15745-94-5

Upstream product

• 62-53-3 aniline 
• 54505-72-5 diethylmalonyl chloride 

Downstream Products

• 59116-40-4 5,5-diethyl-2-methoxy-3-phenyl-oxazolidin-4-one 
• 39031-15-7 2-Ethyl-2-methoxy-N-phenyl-butyramide 
• 15724-92-2 3-Oxy-3,3-diphenyl-2,2-diethyl-propionsaeureanilid 
• 6832-96-8 2-ethyl-N-phenylbutanamide 
• 27166-57-0 2,2-diethyl-N-phenyl-malonamic acid 

Relevant academic research and scientific papers

4-Oxo-β-lactams (azetidine-2,4-diones) are potent and selective inhibitors of human leukocyte elastase

Human leukocyte elastase (HLE) is a serine protease stored in and secreted from neutrophils that plays a determinant role in the pathogenesis of several lung diseases. 4-Oxo-β-lactams, previously reported as acylating agents of porcine pancreatic elastase, were found to be selective and potent inhibitors of HLE. Structure - activity relationship analysis showed that inhibitory activity is very sensitive to the nature of C-3 substituents, with small alkyl substituents such as a gem-diethyl group improving the inhibitory potency when compared to gem-methyl benzyl or ethyl benzyl counterparts. 4-Oxo-β-lactams containing a heteroarylthiomethyl group on the para position of an N 1-aryl moiety afforded highly potent and selective inhibition of HLE, even at a very low inhibitor to enzyme ratio, as shown by the kon value of 3.24 x 106 M-1 s-1 for 6f. The corresponding ortho isomers were 40- to 90-fold less potent.

Azetidine-2,4-diones (4-oxo-β-lactams) as scaffolds for designing elastase inhibitors

A new class of inhibitors 4-oxo-β-lactams (azetidine-2,4-diones), containing the required structural elements for molecular recognition, inhibit porcine pancreatic elastase (PPE) but show a dramatically lower reactivity toward hydroxide compared with the analogous inhibitors 3-oxo-β-sultams. Inhibition is the result of acylation of the active site serine and electron-withdrawing substituents at the N-(4-aryl) position in 3,3-diethyl-N-aryl derivatives increasing the rate of enzyme acylation and generating a Hammett ρ-value of 0.65. Compared with a ρ-value of 0.96 for the rates of alkaline hydrolysis of the same series, this is indicative of an earlier transition state for the enzyme-catalyzed reaction. Docking studies indicate favorable noncovalent interactions of the inhibitor with the enzyme. Compound 2i, the most potent inhibitor against PPE, emerged as a very potent HLE inhibitor, with a second-order rate for enzyme inactivation of ～5 × 105 M-1 s-1.