{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1390282679409559936.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.5551/jat.3293"}},{"identifier":{"@type":"NAID","@value":"130004444446"}},{"identifier":{"@type":"URI","@value":"https://search.jamas.or.jp/link/ui/2011149013"}}],"dc:title":[{"@language":"en","@value":"Antiplatelet activity and structure-activity relationship study of Pyrazolopyridine Derivatives as potential series for treating thrombotic diseases"}],"dc:language":"en","description":[{"type":"abstract","notation":[{"@language":"en","@value":"Aim: Platelets plays a central role in hemostatic processes and consequently are similarly involved in pathological processes, such as arterial thrombosis and atherosclerosis. Herein we described the synthesis, antiplatelet profile and structure-activity relationship (SAR) of a new series of <i>N'</i>-substitutedphenylmethylene-1<i>H</i>-pyrazolo[3,4-<i>b</i>]pyridine-carbohydrazide derivatives (3a-3k).<BR> Methods: These compounds were synthesized in good yield and tested in platelet aggregation assays using collagen, ADP and arachidonic acid as agonists. We also performed a SAR studies using SPARTAN' 08 program, <i>in silico</i> ADMET screening and the Lipinski “ rule of five ” using Osiris Property Explorer and molinspiration on-line programs.<BR>Results: Interestingly, the new compounds were active against collagen and arachidonic acid (AA) with the two most actives compounds (3a and 3c - IC<sub>50</sub>=61 μM and 68 μM respectively) almost 5-fold more potent than aspirin (IC<sub>50</sub>=300 μM). These derivatives showed low theoretical toxicity risks in <i>in silico</i> ADMET screening and fulfilled the Lipinski rule of five, suggesting good oral biodisponibility.<BR>Conclusion: This work showed carbohydrazide group as potential for designing new antiplatelets. On that purpose, 3a and 3c may act as prototypes to generate more efficient and safe molecules for treating thrombotic diseases."}],"abstractLicenseFlag":"disallow"}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1410282679409559810","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000257809800"}],"foaf:name":[{"@language":"en","@value":"Geraldo RB"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Laboratório de Antibióticos, Bioquímica e Modelagem Molecular (LABioMol)-Instituto de Biologia, Universidade Federal Fluminense, Niterói."}]},{"@id":"https://cir.nii.ac.jp/crid/1410282679409559941","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000257809805"}],"foaf:name":[{"@language":"en","@value":"Bello ML"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Laboratório de Química Medicinal (LQMed)-Faculdade de Farmácia, Universidade Federal Fluminense, Niterói."}]},{"@id":"https://cir.nii.ac.jp/crid/1410282679409559943","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000257809809"}],"foaf:name":[{"@language":"en","@value":"Abreu PA"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Laboratório de Antibióticos, Bioquímica e Modelagem Molecular (LABioMol)-Instituto de Biologia, Universidade Federal Fluminense, Niterói."}]},{"@id":"https://cir.nii.ac.jp/crid/1410282679409559942","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000257809808"}],"foaf:name":[{"@language":"en","@value":"Nagashima T"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Laboratório de Antibióticos, Bioquímica e Modelagem Molecular (LABioMol)-Instituto de Biologia, Universidade Federal Fluminense, Niterói."}]},{"@id":"https://cir.nii.ac.jp/crid/1410282679409559938","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000257809807"}],"foaf:name":[{"@language":"en","@value":"Vera MAF"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Laboratório de Química Medicinal (LQMed)-Faculdade de Farmácia, Universidade Federal Fluminense, Niterói."}]},{"@id":"https://cir.nii.ac.jp/crid/1410282679409559809","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000257809801"}],"foaf:name":[{"@language":"en","@value":"Freitas ACC"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Laboratório de Química Medicinal (LQMed)-Faculdade de Farmácia, Universidade Federal Fluminense, Niterói."