217313-86-5

Upstream product

• 501-53-1 benzyl chloroformate 
• 17201-43-3 4-cyanobenzyl bromide 
• 51779-32-9 iminodicarboxylic acid di-tert-butyl ester 
• 510772-07-3 4-di-tert-butoxycarbonylaminomethyl-N-hydroxy-benzamidine 
• 172348-74-2 tert-butyl ((tert-butoxycarbonyl)(4-cyanobenzyl)amino)-methanoate 

Downstream Products

• 162694-63-5 melagatran 
• 756465-76-6 C₁₈H₁₉N₃O₂ 
• 308846-55-1 C₂₈H₃₅N₃O₆ 
• 308846-53-9 C₂₀H₂₉N₃O₄ 
• 217313-84-3 C₁₈H₂₇N₃O₄ 
• 172348-75-3 [(4-aminomethyl-phenyl)-imino-methyl]-carbamic acid benzyl ester dihydrochloride 

Relevant academic research and scientific papers

Enhancement of hydrophobic interactions and hydrogen bond strength by cooperativity: Synthesis, modeling, and molecular dynamics simulations of a congeneric series of thrombin inhibitors

Accurately predicting the binding affinity of ligands to their receptors by computational methods is one of the major challenges in structure-based drug design. One of the potentially significant errors in these predictions is the common assumption that the ligand binding affinity contributions of noncovalent interactions are additive. Herein we present data obtained from two separate series of thrombin inhibitors containing hydrophobic side chains of increasing size that bind in the S3 pocket and with, or without, an adjacent amine that engages in a hydrogen bond with Gly 216. The first series of inhibitors has a m-chlorobenzyl moiety binding in the S1 pocket, and the second has a benzamidine moiety. When the adjacent hydrogen bond is present, the enhanced binding affinity per ?2 of hydrophobic contact surface in the S3 pocket improves by 75% and 59%, respectively, over the inhibitors lacking this hydrogen bond. This improvement of the binding affinity per ?2 demonstrates cooperativity between the hydrophobic interaction and the hydrogen bond.

Selective factor Xa inhibitors

Novel compounds, their salts and compositions related thereto having activity against mammalian factor Xa are disclosed. The compounds are useful in vitro or in vivo for preventing or treating coagulation disorders.

Large scale preparation of protected 4-aminomethylbenzamidine. Application to the synthesis of the thrombin inhibitor, melagatran

To allow the preparation of melagatran on a multigram scale, we have investigated several approaches for the synthesis of the key intermediate 4- aminomethylbenzamidine. The only industrially suitable pathway relies on the preparation of an N-hydroxyimino