A new generation of orally active antithrombotics: Comparing strategies
                        in the GPIIb/IIIa, thrombin and factor Xa areas

Adang, Anton E.P.; Rewinkel, J. B. M.

doi:10.1358/dof.2000.025.04.858662

Cited by 27 publications

(12 citation statements)

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“…Recent approaches to anticoagulant therapy have been directed toward identifying direct small molecule inhibitors of specific coagulation cascade enzymes which possess the pharmacokinetic properties required for once daily oral administration. Assuming predictable pharmacokinetics, the direct antithrombotic action of these inhibitors should render routine monitoring of coagulation levels unnecessary.…”

Section: Introductionmentioning

confidence: 99%

Metabolism-Directed Optimization of 3-Aminopyrazinone Acetamide Thrombin Inhibitors. Development of an Orally Bioavailable Series Containing P1 and P3 Pyridines

et al. 2003

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Recent efforts in the field of thrombin inhibitor research have focused on the identification of compounds with good oral bioavailability and pharmacokinetics. In this manuscript we describe a metabolism-based approach to the optimization of the 3-(2-phenethylamino)-6-methylpyrazinone acetamide template (e.g., 1) which resulted in the modification of each of the three principal components (i.e., P1, P2, P3) comprising this series. As a result of these studies, several potent thrombin inhibitors (e.g., 20, 24, 25) were identified which exhibit high levels of oral bioavailability and long plasma half-lives.

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Section: Introductionmentioning

confidence: 99%

Metabolism-Directed Optimization of 3-Aminopyrazinone Acetamide Thrombin Inhibitors. Development of an Orally Bioavailable Series Containing P1 and P3 Pyridines

et al. 2003

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“…As such, factor Xa is an attractive target for new anticoagulant agents. 8, 9 Factor Xa (51 kDa) consists of a heavy chain (251 amino acids) and a light chain (139 amino acids), held together by a single disulfide bond. The heavy chain incorporates the catalytic triad composed of His-57, Asp-102 and Ser-195.…”

Section: Introductionmentioning

confidence: 99%

“…Result of quantitative K D work and competition binding experiments with the high affinity reference ligand TPAM(9) …”

mentioning

confidence: 99%

Exploring the active site of human factor Xa protein by NMR screening of small molecule probes

Fielding¹,

Fletcher²,

Rutherford³

et al. 2003

Org. Biomol. Chem.

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A collection of small molecules (MW < 350 Da) was screened for binding to human factor Xa using saturation transfer difference NMR spectroscopy to detect binding. The NMR screening experiments identified four hits. Binding isotherms constructed from NMR linewidth data showed that the binding affinities of the hits were all in the 30-210 microM range. Competition binding experiments showed that three of the ligands were displaced by a known microM inhibitor of factor Xa. The success of the method for identifying new ligands and the relevance of this information to the design of new factor Xa inhibitors are discussed.

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“…Thrombin very efficiently initiates fibrin formation, platelet aggregation, and activation of factors V and VIII. Selective inhibitors of thrombin and factor Xa are expected to be therapeutically useful in the treatment or prophylaxis of thromboembolic diseases [71][72][73].…”

Section: Antithrombotic Activitymentioning

confidence: 99%

Pharmacological Profile of Quinoxalinone

Ramli

Moussaïf

Karrouchi³

et al. 2014

Journal of Chemistry

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Quinoxalinone and its derivatives are used in organic synthesis for building natural and designed synthetic compounds and they have been frequently utilized as suitable skeletons for the design of biologically active compound. This review covers updated information on the most active quinoxalinone derivatives that have been reported to show considerable pharmacological actions such as antimicrobial, anti-inflammatory, antidiabetic, antiviral, antitumor, and antitubercular activity. It can act as an important tool for chemists to develop newer quinoxalinone derivatives that may prove to be better agents in terms of efficacy and safety.

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A new generation of orally active antithrombotics: Comparing strategies in the GPIIb/IIIa, thrombin and factor Xa areas

Cited by 27 publications

References 0 publications

Metabolism-Directed Optimization of 3-Aminopyrazinone Acetamide Thrombin Inhibitors. Development of an Orally Bioavailable Series Containing P1 and P3 Pyridines

Metabolism-Directed Optimization of 3-Aminopyrazinone Acetamide Thrombin Inhibitors. Development of an Orally Bioavailable Series Containing P1 and P3 Pyridines

Exploring the active site of human factor Xa protein by NMR screening of small molecule probes

Pharmacological Profile of Quinoxalinone

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