With the objective to prepare novel non-peptidic thrombin inhibitors, bioisosteres of the inhibitory tripeptide D-Phe-Pro-Arg chain have been examined. Thus, the P1 Arg was replaced with p-amidinobenzylamine, an elongated homologue of the same and with 2,5-dichloro benzylamine. The P2-P3, D-Phe-Pro, was replaced with a novel tartaric acid template coupled to a series of readily available, mainly lipophilic, amines. Some of these compounds exhibit promising thrombin inhibition activity in vitro, IC(50 ) approximately 5.9 microM.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/s0968-0896(01)00426-6 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
High-power short-duration setting prevents changes of periprocedural thrombotic markers and the onset of silent stroke in patients with atrial fibrillation.
Heart Rhythm O2
December 2024
Division of Cardiovascular Medicine, Department of Medicine, Jichi Medical University School of Medicine, Shimotsuke, Japan.
Background: It remains unclear whether the newly adopted high-power, short-duration (HP-SD) setting in ablation for atrial fibrillation (AF) impacts periprocedural thrombotic markers or silent stroke (SS) onset.
Objective: The aim of the present study was to investigate the clinical impact of HP-SD setting ablation on changes in periprocedural thrombotic markers and the onset of SS.
Methods: We enrolled 101 AF patients: the HP-SD group (n = 67) using 50 W and the conventional ablation group (n = 34) using 30 to 40 W.
Chemotherapy alters thrombomodulin and factor VIIIc expression resulting in acquired activated protein C resistance and enhanced thrombin generation in cancer associated thrombosis.
Thromb Res
December 2024
Department of Obstetrics and Gynaecology, Trinity College Dublin, Dublin, Ireland; Trinity St. James's Cancer Institute, Dublin, Ireland. Electronic address:
Background: Tumour type, treatment and patient related factors contribute to cancer associated venous thromboembolism (VTE), however, the role of each factor and the mechanisms involved are not understood.
Aim: To assess the role of the tumour, and of chemotherapy, in mediating the procoagulant response associated with VTE in gynaecological cancer patients.
Methods: Gynaecological cancer patients who developed VTE during follow-up (n = 59) (VTE+) were matched with treatment naïve(treatment (-)(VTE-)(n = 120) and chemotherapy treated patients(treatment (+)(VTE-) (n = 57)).
Real-Time Imaging of Platelet-Initiated Plasma Clot Formation and Lysis Unveils Distinct Impacts of Anticoagulants.
Thromb Haemost
January 2025
Department of Medical Physiology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Background: Fibrinolysis is spatiotemporally well-regulated and greatly influenced by activated platelets and coagulation activity. Our previous real-time imaging analyses revealed that clotting commences on activated platelet surfaces, resulting in uneven-density fibrin structures, and that fibrinolysis initiates in dense fibrin regions and extends to the periphery. Despite the widespread clinical use of direct oral anticoagulants (DOACs), their impact on thrombin-dependent activation of thrombin-activatable fibrinolysis inhibitor (TAFI) and fibrinolysis remains unclear.
View Article and Find Full Text PDFReplacement of a single residue changes the primary specificity of thrombin.
Fertil Steril
January 2025
Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis, MO 63104 USA. Electronic address:
Background: Thrombin prefers substrates carrying Arg at the site of cleavage (P1) because of the presence of D189 in the primary specificity (S1) pocket but can also cleave substrates carrying Phe at P1. The structural basis of this property is unknown.
Objective: Solve the X-ray structure of thrombin bound to a ligand carrying Phe at P1 and investigate the effects of replacing D189.
Steroids and Malignancy Increase Local Heparanase and Decrease Markers of Osteoblast Activity in Bone Tissue Microcirculation.
Biomolecules
November 2024
Thrombosis and Hemostasis Unit, Rambam Health Care Campus, Haifa 3109601, Israel.
Bone metastasis and steroids are known to activate the coagulation system and induce osteoporosis, pathological bone fractures, and bone pain. Heparanase is a protein known to enhance the hemostatic system and to promote angiogenesis, metastasis, and inflammation. The objective of the present study was to evaluate the effects of steroids and malignancy on the coagulation factors and osteoblast activity in the bone tissue.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!