}]},{"@id":"https://cir.nii.ac.jp/crid/1410282679409559945","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000257809806"}],"foaf:name":[{"@language":"en","@value":"Dias LRS"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Laboratório de Química Medicinal (LQMed)-Faculdade de Farmácia, Universidade Federal Fluminense, Niterói."}]},{"@id":"https://cir.nii.ac.jp/crid/1410282679409559939","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000257809812"}],"foaf:name":[{"@language":"en","@value":"Cabral LM"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Laboratório de Modelagem Molecular e QSAR (ModMolQSAR)-Faculdade de Farmácia, Universidade Federal do Rio de Janeiro."}]},{"@id":"https://cir.nii.ac.jp/crid/1410282679409559937","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000257809802"}],"foaf:name":[{"@language":"en","@value":"Kalil MV"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Laboratório de Antibióticos, Bioquímica e Modelagem Molecular (LABioMol)-Instituto de Biologia, Universidade Federal Fluminense, Niterói."}]},{"@id":"https://cir.nii.ac.jp/crid/1410282679409559936","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000257809810"}],"foaf:name":[{"@language":"en","@value":"Santos MB"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Laboratório de Química Medicinal (LQMed)-Faculdade de Farmácia, Universidade Federal Fluminense, Niterói."}]},{"@id":"https://cir.nii.ac.jp/crid/1410282679409559940","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000257809803"}],"foaf:name":[{"@language":"en","@value":"Rodrigues CR"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Laboratório de Modelagem Molecular e QSAR (ModMolQSAR)-Faculdade de Farmácia, Universidade Federal do Rio de Janeiro."}]},{"@id":"https://cir.nii.ac.jp/crid/1410282679409559808","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000257809811"}],"foaf:name":[{"@language":"en","@value":"Albuquerque MG"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Laboratório de Modelagem Molecular e QSAR (ModMolQSAR)-Faculdade de Farmácia, Universidade Federal do Rio de Janeiro."}]},{"@id":"https://cir.nii.ac.jp/crid/1410282679409559944","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000257809804"}],"foaf:name":[{"@language":"en","@value":"Castro HC"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Laboratório de Antibióticos, Bioquímica e Modelagem Molecular (LABioMol)-Instituto de Biologia, Universidade Federal Fluminense, Niterói."}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"13403478"},{"@type":"EISSN","@value":"18803873"}],"prism:publicationName":[{"@language":"en","@value":"Journal of Atherosclerosis and Thrombosis"},{"@language":"ja","@value":"Ｊｏｕｒｎａｌ　ｏｆ　Ａｔｈｅｒｏｓｃｌｅｒｏｓｉｓ　ａｎｄ　Ｔｈｒｏｍｂｏｓｉｓ"},{"@language":"en","@value":"JAT"},{"@language":"en","@value":"J Atheroscler Thromb"},{"@language":"ja","@value":"Ｊ　Ａｔｈｅｒｏｓｃｌｅｒ　Ｔｈｒｏｍｂ"}],"dc:publisher":[{"@language":"en","@value":"Japan Atherosclerosis Society"},{"@language":"ja","@value":"一般社団法人 日本動脈硬化学会"}],"prism:publicationDate":"2010","prism:volume":"17","prism:number":"7","prism:startingPage":"730","prism:endingPage":"739"},"reviewed":"false","url":[{"@id":"https://search.jamas.or.jp/link/ui/2011149013"}],"availableAt":"2010","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=Antiplatelets","dc:title":"Antiplatelets"},{"@id":"https://cir.nii.ac.jp/all?q=Stroke","dc:title":"Stroke"},{"@id":"https://cir.nii.ac.jp/all?q=Structure-activity%20relationship(SAR)","dc:title":"Structure-activity relationship(SAR)"}],"relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360011143579240320","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Synthesis and anti-platelet activity of novel arylsulfonate–acylhydrazone derivatives, designed as antithrombotic candidates"}]},{"@id":"https://cir.nii.ac.jp/crid/1360574095308630528","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Antiplatelet resistance with aspirin and clopidogrel: Is it real and does it matter?"