791046-06-5

Upstream product

• 96-99-1 4-chloro-3-nitrobenzoate 
• 42288-26-6 (4-cyanophenyl)glycine 
• 62750-11-2 ethyl 3-phenylaminopropionate 
• 140-88-5 ethyl acrylate 
• 62-53-3 aniline 
• 211915-73-0 1-methyl-2-[N-(4-cyanophenyl)-aminomethyl]-benzimidazol-5-yl-carboxylic acid-N-phenyl-N-(2-ethoxycarbonylethyl)-amide 
• 211915-71-8 4-methylamino-3-nitro-benzoic acid-N-phenyl-N-(2-ethoxycarbonylethyl)amide 
• 211915-72-9 3-Amino-4-methylamino-benzoic acid-N-phenyl-N-(2-ethoxy-carbonylethyl)-amide 
• 41263-74-5 4-(methylamino)-3-nitrobenzoic acid 
• 82357-48-0 4-methylamino-3-nitro-benzoic acid chloride 

Relevant academic research and scientific papers

Multi-substituted 4-methyl ester derivative of amino benzonitrile trunk and its preparation and use

The invention provides new ester derivatives with a general formula (I) shown in the specification of multi-substituted 4-methylamino-benzamidine or pharmaceutically acceptable salts, wherein A1, A2, A3 and A4 in the formula are as defined in the specification. The compounds have an anticoagulant effect and can be used for preparing medicaments for preventing and treating thromboembolic diseases.

Structure-based design of novel potent nonpeptide thrombin inhibitors

The clinical syndromes of thromboembolism are evoked by an excessive stimulation of the coagulation cascade. In this context, the serine protease thrombin plays a key role. Considerable efforts have therefore been devoted to the discovery of safe, orally active inhibitors of this enzyme. On the basis of the X-ray crystal structure of the peptidelike thrombin inhibitor NAPAP complexed with bovine thrombin, we have designed a new structural class of nonpeptidic inhibitors employing a 1,2,5-trisubstituted benzimidazole as the central scaffold. Supported by a series of X-ray structure analyses, we optimized the activity of these compounds. Thrombin inhibition in the lower nanomolar range could be achieved although the binding energy mainly results from nonpolar, hydrophobic interactions. To improve in vivo potency, we increased the overall hydrophilicity of the molecules by introducing carboxylate groups. The very polar compound 24 (BIBR 953) exhibited the most favorable activity profile in vivo. This zwitterionic molecule was converted into the double-prodrug 31 (BIBR 1048), which showed strong oral activity in different animal species. On the basis of these results, 31 was chosen for clinical development.