ABSTRACT
Anticoagulants serve as the primary strategy for the prevention and treatment of both arterial and venous thromboembolism. Anticoagulants disrupt coagulation by interfering at various points in the coagulation cascade. This class of medications does not lyse clots that already exist; rather, it prevents thrombus formation and prevents or slows the extension of an existing clot. For decades, the standard therapy for patients requiring oral anticoagulation was warfarin. However, due to some of the shortcomings of warfarin, including the need for continuous routine monitoring, longtime onset and offset of anticoagulation effect, major food and drug interactions, and high incidence of bleeding, newer agents, termed direct oral anticoagulants, or DOACs were developed. This article will provide a review of clinically important information regarding the most commonly used anticoagulants and their reversal agents.
Subject(s)
Anticoagulants/standards , Anticoagulants/classification , Benzamides/classification , Benzamides/standards , Dabigatran/classification , Dabigatran/standards , Humans , Pyrazoles/classification , Pyrazoles/standards , Pyridines/classification , Pyridines/standards , Pyridones/classification , Pyridones/standards , Rivaroxaban/classification , Rivaroxaban/standards , Thiazoles/classification , Thiazoles/standards , Venous Thromboembolism/drug therapy , Venous Thromboembolism/prevention & control , Warfarin/classification , Warfarin/standardsABSTRACT
Warfarin has been the established oral anticoagulant for the last 50 years, being effective in the prevention and treatment of venous and arterial thromboembolic disorders. However, the frequent requirement for INR monitoring, multiple drug and food interactions have fuelled the need for development of new oral anticoagulants. Dabigatran is the first of a series of new oral anticoagulants that are emerging as the successors to warfarin. This new group of anticoagulants is rapidly gaining FDA and NICE approval and has proven non-inferiority to warfarin and viable alternatives to warfarin in the coming years. Given the obvious impact of this on dental treatment in the primary care and hospital setting this article aims to increase familiarisation with this new medicine group.
Subject(s)
Anticoagulants/classification , Anticoagulants/therapeutic use , Antithrombin Proteins/classification , Antithrombin Proteins/therapeutic use , Benzimidazoles/classification , Benzimidazoles/therapeutic use , Dabigatran , Factor Xa Inhibitors , Humans , Morpholines/classification , Morpholines/therapeutic use , Prodrugs/classification , Prodrugs/therapeutic use , Pyrazoles/classification , Pyrazoles/therapeutic use , Pyridines/classification , Pyridines/therapeutic use , Pyridones/classification , Pyridones/therapeutic use , Rivaroxaban , Thiophenes/classification , Thiophenes/therapeutic use , Thromboembolism/prevention & control , Warfarin/therapeutic useABSTRACT
The synthesis and the preliminary expansion of this new class of CDK2 inhibitors are presented. The synthesis was accomplished using a solution-phase protocol amenable to rapid parallel expansion and suitable to be scaled-up in view of possible lead development. Following a medicinal chemistry program aimed at improving cell permeability and selectivity, a series of compounds with nanomolar activity in the biochemical assay and able to efficiently inhibit tumor cell proliferation has been obtained.
Subject(s)
CDC2-CDC28 Kinases/antagonists & inhibitors , Enzyme Inhibitors/classification , Enzyme Inhibitors/pharmacology , Pyrazoles/classification , Pyrazoles/pharmacology , Cell Line, Tumor , Cell Proliferation/drug effects , Crystallization , Crystallography, X-Ray , Cyclin A/antagonists & inhibitors , Cyclin-Dependent Kinase 2 , Enzyme Inhibitors/chemical synthesis , Glycogen Synthase Kinase 3/antagonists & inhibitors , Humans , Models, Molecular , Molecular Structure , Pyrazoles/chemical synthesis , Structure-Activity RelationshipABSTRACT
High-throughput screening identified the 3,4-diarylpyrazole CCT018159 as a novel and potent (7.1 microM) inhibitor of Hsp90 ATPase activity. Here, we describe the synthesis of CCT018159 and a number of close analogues together with data on their biochemical properties. Some initial structure-activity relationships are discussed, as well as the crystal structure of CCT018159 bound to Hsp90.