Synthesis and structureactivity relationships of novel. Qsars are mathematical models used to predict measures of toxicity from the physical characteristics of the structure of chemicals known as molecular descriptors. Apixaban is an oral anticoagulant and direct inhibitor of factor xa which is used to decrease the risk of venous thromboses, systemic embolization and stroke in patients with atrial fibrillation, and lower the risk of deep vein thrombosis and pulmonary embolus after knee or hip replacement surgery. Apixaban bms56224701 is a direct factor xa inhibitor with an ic50 of 0.
Design, synthesis, and structureactivity relationship of novel and. Toxicity estimation software tool test safer chemicals. Compounds 14a, 16, 18c, 26c, 35a, and 35b were further examined for their inhibition activity against human fxa in vitro and rat venous thrombosis in vivo. Intensive structure activity relationship sar and structure pharmacokinetic relationship spr studies on this new series led to the discovery of compound 11a. The discovery and development of rivaroxaban, an oral. A common structural feature that is present with compound 4 and its predecessor.
Synthesis and structureactivity relationship of potent, selective and orally active anthranilamidebased factor xa inhibitors. Eliquis apixaban tablets may treat, side effects, dosage, drug interactions, warnings. Apixaban lets say you have an 80 year old grandmother who has an arthritic knee. The toxicity estimation software tool test was developed to allow users to easily estimate the toxicity of chemicals using quantitative structure activity relationships qsars methodologies. The inhibitor was built with the program quanta accelrys. Structureactivity relationship studies for multitarget antithrombotic. Youll learn what it is better known as, its general and specific drug class, and a bit about its structure. As such it is the concept of linking chemical structure to a chemical property e. M and 99% inhibition rate, was identified for further evaluation as an fxa inhibitor. The first of these compounds is apixaban, which was approved in.
Find information about common, infrequent and rare side effects of apixaban oral. I would not have made it through the program without all of your support and. Application of weakly basic sulfoximine group as novel s4 binding. The antifxa activity consistently exhibited a close linear relationship with apixaban.
Evolution of phenylethanolamine class of drugs as agonist, their pharmacology and therapeutic action. Sar tools like cdd vault can detect correlations and build models used to evaluate new chemical structures to predict their biological activity. Synthesis and structureactivity relationships of novel direct thrombin inhibitors based on pentapeptide fm 19 by elizabeth andrea girnys a dissertation submitted in partial fulfillment of the requirements for the degree of doctor of philosophy medicinal chemistry in the university of michigan 2012 doctoral committee. Rivaroxaban structure and structureactivity relationship studies for.
Discovery and development of direct xa inhibitors wikipedia. Importantly, compound 40 apixaban, bms562247 is a significant. Apixaban is an oral, direct factor xa inhibitor that inhibits both free and clotbound factor xa, and. To occupy the p2 cavity on a larger scale and enhance the hydrogen bonding to glu146, a series of nitrogenous heterocyclic were introduced into pyrazole c3 to replace the carboxamido moiety.
The most promising compound 14a, with an ic50 fxa value of 0. Synthesis and structureactivity relationships of novel direct thrombin inhibitors based on. Over the last 60 years there have been a multitude of ways to capture structureactivity relationships. Eliquis apixaban is indicated to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. Simplifying qsar and molecular modeling study by dr. The body eliminates apixaban through the gastrointestinal systems, by way of feces and bile, through urine, and some of it is lost through the metabolic process in the liver. Four drugs from the class of direct xa inhibitors are marketed worldwide. Structure activity relationship sar is an approach designed to find relationships between chemical structure or structuralrelated properties and biological activity or target property of studied compounds.
Medchem express hy50667 factor xa medchem express hy50667 factor xa targetmol t1736. Pdf structureactivity relationship studies for multitarget. There is a relationship between molecular structures and their biological activity, and this principle is referred to as structure activity relationship sar. This article presents the history of rivaroxabans development, from the structure activity relationship studies that led to its discovery to the preclinical and clinical studies, and also. Prophylaxis of dvt following hip or knee replacement. On the g6g directory of omics and intelligent software, i searched for qsar analysis, and received two product abstracts. Design, synthesis, and structureactivity relationship of. We can broadly divide them into two groups those based on statistical or data mining methods e. During the sar development of apixaban there were three groups that needed to be tested to attain maximum potency and bioavailability. Design, synthesis, and structureactivity and structure. According to the structure activity relationships sars, the 1,4,5,6tetrahydro7 h pyrazolo3,4 c pyridin7one scaffold p3 moiety was retained.
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