Click approach to the discovery of 1,2,3-triazolylsalicylamides as potent Aurora kinase inhibitors |
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| Institution: | 1. College of Pharmacy & Graduate School of Pharmaceutical Sciences, Global Top 5 Research Program, Ewha Womans University, 11-1 Daehyun-Dong, Seodaemun-Gu, Seoul 120-750, Republic of Korea;2. Department of Pharmacy, College of Pharmacy, Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, Kyeonggi-do 426-791, Republic of Korea;1. Discovery Chemistry Research, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, United States;2. Department of Chemistry, University of Wisconsin, Madison, WI 53706, United States;1. Université de Nantes, Nantes Atlantique Universités, Laboratoire de Chimie Thérapeutique, Cibles et Médicaments des Infections et du Cancer IICiMed EA 1155, UFR des Sciences Pharmaceutiques et Biologiques, 1 rue Gaston Veil, 44035 Nantes, France;2. Æterna Zentaris GmbH, Weismuellerstrasse 50, 60314 Frankfurt/Main, Germany;1. Department of Pharmacy, College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, Kyeonggi-do 426-791, Republic of Korea;2. College of Pharmacy & Graduate School of Pharmaceutical Sciences, Global Top 5 Research Program, Ewha Womans University, 11-1 Daehyun-Dong, Seodaemun-Gu, Seoul 120-750, Republic of Korea;1. ZJU-ENS Joint Laboratory of Medicinal Chemistry, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China;2. National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China;1. School of Pharmacy and Center for Innovative Therapeutics Discovery, National Taiwan University, No. 33, Lin Sen South Road, Taipei 10050, Taiwan;2. Biomedical Engineering Research Laboratories, Industrial Technology Research Institute, No. 321, Section 2, Guangfu Road, Hsinchu 30011, Taiwan;3. Department of Applied Chemistry, Providence University, No. 200, Section 7, Taiwan Boulevard, Taichung 43301, Taiwan;4. Department of Life Science, College of Life Science, National Taiwan University, No. 1, Section 4, Roosevelt Road, Taipei 10617, Taiwan;1. State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China;2. School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China;3. School of Engineering, China Pharmaceutical University, Nanjing 210009, China;4. Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China |
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| Abstract: | A series of 1,2,3-triazolylsalicylamide derivatives has been developed from the antiproliferative agent 7 and was evaluated for their Aurora kinase inhibitory activity. The novel 1,2,3-triazolylsalicylamide scaffold could be readily assembled by Cu(I)-catalyzed azide–alkyne 1,3-dipolar cycloaddition, allowing rapid access to the structurally diverse analogues. The synthesized 1,2,3-triazolylsalicylamide derivatives revealed a significant Aurora kinase inhibitory activity. In particular, 8g inhibited Aurora A with IC50 values of 0.37 μM. The critical role of phenolic –OH in the binding was confirmed by a molecular modeling study. |
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| Keywords: | Aurora kinase Click chemistry Library 1 2 3-Triazole Anticancer |
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