Edoxaban: an Anticoagulant Drug

About Edoxaban

Edoxaban is an anticoagulant drug which acts as a direct factor Xa inhibitor.

Chemical name: Edoxaban;N-(5-Chloro-2-pyridinyl)-N'-[(1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-[[(4,5,6,7-tetrahydro-5-methylthiazolo[5,4-c]pyridin-2-yl)carbonyl]amino]cyclohexyl]ethanediamide;Savaysa;N1-(5-chloropyridin-2-yl)-N2-((1S,2R,4S)-4-(dimethylcarbamoyl)-2-(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamido)cyclohexyl)oxalamide;DU-176b;Lixiana;

Molecular formula: C24H30ClN7O4S

Structural formula：

Product characteristics

Edoxaban is a small molecular oral anticoagulant developed by No.1 Sankong Co., Ltd., Japan. It is a clotting factor X (FXa) blocker. In the process of coagulation, activated coagulation factor X (FXa) activates prothrombin (FII) into thrombin (FIIa), to promote fibrin formation, thus forming thrombus, so FXa has become the main target for the development of a new generation of anticoagulant drugs. Edoxaban is an oral anticoagulant to inhibit thrombosis through selective, reversible and direct inhibition of FXa. Its selectivity to FXa is 104 times higher than that of FIIa. Clinical trials at home and abroad in Japan have confirmed that this product can effectively inhibit VTE, in patients undergoing lower limb plastic surgery and is safe and reliable. 

Fibrin and red blood cells, the final products of blood coagulation, are the main body of venous thrombosis. The role of FXa is to activate prothrombin into thrombin, which converts fibrinogen into fibrin. One molecule of FXa can produce 138molecular thrombin in 1 minute. In addition to prothrombin, FXa can also activate coagulation factor V, coagulation factor VII and C protein. In vitro, this product competitively and selectively inhibits FXa, but has weak inhibitory activity on serine proteases of other related coagulation factors.

Edoxaban clinical trials were conducted in patients with total knee arthroplasty ((TKA)), total hip arthroplasty ((THA)) and hip fracture surgery ((HFS)) in Japan and Taiwan. The inhibitory effect of Edoxaban on the occurrence of VTE in each group was significantly better than that in the placebo group and equivalent to that in the enoxaparin group. There was no significant difference in the incidence of massive hemorrhage or severe bleeding in clinical significance among the treatment groups. The main adverse reactions were bleeding (positive urine occult blood, subcutaneous hemorrhage, wound bleeding, etc.), elevated γ-GTP, elevated ALT, and other adverse reactions included headache, diarrhea, rash, itching, edema, fever and so on. The results of safety experiments showed that Edoxaban had little effect on central nervous system, cardiovascular system, respiratory system and renal function.

Synthetic route diagram

List of Intermediates

CAS No.：1210348-34-7 

tert-Butyl [(1R,2S,5S)-2-amino-5-[(dimethylamino)carbonyl]cyclohexyl]carbamate oxalate

CAS No.: 720720-96-7

5-Methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxylic acid hydrochloride

CAS No.: 1243308-37-3

2-[(5-Chloropyridin-2-yl)amino]-2-oxoacetic acid ethyl ester monohydrochloride

Status of research and development

Edoxaban tosylate monohy—drate is a small molecular oral anticoagulant developed by Japan No.1 Sankong Co., Ltd. It was approved in April 2011, listed in Japan in July 2011 and included in the catalogue of essential medicines. There is no project declaration of Edoxaban in our country. Europe and the United States and other countries and regions are not listed.

Market Overview

Edoxaban is the first oral anticoagulant on the market in Japan, and it is also the first time in the world. This product can inhibit thrombosis through selective, reversible and direct inhibition of FXa. Its good tolerance, oral absorption and anticoagulant activity have been verified by clinical development. Clinical trials in Japan and Taiwan have confirmed the effectiveness and safety of this product in inhibiting VTE in patients undergoing lower limb plastic surgery. With the aging of the population and the increase in the incidence of cardiovascular disease, the demand for anticoagulants is increasing. 

FXa direct inhibitors are the development trend of anticoagulants, many of which have been approved to be marketed abroad. It is believed that these drugs will benefit more patients. The global market capacity of FXa inhibitors will grow from about US $6 billion in 2008 to more than US $9 billion in 2014.Idoxaban is a direct FXa inhibitor, and FXa is the main target for the development of a new generation of anticoagulants; oral administration provides convenience for clinical use; clinical trials have proved that the product is safe and effective. Therefore, this product will have more advantages in the field of anticoagulants and get more commercial opportunities.