852233-84-2

Upstream product

• 852233-83-1 ethyl 2-[(4-cyanobenzyl)oxy]-4-methyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-7-carboxylate 
• 87081-52-5 ethyl 4-amino-3-hydroxybenzoate 
• 717-01-1 ethyl 3-hydroxy-4-nitro-benzoate 
• 619-14-7 3-hydroxy-4-nitro-benzoic acid 
• 852233-80-8 ethyl 4-[(2,2-dichloroacetyl)amino]-3-hydroxybanzoate 
• 852233-82-0 ethyl 2-hydroxy-4-methyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-7-carboxylate 
• 852233-79-5 ethyl 2-hydroxy-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-7-carboxylate 

Downstream Products

• 1056736-79-8 ethyl 3-[2-(4-cyanobenzyloxy)-4-methyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-7-carbonylamino]proanoate 

Relevant academic research and scientific papers

Ring opening of 2-(benzylamino)-2H-1,4-benzoxazin-3(4H)-ones and 2-bromo-2H-1,4-benzoxazin-3(4H)-ones

Substituted 2-(benzylamino)-2H-1,4-benzoxazin-3(4H)-ones are unstable under alkaline and acidic conditions, undergoing opening of the benzoxazinone ring. 2-Bromo-2H-1,4-benzoxazin-3(4H)-ones show similar degradation under alkaline conditions, while replacement of Br at C(2) to give 2-hydroxy-2H-1,4-benzoxazin- 3(4H)-ones was observed only under mild alkaline conditions. Mechanisms of ring opening and degradation to 2-aminophenol derivatives are proposed.

3,4-Dihydro-2H-1,4-benzoxazine derivatives combining thrombin inhibitory and glycoprotein IIb/IIIa receptor antagonistic activity as a novel class of antithrombotic compounds with dual function

3,4-Dihydro-2H-1,4-benzoxazine derivatives possessing both thrombin inhibitory and glycoprotein IIb/IIIa (GPIIb/IIIa) receptor antagonistic activities were obtained by combining mimetics of the D-Phe-Pro-Arg pharmacophore of thrombin inhibitors and the Arg-Gly-Asp pharmacophore of GPIIb/IIIa receptor antagonists in the same low molecular weight peptidomimetic compound. Systematic variation of the position of substituents around the 3,4-dihydro-2H-1,4-benzoxazine nucleus, the distance between the carboxylate and amidine moieties, together with additional substituents to fill the thrombin S2 and S3 pockets resulted in compounds displaying submicromolar inhibition constants (Ki) for thrombin and submicromolar IC50 for inhibition of binding of fibrinogen to platelet GPIIb/IIIa receptor. Some of these compounds, such as 17a, 17b, 17d, and 17h possessing a well balanced activity at both targets, are a good starting point for further optimization. Incorporation of anticoagulant and platelet antiaggregatory activity in the same molecule constitutes a promising approach toward novel antithrombotic agents.

Toward a novel class of antithrombotic compounds with dual function. Discovery of 1,4-benzoxazin-3(4H)-one derivatives possessing thrombin inhibitory and fibrinogen receptor antagonistic activities

A novel class of potential antithrombotic compounds with moderate thrombin inhibitory and fibrinogen receptor antagonistic activity is described. Combination of anticoagulant and antiaggregatory activity in the same molecular entity is presented as a new

ANTITHROMBOTIC COMPOUNDS WITH DUAL FUNCTION

The present invention comprises compounds of the general formula (I) : and pharmaceutically acceptable salts thereof, wherein the substituents have in the description specified meaning. The compounds are used as antithrombotic agents possessing inhibitory