PMID- 25981610
OWN - NLM
STAT- MEDLINE
DCOM- 20160803
LR  - 20190911
IS  - 1873-5592 (Electronic)
IS  - 1389-4501 (Linking)
VI  - 16
IP  - 11
DP  - 2015
TI  - Advances in Inhibitors of FXa.
PG  - 1207-32
AB  - Thromboembolic diseases such as deep vein thrombosis (DVT), pulmonary embolism 
      (PE), myocardial infarction (MI) and ischemic strokes are mainly responsible for 
      people's morbidity and mortality and have severely affected the people's quality 
      of life all over the world. According to WHO statistics, an average of 17 million 
      people are killed by the thromboembolic diseases each year globally. Therefore, 
      the prevention and treatment of thromboembolic diseases have received widespread 
      attention in recent years. Based on thrombotic mechanism, anti-thrombotic drugs 
      are mainly divided into anticoagulants, antiplatelet agents and direct 
      thrombolytic drugs. In particular, anticoagulants such as vitamin K antagonists 
      (VKAs), unfractionated heparin (UFH), and low-molecular-weight heparins (LMWHs) 
      have become the main therapies for pre-treatment of thromboembolic disorders. 
      However, the limitations of traditional anticoagulants such as slow onset of 
      action, dose-adjusted requirement, drug-drug and drug-food interactions have 
      restricted their improvement in the clinical treatment. The mechanism of the 
      thromboembolic disorders has indicated that coagulation factor Xa (fXa) plays a 
      pivotal role in the blood coagulation cascade. Thus, selective inhibition of fXa 
      by diminishing the amplified generation of thrombin without affecting the 
      pre-existing thrombin levels can provide better antithrombotic effect, thereby 
      causing less impairment of primary hemostasis. In this paper, we mainly introduce 
      the recent advances of fXa inhibitors, with focus on their biological activity 
      and structure-activity relationship (SAR) information. In particular, the 
      inspirations from the structures of the fXa inhibitors and their future direction 
      are highlighted.
FAU - Guo, Liwei
AU  - Guo L
FAU - Ma, Shutao
AU  - Ma S
AD  - Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong 
      University, 44 West Culture Road, Jinan 250012, P. R. China. mashutao@sdu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - United Arab Emirates
TA  - Curr Drug Targets
JT  - Current drug targets
JID - 100960531
RN  - 0 (Benzene Derivatives)
RN  - 0 (Coumarins)
RN  - 0 (Factor Xa Inhibitors)
RN  - 0 (Heterocyclic Compounds)
RN  - 0 (Piperidines)
RN  - 0 (Pyrrolidines)
SB  - IM
MH  - Animals
MH  - Benzene Derivatives/pharmacology/therapeutic use
MH  - Blood Coagulation/drug effects/physiology
MH  - Blood Coagulation Disorders/drug therapy
MH  - Chemistry
MH  - Coumarins/pharmacology/therapeutic use
MH  - Factor Xa Inhibitors/pharmacology/*therapeutic use
MH  - Heterocyclic Compounds/pharmacology/therapeutic use
MH  - Humans
MH  - Piperidines/pharmacology/therapeutic use
MH  - Pyrrolidines/pharmacology/therapeutic use
MH  - Structure-Activity Relationship
EDAT- 2015/05/20 06:00
MHDA- 2016/08/04 06:00
CRDT- 2015/05/19 06:00
PHST- 2014/10/13 00:00 [received]
PHST- 2015/03/02 00:00 [revised]
PHST- 2015/05/04 00:00 [accepted]
PHST- 2015/05/19 06:00 [entrez]
PHST- 2015/05/20 06:00 [pubmed]
PHST- 2016/08/04 06:00 [medline]
AID - CDT-EPUB-67385 [pii]
AID - 10.2174/1389450116666150518095533 [doi]
PST - ppublish
SO  - Curr Drug Targets. 2015;16(11):1207-32. doi: 10.2174/1389450116666150518095533.