1201686-45-4

Upstream product

• 1201687-15-1 tert-butyl 5-chloro-2-(1H-tetrazol-1-yl)benzylcarbamate 
• 32222-45-0 (R)-2-(4-fluorophenyl)-2-hydroxyacetic acid 
• 32222-45-0 4-fluoromandelic acid 
• 1201687-03-7 (R)-2-(4-fluorophenyl)-2-(trimethylsilyloxy)acetyl chloride 
• 1201687-04-8 ethyl (S)-1-((R)-2-(4-fluorophenyl)-2-hydroxyacetyl)-4,5-dihydro-1H-pyrazole-5-carboxylate 
• 1201687-05-9 (S)-1-((R)-2-(4-fluorophenyl)-2-hydroxyacetyl)-4,5-dihydro-1H-pyrazole-5-carboxylic acid 
• 449756-95-0 5-Chloro-2-tetrazol-1-yl-benzylamine 

Downstream Products

• 1201686-67-0 [(1R)-2-[(5S)-5-[[5-chloro-2-(tetrazol-1-yl)phenyl]methylcarbamoyl]-4,5-dihydropyrazol-1-yl]-1-(4-fluorophenyl)-2-oxoethyl] acetate 
• 1201686-73-8 [(1R)-2-[(5S)-5-[[5-chloro-2-(tetrazol-1-yl)phenyl]methylcarbamoyl]-4,5-dihydropyrazol-1-yl]-1-(4-fluorophenyl)-2-oxoethyl] benzoate 
• 1201686-72-7 (1R)-2-[(5S)-5-{[5-chloro-2-(1H-tetrazol-1-yl)benzyl]carbamoyl}-4,5-dihydro-1H-pyrazol-1-yl]-1-(4-fluorophenyl)-2-oxoethyl propanoate 
• 1201686-74-9 (R)-2-((S)-5-(5-chloro-2-(1H-tetrazol-1-yl)benzylcarbamoyl)-4,5-dihydro-1H-pyrazol-1-yl)-1-(4-fluorophenyl)-2-oxoethyl 3-(2,4-dimethyl-6-(propionyloxy)phenyl)-3-methylbutanoate 

Relevant academic research and scientific papers

Discovery of AZD8165 - A clinical candidate from a novel series of neutral thrombin inhibitors

A novel series of neutral thrombin inhibitors has been developed using a selection process based on docking experiments and property calculations and predictions. This work resulted in the identification of the highly potent thrombin inhibitor compound 85 (Ki = 300 pM) and the corresponding propionate prodrug 5 (AZD8165) as a candidate for clinical evaluation in the treatment of thrombosis and related diseases. AZD8165 was found to be safe and well tolerated and delivered the expected pharmacological response in a phase I trial in healthy male volunteers.

A one-pot asymmetric synthesis of a N-acylated 4,5-dihydropyrazole, a key intermediate of thrombin inhibitor AZD8165

A short, chromatography-free, and scalable synthetic route to thrombin inhibitor 1, the active metabolite of the propionic ester prodrug AZD8165, has been developed. The key synthetic step involved cycloaddition of TMS-diazomethane and ethyl acrylate to give an intermediate racemic dihydropyrazole which was reacted with enantiomerically pure 4-fluoro mandelic acid chloride in a one-pot dynamic kinetic resolution (DKR) process.

Novel Compounds 148

This invention relates to novel pharmaceutically useful compounds of formula (I), in particular compounds that are competitive inhibitors of trypsin-like serine proteases, especially thrombin, their use as medicaments, pharmaceutical compositions containi