213749-64-5Relevant academic research and scientific papers
Synthesis, evaluation and structure-activity relationship of new 3-carboxamide coumarins as FXIIa inhibitors
Bouckaert, Charlotte,Serra, Silvia,Rondelet, Grégoire,Dolu?i?, Eduard,Wouters, Johan,Dogné, Jean-Michel,Frédérick, Rapha?l,Pochet, Lionel
, p. 181 - 194 (2016/05/02)
Inhibitors of the coagulation factor XIIa (FXIIa) are attractive to detail the roles of this protease in hemostasis and thrombosis, to suppress artifact due to contact pathway activation in blood coagulation assays, and they are promising as antithrombotic therapy. The 3-carboxamide coumarins have been previously described as small-molecular-weight FXIIa inhibitors. In this study, we report a structure-activity relationship (SAR) study around this scaffold with the aim to discover new selective FXIIa inhibitors with an improved physico-chemical profile. To better understand these SAR, docking experiments were undertaken. For this purpose, we built an original hybrid model of FXIIa. This model has the advantage to gather the best features from the recently published crystal structure of FXIIa in its zymogen form and a more classical homology model. Results with the hybrid model are encouraging as they help understanding the activity and selectivity of our best compounds.
Synthesis and selective human monoamine oxidase inhibition of 3-carbonyl, 3-acyl, and 3-carboxyhydrazido coumarin derivatives
Secci, Daniela,Carradori, Simone,Bolasco, Adriana,Chimenti, Paola,Yá?ez, Matilde,Ortuso, Francesco,Alcaro, Stefano
, p. 4846 - 4852 (2011/11/13)
Several 3-carbonyl (1-26), 3-acyl (27-52), and 3-carboxyhydrazido (53-58) coumarins have been synthesized in high yields (72-99%) and tested in vitro for their human monoamine oxidase A and B (hMAO-A and hMAO-B) inhibitory activity. Different substituents on the coumarin nucleus were evaluated for their effect on biological activity and isoform selectivity. Substitution at position C7 of the 3-ethyl ester coumarin ring, or the introduction of a hydrazido substituent at C3, were important to obtain highly potent and selective hMAO-B inhibitors with IC50 values in the nanomolar range. Some derivatives were also submitted to a stability test and showed no chemical cleavage in vitro.
Solid phase synthesis of substituted coumarin-3-carboxylic acids via the Knoevenagel condensation
Watson, Brett T.,Christiansen, Gerda E.
, p. 6087 - 6090 (2007/10/03)
A solid phase synthesis of substituted coumarin-3-carboxylates using the Knoevenagel condensation reaction between ethyl malonate bound to the Wang resin and ortho-hydroxyarylaldehydes is described. The reaction has been shown to proceed cleanly to give the desired products.
