57503-02-3

Usage

InChI:InChI=1/C10H12ClNO/c1-2-8-5-3-4-6-9(8)12-10(13)7-11/h3-6H,2,7H2,1H3,(H,12,13)

Upstream product

• 578-54-1 ortho-ethylaniline 
• 79-04-9 chloroacetyl chloride 

Downstream Products

• 100316-70-9 N,N-dimethyl-glycine-(2-ethyl-anilide) 
• 1369321-44-7 2-(5,7-dimethyl-2-oxothiazolo[4,5-b]pyridin-3-yl)-N-(2-ethylphenyl)acetamide 
• 1427330-22-0 C₂₆H₂₆N₃O₂PS₃ 
• 592546-13-9 C₁₉H₂₁N₃O₂S 
• 1447585-73-0 N-(4-bromophenyl)-2-{2-[(4-bromophenyl)amino]-2-oxoethyl}-4-({2-[(2-ethylphenyl)amino]-2-oxoethyl}thio)pyrimidine-5-carboxamide 
• 1223232-39-0 C₁₂H₁₄N₄O 
• 1263764-74-4 C₁₃H₁₅N₃O 

Relevant academic research and scientific papers

Carbamylmethyl Mercaptoacetate Thioether: A Novel Scaffold for the Development of L1 Metallo-β-lactamase Inhibitors

Given the clinical importance of metallo-β-lactamases (MβLs), a new scaffold, N-substituted carbamylmethyl mercaptoacetate thioether, was constructed. The obtained molecules 1-16 inhibited MβLs from all three subclasses, but preferentially L1 from subclass B3. Compound 9 with a p-carboxyphenyl substituent exhibited the broadest spectrum with at least 70% inhibition of enzymes from all subclasses at 100 μM, while compound 5 with a p-methylphenyl substituent was the most potent inhibitor of any individual enzyme, with 97% inhibition at 100 μM and an IC50 value of 0.41 μM against L1. Isothermal titration calorimetry assays corroborate findings from UV-vis spectrophotometric assays that the inhibition of L1 by 5 is dose-dependent. Docking studies suggest that the carboxyl group, the sulfide atom, and the carbonyl group of the carbamyl coordinate Zn2 in a chelating fashion. Using E. coli cells expressing L1, 6 and 8 were able to decrease cefazolin minimum inhibitory concentration 8-fold.

Triazolylthioacetamide: A Valid Scaffold for the Development of New Delhi Metallo-β-Lactmase-1 (NDM-1) Inhibitors

The metallo-β-lactamases (MβLs) cleave the β-lactam ring of β-lactam antibiotics, conferring resistance against these drugs to bacteria. Twenty-four triazolylthioacetamides were prepared and evaluated as inhibitors of representatives of the three subclasses of MβLs. All these compounds exhibited specific inhibitory activity against NDM-1 with an IC50 value range of 0.15-1.90 μM, but no activity against CcrA, ImiS, and L1 at inhibitor concentrations of up to 10 μM. Compounds 4d and 6c are partially mixed inhibitors with Ki values of 0.49 and 0.63 μM using cefazolin as the substrate. Structure-activity relationship studies reveal that replacement of hydrogen on the aromatic ring by chlorine, heteroatoms, or alkyl groups can affect bioactivity, while leaving the aromatic ring of the triazolylthiols unmodified maintains the inhibitory potency. Docking studies reveal that the typical potent inhibitors of NDM-1, 4d and 6c, form stable interactions in the active site of NDM-1, with the triazole bridging Zn1 and Zn2, and the amide interacting with Lys 211 (Lys224).