Related Experiment Video
Updated: Aug 10, 2026

Rapid Point-of-Care Assay of Enoxaparin Anticoagulant Efficacy in Whole Blood
Published on: October 12, 2012
L-374,087, an efficacious, orally bioavailable, pyridinone acetamide thrombin inhibitor
P E Sanderson1, K J Cutrona, B D Dorsey
1Department of Biological Chemistry, Merck Research Laboratories, West Point, PA 19486, USA.
Abstract:
Replacement of the amidinopiperidine P1 group of 3-benzylsulfonylamino-6-methyl-2-pyridinone acetamide thrombin inhibitor L-373,890 (2) with a mildly basic 5-linked 2-amino-6-methylpyridine results in an equipotent compound L-374,087 (5, Ki = 0.5 nM). Compound 5 is highly selective for thrombin over trypsin, is efficacious in the rat ferric chloride model of arterial thrombosis and is orally bioavailable in dogs and cynomolgus monkeys. The structural basis for the critical importance of both methyl groups in 5 was confirmed by X-ray crystallography.
More Related Videos
07:13Characterizing Modulators of Protease-Activated Receptors with a Calcium Mobilization Assay Using a Plate Reader
Published on: May 24, 2024
10:29Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
Related Concept Videos
Anticoagulant Drugs: Low-Molecular-Weight Heparins
Treatment for Pulmonary Arterial Hypertension: Phosphodiesterase Inhibitors
Among the PDE5 inhibitors, sildenafil (Revatio) stands out as a competitive and selective inhibitor. It operates by elevating cellular levels of cGMP and augmenting signaling through the cGMP-PKG pathway, promoting vasodilation. Upon oral...
Treatment for Pulmonary Arterial Hypertension: Prostacyclin Receptor Agonists
These agonists bind to the IPR receptor situated on the plasma membrane of the pulmonary artery smooth muscle cells. This binding triggers a cascade of reactions known as the GS-AC-cAMP-PKA pathway. This pathway results in the relaxation of smooth muscle...
Impact of Pharmacokinetic–Pharmacodynamic Models: Regulatory Decisions
Venous Thrombosis III: Interprofessional Care
Antiviral Nucleoside Inhibitors