Pyrrolopyrimidine-inhibitors with hydantoin moiety as spacer can explore P4/S4 interaction on plasmin |
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| Affiliation: | 1. Hiroshima International University, Faculty of Pharmaceutical Sciences, 5-1-1, Hirokoshingai, Kure, Hiroshima 737-0112, Japan;2. Computer-Aided Molecular Modeling Research Center, Kansai (CAMM-Kansai), 5-1-7, Ohmichidori, Nagata-ku, Kobe 653-0833, Japan;3. Kobe Research Projects on Thrombosis and Haemostasis, 3-15-18, Asahigaoka, Tarumi-ku, Kobe 655-0033, Japan;4. Kobe Gakuin University, Faculty of Pharmaceutical Sciences, 1-1-3, Minatojima, Chuo-ku, Kobe 650-8586, Japan;1. Department of Pharmaceutical Sciences, University of Maryland, School of Pharmacy, 20 N. Pine Street, Baltimore, MD 21201, USA;2. Department of Basic Pharmaceutical Sciences, West Virginia University, PO Box 9500, Morgantown, WV 26506, USA;1. Department of ECE, National Institute of Technology Rourkela, 769008, India;2. School of Electrical Science, Indian Institute of Technology, Bhubaneswar 751013, India;3. IDCOM, The University of Edinburgh, Edinburgh, UK;4. Department of CS & IT, G. G. Vishwavidyalaya, Central University, Bilaspur 495009, India;1. Department of Mathematics and Computer, Shangrao Normal University, Shangrao 334001, China;2. Institute of Physics, Chinese Academy of Sciences, Beijing 100190, China;3. Department of Pure Mathematics, University of Waterloo, Waterloo, Ontario, Canada;4. Institute for Quantum Computing, University of Waterloo, Waterloo, Ontario, Canada;5. Center for Quantum Technologies, National University of Singapore, Singapore;6. Institute of Physics, Chinese Academy of Sciences, Beijing 100190, China |
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| Abstract: | In the development of plasmin inhibitors, a novel chemotype, pyrrolopyrimidine scaffold possessing two motifs, a hydantoin-containing P4 moiety and a warhead-containing P1 moiety, is uncovered. A unique feature of the new line of the plasmin inhibitors is that the interaction between the plasmin inhibitors and key subsites in plasmin can be controlled by a spacer like hydantoin. The application of the novel chemotype is demonstrated by 1n and provides further evidence on the importance of hydantoin as the spacer. |
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| Keywords: | Plasmin inhibitors P4 moiety Scaffold Pyrrolopyrimidine Hydantoin Structure–activity relationship |
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