217081-36-2

Upstream product

• 591-35-5 3,5-dichlorophenol 
• 176770-19-7 chloride of 6-chloromethyl-2-oxo-2H-1-benzopyran-3-carboxylic acid 
• 89-95-2 2-methyl-benzyl alcohol 
• 176770-22-2 6-(hydroxymethyl)-2-oxo-2H-1-benzopyran-3-carboxylic acid 
• 74901-08-9 5-hydroxymethylsalicylaldehyde 
• 176770-20-0 6-hydroxymethyl-2-oxo-2H-1-benzopyran-3-carboxylic acid ethyl ester 

Relevant academic research and scientific papers

3,6-Disubstituted coumarins as mechanism-based inhibitors of thrombin and factor Xa

In this work, coumarins were screened on thrombin (THR) and factor Xa (FXa), two of the most promising targets for the development of anticoagulant drugs. This allowed us to highlight compound 30, characterized by a 2,5-dichlorophenyl ester in the 3-position and a chloromethyl moiety in the 6-position, as a very potent THR inhibitor (ki/KI = 37 000 M-1 s-1). Moreover, this compound exhibits good selectivity over FXa (168-fold) and trypsin (54-fold). The mechanism of inactivation was investigated in this series and significantly differs from that previously observed with α-chymotrypsin. Indeed, the addition of hydrazine on the THR-inhibitor complex promotes a partial induced THR reactivation. This reactivation, confirmed by LC/MS, showed the resurgence of the native THR and a new dihydrazide complex. Docking experiments were then efficiently used to explain the trends observed in the enzymatic assays as well as to corroborate the postulated inhibition mechanism. Finally, the cell permeability of our derivatives was estimated using a computational approach.

COUMARIN DERIVATIVES, METHODS OF PREPARATION AND APPLICATION AND APPLICATION AS MEDICINES

The invention concerns compounds of general formula (I) in which: X, X' and X" independently of each other represent O or S; Y represents O, S, NH or NHS; R 3 represents in particular a cycloalkyl group; R 5, R 6, R 7 and R 8 mutually identical or different, represent in particular hydrogen; a halogen atom. Said compounds can be used as active substances of medicines as inhibitors of protease. "

Coumarinic derivatives as mechanism-based inhibitors of α-chymotrypsin and human leukocyte elastase

Novel coumarinic derivatives were synthesized and tested for their inhibitory potency toward α-CT and HLE. Cycloalkyl esters and amides were found to be essentially inactive on both enzymes. On the opposite, aromatic esters strongly inactivated α-CT where