Discovery of AZD8165 – a clinical candidate from a novel series of neutral thrombin inhibitors
| Autor: | C. Wern, Y. Örtengren, M. Strimfors, Ulf Eriksson, S. Nielsen, A.-C. Egnell, Ulf Bredberg, Joakim Bergman, T. Skjaeret, S. Pehrsson, Jonas Brånalt, K.-J. Hoffman, K. Abrahamsson, Ingemar Nilsson, Maria Ölwegård-Halvarsson, Polla Magnus, David Gustafsson, P. Andersson |
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| Rok vydání: | 2016 |
| Předmět: |
Pharmacology
chemistry.chemical_classification 010405 organic chemistry Chemistry Organic Chemistry Pharmaceutical Science Prodrug 010402 general chemistry 01 natural sciences Biochemistry 0104 chemical sciences Thrombin Docking (molecular) Drug Discovery medicine Propionate Molecular Medicine Clinical evaluation medicine.drug Discovery and development of direct thrombin inhibitors |
| Zdroj: | MedChemComm. 7:272-281 |
| ISSN: | 2040-2511 2040-2503 |
| Popis: | A novel series of neutral thrombin inhibitors has been developed using a selection process based on docking experiments and property calculations and predictions. This work resulted in the identification of the highly potent thrombin inhibitor compound 85 (Ki = 300 pM) and the corresponding propionate prodrug 5 (AZD8165) as a candidate for clinical evaluation in the treatment of thrombosis and related diseases. AZD8165 was found to be safe and well tolerated and delivered the expected pharmacological response in a phase I trial in healthy male volunteers. |
| Databáze: | OpenAIRE |
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