714249-31-7

Upstream product

• 223786-22-9 1-methyl-4-(4-nitro-phenyl)-[1,4]-diazepane 
• 219132-82-8 4-(4-methyl-[1,4]-diazepan-1-yl)-aniline 
• 441313-14-0 4-(4-aminophenyl)-[1,4]-diazepane-1-carboxylic acid tert-butyl ester 
• 112275-50-0 tert-butyl 1,4-diazepine-1-carboxylate 
• 350-46-9 4-Fluoronitrobenzene 
• 50-00-0 formaldehyd 
• 55896-93-0 ethyl 2-(chlorosulfonyl)acetate 
• 771584-73-7 7-({[4-(4-methyl-1,4-diazepan-1-yl)phenyl]amino}methyl)-2-naphthonitrile 
• 4318-37-0 1-Methylhomopiperazine 
• 220220-32-6 tert-butyl 4-(4-{[(7-cyano-2-naphthyl)methyl]amino}phenyl)-1,4-diazepane-1-carboxylate 
• 220220-23-5 tert-butyl 4-(4-nitrophenyl)-1,4-diazepane-1-carboxylate 
• 286430-88-4 tert-butyl 4-(4-{[(7-cyano-2-napthyl)methyl][(2-ethoxy-2-oxoethyl)sulfonyl]amino}phenyl)-1,4-diazepane-1-carboxylate 

Relevant academic research and scientific papers

Orally active factor Xa inhibitor: Synthesis and biological activity of masked amidines as prodrugs of novel 1,4-diazepane derivatives

To improve their anticoagulant activity after oral administration, prodrug strategy was applied to fXa inhibitors based on a 1,4-diazepane template by conversion of the amidine group into amidoxime and alkoxycarbonyloxyamidine groups. This study revealed that amidoxime prodrugs bearing an ester moiety are efficient for the expression of oral anticoagulant activity. Factor Xa (fXa) is a serine protease, which plays a pivotal role in the coagulation cascade. To improve the oral anticoagulant activity of fXa inhibitors containing a 1,4-diazepane moiety as the P4 part, a prodrug strategy was examined. Among the compounds evaluated in this study, amidoxime prodrugs bearing an ester moiety, such as compounds 21 and 30, showed effective oral anticoagulant activity in mice.

Synthesis and biological activity of novel 1,4-diazepane derivatives as factor Xa inhibitor with potent anticoagulant and antithrombotic activity

Factor Xa (fXa) is a serine protease involved in the coagulation cascade, which has received great interest as a potential target for the development of new antithrombotic drugs. Herein we report a novel series of fXa inhibitors in which the 1,4-diazepane moiety was designed to interact with the S4 aryl-binding domain of the fXa active site. Compound 13 (YM-96765) showed potent fXa inhibitory activity (IC50=6.8nM) and effective antithrombotic activity without prolonging bleeding time.