Discovery of the Novel Antithrombotic Agent 5-Chloro-<i>N</i>-({(5<i>S</i>)-2-oxo-3- [4-(3-oxomorpholin-4-yl)phenyl]-1,3-oxazolidin-5-yl}methyl)thiophene- 2-carboxamide (BAY 59-7939):  An Oral, Direct Factor Xa Inhibitor

Roehrig, Susanne; Straub, Alexander; Pohlmann, Jens; Lampe, Thomas; Pernerstorfer, Josef; Schlemmer, Karl‐Heinz; Reinemer, Peter; Perzborn, Elisabeth

doi:10.1021/jm050101d

Cited by 411 publications

(304 citation statements)

References 22 publications

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“…15 Because factor Xa represents the junction of the intrinsic and extrinsic pathways of the blood-coagulation cascade, its inhibition prevents the generation of the final common coagulation enzyme catalyst, thrombin ( Figure 1). Rivaroxaban exhibits no inhibitory effects on thrombin (activated factor II) and has no direct effects on platelet function.…”

Section: Rivaroxabanmentioning

confidence: 99%

Emergency Management of Bleeding Associated With Old and New Oral Anticoagulants

Peacock

Gearhart

Mills

2012

Clinical Cardiology

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As major prescribers of oral anticoagulants, cardiologists must be familiar with strategies to manage bleeding, the principal complication associated with all anticoagulants, and to reverse anticoagulant effects in acute‐care settings. The purpose of this manuscript is to review currently available information regarding dabigatran and rivaroxaban, the 2 novel oral anticoagulants approved to date in the United States. Further, we suggest reasonable interventions for the clinician faced with a patient who suffers a major bleeding event while receiving one of these agents. Data sources were peer‐reviewed publications, US Food and Drug Administration documents in the public domain, and approved US prescribing information for dabigatran (Pradaxa) and rivaroxaban (Xarelto). Strategies for management of bleeding and reversal of anticoagulant effects from warfarin include vitamin K, fresh frozen plasma, and prothrombin complex concentrates. For rivaroxaban and dabigatran, appropriate therapies include support and observation, which are likely to be effective for the majority of patients because of the short half‐lives of these agents. In severe life‐threatening hemorrhage, clotting‐factor substitutes may be appropriate in certain situations. Validated protocols specific to each agent remain to be developed. Clin. Cardiol. 2012 doi: 10.1002/clc.22037Editorial support for this paper was provided by Janssen Scientific Affairs, LLC. W.F.P. has received research grants (>$10 000) from Abbott, Alere, Baxter, Brahms, Novartis, and The Medicines Company. He has been a consultant (<$10 000) for Abbott, Alere, Eli Lilly, and The Medicines Company; served on the speaker's bureau (<$10 000) for Abbott and Alere; and has ownership interest (<$10 000) in Comprehensive Research Associates LLC, Vital Sensors, and Emergencies in Medicine LLC. M.M.G and R.M.M. are full‐time employees of Janssen Scientific Affairs, LLC. The authors have no other funding, financial relationships, or conflicts of interest to disclose.

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Section: Rivaroxabanmentioning

confidence: 99%

Emergency Management of Bleeding Associated With Old and New Oral Anticoagulants

Peacock

Gearhart

Mills

2012

Clinical Cardiology

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“…It is an oxazolidinone derivative anticoagulant that inhibits both free Factor Xa and Factor Xa bound in the prothrombinase complex [3]. It is a highly selective direct Factor Xa inhibitor with oral bioavailability and rapid onset of action.…”

Section: Rivis5-chloro-n-({(5s)mentioning

confidence: 99%

High Performance Liquid Chromatography, TLC Densitometry, Firstderivative and First-derivative ratio spectrophotometry for de-termination of Rivaroxaban and its alkaline Degradates in Bulk Powder and its Tablets

Ib¹,

Aa²,

Ma³

2013

J Chromat Separation Techniq

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Four sensitive and selective stability indicating methods for the determination of rivaroxaban (RIV) were developed. Method a was an isocratic RP-HPLC, good resolution between peaks corresponding to the degradates from analyte was achieved on C18 column. The mobile phase is 1.2% w/v potassium dihydrogen phosphate pH 3.5 ± 0.2 and acetonitrile (70:30, v/v). The detection was carried out at 280 nm. Method B depends on quantitative densitometric determination of thin layer chromatography TLC of rivaroxaban in the presence of it's degradates without any interference. The developing system was chloroform-isobutyl alcohol (50:50 v/v).The chromatogram was scanned at 280 nm. Method C was based on the first derivative (D 1 ) measurement of the drug at 237.4 nm; zero contribution point of its alkaline degradates. Method D was based on the resolution of the drug and its alkaline degradates by first derivative ratio spectra (DD 1 successfully applied for the determination of rivaroxaban in bulk powder, pharmaceutical formulation and in presence of its alkaline degradates. The obtained results were statistically analyzed and compared with those obtained by the reported method.

