Academic Journal
Discovery of 5-Phenylpyrazolopyrimidinone Analogs as Potent Antitrypanosomal Agents with In Vivo Efficacy
| العنوان: | Discovery of 5-Phenylpyrazolopyrimidinone Analogs as Potent Antitrypanosomal Agents with In Vivo Efficacy |
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| المؤلفون: | Zheng, Yang, van den Kerkhof, Magali, van der Meer, Tiffany, Gul, Sheraz, Kuzikov, Maria, Ellinger, Bernhard, de Esch, Iwan J.P., Siderius, Marco, Matheeussen, An, Maes, Louis, Sterk, Geert Jan, Caljon, Guy, Leurs, Rob |
| المصدر: | Zheng , Y , van den Kerkhof , M , van der Meer , T , Gul , S , Kuzikov , M , Ellinger , B , de Esch , I J P , Siderius , M , Matheeussen , A , Maes , L , Sterk , G J , Caljon , G & Leurs , R 2023 , ' Discovery of 5-Phenylpyrazolopyrimidinone Analogs as Potent Antitrypanosomal Agents with In Vivo Efficacy ' , Journal of medicinal chemistry , vol. 66 , no. 15 , pp. 10252–10264 . https://doi.org/10.1021/acs.jmedchem.3c00161 |
| سنة النشر: | 2023 |
| الوصف: | Human African Trypanosomiasis (HAT), caused by Trypanosoma brucei, is one of the neglected tropical diseases with a continuing need for new medication. We here describe the discovery of 5-phenylpyrazolopyrimidinone analogs as a novel series of phenotypic antitrypanosomal agents. The most potent compound, 30 (NPD-2975), has an in vitro IC 50 of 70 nM against T. b. brucei with no apparent toxicity against human MRC-5 lung fibroblasts. Showing good physicochemical properties, low toxicity potential, acceptable metabolic stability, and other pharmacokinetic features, 30 was further evaluated in an acute mouse model of T. b. brucei infection. After oral dosing at 50 mg/kg twice per day for five consecutive days, all infected mice were cured. Given its good drug-like properties and high in vivo antitrypanosomal potential, the 5-phenylpyrazolopyrimidinone analog 30 represents a promising lead for future drug development to treat HAT. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1021/acs.jmedchem.3c00161 |
| الاتاحة: | https://research.vu.nl/en/publications/2a60ef90-35f6-488c-82ca-cc6d99e82799 https://doi.org/10.1021/acs.jmedchem.3c00161 https://hdl.handle.net/1871.1/2a60ef90-35f6-488c-82ca-cc6d99e82799 http://www.scopus.com/inward/record.url?scp=85166428037&partnerID=8YFLogxK http://www.scopus.com/inward/citedby.url?scp=85166428037&partnerID=8YFLogxK |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.F8DAEC5 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1021/acs.jmedchem.3c00161 |
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