Five-membered heteroaromatic ring fused-pyrimidine derivatives: Design,synthesis, and hedgehog signaling pathway inhibition study |
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| Affiliation: | 1. The College of Biotechnology and Pharmaceutical Engineering, Nanjing University of Technology, No. 30 Puzhu Road, Nanjing 211800, PR China;2. Jiangsu Simcere Pharmaceutical Co. Ltd, Jiangsu Key Laboratory of Molecular Targeted Antitumor Drug Research, No. 699-18, Xuan Wu District, Nanjing 210042, PR China;3. Department of Medicinal Chemistry, School of Pharmacy, Health Science Center, Xi’an Jiaotong University, No. 76, Yanta West Road, Xi’an 710061, PR China;1. Bioscreening Unit, Department of Pharmaceutical Chemistry and Pharmacognosy, Faculty of Pharmaceutical Sciences and Center of Excellence for Innovation in Chemistry, Naresuan University, Phitsanulok 65000, Thailand;2. Department of Pharmaceutical Chemistry and Pharmacognosy, Faculty of Pharmaceutical Sciences and Center of Excellence for Innovation in Chemistry, Naresuan University, Phitsanulok 65000, Thailand;3. Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences and Center of Excellence for Innovation in Chemistry, Naresuan University, Phitsanulok 65000, Thailand;4. Department of Chemistry, Faculty of Science, Naresuan University, Phitsanulok 65000, Thailand;1. Departamento de Farmacología, Laboratorio de Farmacoquímica, Facultad de Farmacia, Universidad de Valencia, 46100 Burjassot, Valencia, Spain;2. Departamento de Química Orgánica, Facultad de Ciencias, Universidad de Málaga, 29071 Málaga, Spain;3. Départament des Sciences Expérimentales, Institut de Recherches Servier, 92150 Suresnes, France;4. UMR CNRS 8076, LERMIT, Université Paris-Sud, Laboratoire de Pharmacognosie, UFR de Pharmacie, Châtenay-Malabry F-92296, France;5. Centro de Ecología Química Agrícola-Instituto Agroforestal Mediterraneo, UPV, Campus de Vera, Edificio 6C, 46022 Valencia, Spain;1. Institute of Bioorganic Chemistry and Petrochemistry, Kyiv-94 02660, Ukraine;2. Department of Molecular and Cellular Biochemistry, College of Medicine, University of Kentucky, Lexington, KY 40536-0509, USA;3. Center for Pharmaceutical Research and Innovation, College of Pharmacy, University of Kentucky, Lexington, KY 40536-0596, USA;4. Lucille Parker Markey Cancer Center, University of Kentucky, Lexington, KY 40536-0093, USA;1. Syncom B.V., Kadijk 3, Groningen 9747 AT, The Netherlands;2. Laboratory for Endothelial Biomedicine & Vascular Drug Targeting Research, University Medical Center Groningen, University of Groningen, Hanzeplein 1, Groningen 9713 GZ, The Netherlands |
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| Abstract: | A series of novel five-membered heteroaromatic ring fused-pyrimidine derivatives including purines, pyrrolo[2,3-d]pyrimidines, pyrrolo[3,2-d]pyrimidines, thieno[2,3-d]pyrimidines, thieno[3,2-d]pyrimidines and furo[3,2-d]pyrimidines have been identified to be potent inhibitors of hedgehog signaling pathway. The synthesis and SAR of these compounds are described. Among this new series of hedgehog signaling pathway inhibitors, most compounds exhibited significant inhibitory activity compared to vismodegib, indicating that the five-membered heteroaromatic ring fused-pyrimidines stand out as encouraging scaffolds among the currently reported structural skeletons for hedgehog signaling pathway inhibitors, deserving more exploration and further investigation. |
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| Keywords: | Hedgehog signaling pathway Inhibitors Five-membered heteroaromatic ring fused-pyrimidine Synthesis |
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