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“…O anticoagulante rivaroxaban (Xarelto ® , Bayer), que atua através da inibição do fator Xa, 32 e o inibidor não peptídico da protease do vírus da imunodeficiência humana (HIV -human immunodeficiency virus) tipranavir (Aptivus ® , Pfizer/ Boehringer Ingelheim) 33 são medicamentos desenvolvidos a partir de hits identificados por HTS.…”

Section: Triagem Biológica Automatizada Em Alta Escalaunclassified

Integração das técnicas de triagem virtual e triagem biológica automatizada em alta escala: oportunidades e desafios em P&D de fármacos

Ferreira¹,

Oliva²,

Andricopulo³

2011

Quím. Nova

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Recebido em 16/1/11; aceito em 2/6/11; publicado na web em 26/7/11 INTEGRATING VIRTUAL AND HIGH-THROUGHPUT SCREENING: OPPORTUNITIES AND CHALLENGES IN DRUG RESEARCH AND DEVELOPMENT. High-throughput screening (HTS) and virtual screening (VS) are useful methods employed in drug discovery, allowing the identification of promising hits for lead optimization. The efficiency of these approaches depends on a number of factors, such as the organization of high quality databases of compounds and the parameterization of essential components of the screen process. This brief review presents the basic principles of the HTS and VS methods, as well as a perspective of the utility and integration of these drug design approaches, highlighting current opportunities and future challenges in medicinal chemistry.Keywords: high-throughput screening; virtual screening; drug design. INTRODUÇÃOA descoberta de novos fármacos é um grande desafio para a indústria farmacêutica moderna. Os altos investimentos na área de pesquisa e desenvolvimento (P&D) contrastam com o número de novos medicamentos que têm chegado ao mercado nos últimos anos. 1 Este complexo panorama tem forçado a adoção de novas estratégias com o objetivo de aumentar a eficiência do processo de P&D, tendo como alicerces as inovações científicas, tecnológicas e empresariais.Considerando-se o expressivo número de alvos biológicos (proteínas alvo) promissores para o planejamento de fármacos, as técnicas de triagem biológica automatizada em alta escala (HTS -high throughput screening) e de triagem virtual (VS -virtual screening) têm ocupado papel de destaque entre as estratégias modernas exploradas na identificação de novas substâncias bioativas. Desde o seu surgimento, a HTS tem sido amplamente utilizada pela indústria farmacêutica, propiciando a avaliação de milhões de compostos contra proteínas alvo. Embora esta estratégia tenha despertado a esperança de uma revolução na descoberta de substâncias bioativas, em pouco tempo as suas limitações ficaram evidentes. 2 A ocorrência de um número elevado de falso-positivos, identificados inicialmente como hits (termo em inglês para designar um novo ligante ou composto bioativo) nos ensaios bioquímicos em alta escala pode ser destacada como um dos grandes problemas. 3 Os múltiplos modos de interação ou mecanismos de ação apresentados pelos diferentes hits selecionados podem também ser mencionados como outros importantes obstácu-los. 4 Além disso, o número possível de compostos com propriedades fármaco-similar (drug-like) 5 é várias ordens de magnitude maior do que o número de compostos que pode ser analisado nos processos de HTS. Portanto, o planejamento das bases de dados de compostos é essencial, sendo que fatores como propriedades moleculares e físico-químicas, ou ainda a diversidade química, devem ser considerados. [6][7][8] Com os notáveis avanços da biologia estrutural e a disponibilidade de recursos computacionais de alto desempenho, a VS surgiu como importante alternativa à HTS. A VS é um método in silico ("computacional") empre...

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Discovery of the Novel Antithrombotic Agent 5-Chloro-N-({(5S)-2-oxo-3- [4-(3-oxomorpholin-4-yl)phenyl]-1,3-oxazolidin-5-yl}methyl)thiophene- 2-carboxamide (BAY 59-7939): An Oral, Direct Factor Xa Inhibitor

Cited by 411 publications

References 22 publications

Emergency Management of Bleeding Associated With Old and New Oral Anticoagulants

Emergency Management of Bleeding Associated With Old and New Oral Anticoagulants

High Performance Liquid Chromatography, TLC Densitometry, Firstderivative and First-derivative ratio spectrophotometry for de-termination of Rivaroxaban and its alkaline Degradates in Bulk Powder and its Tablets

Integração das técnicas de triagem virtual e triagem biológica automatizada em alta escala: oportunidades e desafios em P&D de fármacos

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