7145-38-2

Basic information

• Product Name: N-(4-methyl-1,3-thiazol-2-yl)-3-oxobutanamide
• CAS NO: 7145-38-2
• Molecular Formula: C₈H₁₀N₂O₂S
• Molecular Weight: 198.2422
• Mol File: 7145-38-2.mol
• Article Data: 1

Chemical Properties

• Density: 1.307g/cm³
• Refractive Index: 1.589
• CAS DataBase Reference: N-(4-methyl-1,3-thiazol-2-yl)-3-oxobutanamide(CAS DataBase Reference)
• NIST Chemistry Reference: N-(4-methyl-1,3-thiazol-2-yl)-3-oxobutanamide(7145-38-2)
• EPA Substance Registry System: N-(4-methyl-1,3-thiazol-2-yl)-3-oxobutanamide(7145-38-2)

Safety Data

• Hazardous Substances Data: 7145-38-2(Hazardous Substances Data)

Upstream product

• 1603-91-4 4-methylthiazol-2-ylamine 
• 141-97-9 ethyl acetoacetate 
• 5394-63-8 2,2,6-trimethyl-4H-1,3-dioxin-4-one 

Relevant articles and documents

Design and synthesis of novel 3,5-bis-N-(aryl/heteroaryl) carbamoyl-4-aryl-1,4-dihydropyridines as small molecule BACE-1 inhibitors

Alzheimer disease (AD) is a neuronal dementia for which no treatment has been consolidated yet. Major pathologic hallmark of AD is the aggregated extracellular amyloid-β plaques in the brains of disease sufferers. Aβ-peptide is a major component of amyloid plaques and is produced from amyloid precursor protein (APP) via the proteolysis action. An aspartyl protease known as β-site amyloid precursor protein cleaving enzyme (BACE-1) is responsible for this proteolytic action. Distinctive role of BACE-1 in AD pathogenesis has made it a validated target to develop anti-Alzheimer agents. Our structure-based virtual screening method led to the synthesis of novel 3,5-bis-N-(aryl/heteroaryl) carbamoyl-4-aryl-1,4-dihydropyridine BACE-1 inhibitors (6a-6p; in vitro hits). Molecular docking and DFT-based ab initio studies using B3LYP functional in association with triple-ζ basis set (TZV) proposed binding mode and binding energies of ligands in the active site of the receptor. In vitro BACE-1 inhibitory activities were determined by enzymatic fluorescence resonance energy transfer (FRET) assay. Most of the synthesized dihydropyridine scaffolds were active against BACE-1 while 6d, 6k, 6n and 6a were found to be the most potent molecules with IC50 values of 4.21, 4.27, 4.66 and 6.78 μM, respectively. Superior BACE-1 inhibitory activities were observed for dihydropyridine derivatives containing fused/nonfused thiazole containing groups, possibly attributing to the additional interactions with S2-S3 subpocket residues. Relatively reliable correlation between calculated binding energies and experimental BACE-1 inhibitory activities was achieved (R2 = 0.51). Moreover, compounds 6d, 6k, 6n and 6a exhibited relatively no calcium channel blocking activity with regard to nifedipine suggesting them as appropriate candidates for further modification(s) to BACE-1 inhibitory scaffolds.