}]},{"@id":"https://cir.nii.ac.jp/crid/1360574096265370112","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Platelet–collagen interactions: membrane receptors and intracellular signalling pathways"}]},{"@id":"https://cir.nii.ac.jp/crid/1361137043413205888","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"RM1: A reparameterization of AM1 for H, C, N, O, P, S, F, Cl, Br, and I"}]},{"@id":"https://cir.nii.ac.jp/crid/1361137044720537472","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings 1PII of original article: S0169-409X(96)00423-1. The article was originally published in Advanced Drug Delivery Reviews 23 (1997) 3–25. 1"}]},{"@id":"https://cir.nii.ac.jp/crid/1361137045178319872","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Chapter 10 Thromboxane Synthetase Inhibitors and Antagonists"}]},{"@id":"https://cir.nii.ac.jp/crid/1361418518994242688","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Identification of a Potential Lead Structure for Designing New Antimicrobials to Treat Infections Caused by Staphylococcus epidermidis-Resistant Strains"}]},{"@id":"https://cir.nii.ac.jp/crid/1361418520326837504","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Synthesis, in vitro evaluation, and SAR studies of a potential antichagasic 1H-pyrazolo[3,4-b]pyridine series"}]},{"@id":"https://cir.nii.ac.jp/crid/1361699994734385664","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Clinical overview of promising nonthienopyridine antiplatelet agents"}]},{"@id":"https://cir.nii.ac.jp/crid/1361981470458426880","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"PROSTAGLANDIN ENDOPEROXIDES, THROMBOXANE A<sub>2</sub> AND ADENOSINE DIPHOSPHATE IN COLLAGEN‐INDUCED AGGREGATION OF RABBIT PLATELETS"}]},{"@id":"https://cir.nii.ac.jp/crid/1362262943582855936","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Clinical implications of aspirin resistance"}]},{"@id":"https://cir.nii.ac.jp/crid/1362262945282344704","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Prasugrel"}]},{"@id":"https://cir.nii.ac.jp/crid/1362544419886294272","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Synthesis, antichagasic in vitro evaluation, cytotoxicity assays, molecular modeling and SAR/QSAR studies of a 2-phenyl-3-(1-phenyl-1H-pyrazol-4-yl)-acrylic acid benzylidene-carbohydrazide series"}]},{"@id":"https://cir.nii.ac.jp/crid/1362544421308890496","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Computing chemistry on the web"}]},{"@id":"https://cir.nii.ac.jp/crid/1362825894641334400","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Stroke and atherothrombosis: An Update on the Role of Antiplatelet Therapy"}]},{"@id":"https://cir.nii.ac.jp/crid/1363107371192554624","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Role of Cellular Elements in Thrombus Formation and Dissolution"}]},{"@id":"https://cir.nii.ac.jp/crid/1363388843831389952","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Antiplatelet drugs in cardiological practice: Established strategies and new developments"}]},{"@id":"https://cir.nii.ac.jp/crid/1363388844946240640","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"SAR of a series of anti-HSV-1 acridone derivatives, and a rational acridone-based design of a new anti-HSV-1 3H-benzo[b]pyrazolo[3,4-h]-1,6-naphthyridine series"}]},{"@id":"https://cir.nii.ac.jp/crid/1363388845052491008","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Thromboxane A2: Physiology/pathophysiology, cellular signal transduction and pharmacology"}]},{"@id":"https://cir.nii.ac.jp/crid/1363951794110863360","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Platelet physiology and thrombosis"}]},{"@id":"https://cir.nii.ac.jp/crid/1364233269760757504","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Cell Adhesion Mechanisms in Platelets"}]},{"@id":"https://cir.nii.ac.jp/crid/1364233270444495232","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Oral anticoagulants versus antiplatelet therapy for preventing further vascular events after transient ischaemic attack or minor stroke of presumed arterial origin"}]}],"dataSourceIdentifier":[{"@type":"JALC","@value":"oai:japanlinkcenter.org:0035417899"},{"@type":"CROSSREF","@value":"10.5551/jat.3293"},{"@type":"CIA","@value":"130004444446"}]}