2-hydroxy-3-oxopropyl)-L-leucinamide
0.0039
-
i.e. KMI-429, used as a substrate transition-state mimic Homo sapiens 3-[(2H-tetrazol-5-ylcarbonyl)amino]-L-alanyl-L-valyl-N-((1S,2R)-1-benzyl-3-[(3,5-dicarboxyphenyl)amino]-2-hydroxy-3-oxopropyl)-L-leucinamide
0.0048
-
i.e. KMI-570, used as a substrate transition-state mimic Homo sapiens 3-[(2H-tetrazol-5-ylcarbonyl)amino]-L-alanyl-L-valyl-N-[(1S,2R)-1-benzyl-2-hydroxy-3-oxo-3-([3-(2H-tetrazol-5-yl)phenyl]amino)propyl]-L-leucinamide
0.0082
-
i.e. KMI-420, used as a substrate transition-state mimic Homo sapiens 3-[(2H-tetrazol-5-ylcarbonyl)amino]-L-alanyl-L-valyl-N-((1S,2R)-1-benzyl-3-[(3-carboxyphenyl)amino]-2-hydroxy-3-oxopropyl)-L-leucinamide
0.05
-
i.e. KMI-1027, BACE1 inhibitors with a 5-membered ring at the P3 position and their BACE1 inhibitory activities summarized Homo sapiens N-[(1S,2S)-1-benzyl-2-hydroxy-3-oxo-3-[[3-(2H-tetrazol-5-yl)phenyl]amino]propyl]-4-oxo-6-[[(4S)-4-phenyl-1,3-oxazolidin-3-yl]carbonyl]-4H-pyran-2-carboxamide
0.096
-
i.e. KMI-1036, BACE1 inhibitors with a 5-membered ring at the P3 position and their BACE1 inhibitory activities summarized Homo sapiens 2-[[(1S,2S)-1-benzyl-2-hydroxy-3-oxo-3-[[3-(2H-tetrazol-5-yl)phenyl]amino]propyl]carbamoyl]-6-[[(4S)-4-phenyl-1,3-oxazolidin-3-yl]carbonyl]pyridin-4-yl methanesulfonate
0.14
-
i.e. KMI-1023, BACE1 inhibitors with a 5-membered ring at the P3 position and their BACE1 inhibitory activities summarized Homo sapiens N-[(1S,2S)-1-benzyl-2-hydroxy-3-oxo-3-[[3-(2H-tetrazol-5-yl)phenyl]amino]propyl]-6-[[(4S)-4-phenyl-1,3-oxazolidin-3-yl]carbonyl]pyridine-2-carboxamide
0.36
-
i.e. KMI-1030, BACE1 inhibitors with a 5-membered ring at the P3 position and their BACE1 inhibitory activities summarized Homo sapiens N-[(1S,2S)-1-benzyl-2-hydroxy-3-oxo-3-[[3-(2H-tetrazol-5-yl)phenyl]amino]propyl]-4-oxo-6-[[(4S)-4-phenyl-1,3-oxazolidin-3-yl]carbonyl]-1,4-dihydropyridine-2-carboxamide