タイトル | Discovery of Potent and Orally Bioavailable Pyridine N-Oxide-Based Factor XIa Inhibitors through Exploiting Nonclassical Interactions. |
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ジャーナル・号・ページ | J. Med. Chem., Vol. 65, Page 10419-10440, Year 2022 |
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掲載日 | 2022年5月11日 (構造データの登録日) |
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著者 | Xu, G. / Liu, Z. / Wang, X. / Lu, T. / DesJarlais, R.L. / Thieu, T. / Zhang, J. / Devine, Z.H. / Du, F. / Li, Q. ...Xu, G. / Liu, Z. / Wang, X. / Lu, T. / DesJarlais, R.L. / Thieu, T. / Zhang, J. / Devine, Z.H. / Du, F. / Li, Q. / Milligan, C.M. / Shaffer, P. / Cedervall, P.E. / Spurlino, J.C. / Stratton, C.F. / Pietrak, B. / Szewczuk, L.M. / Wong, V. / Steele, R.A. / Bruinzeel, W. / Chintala, M. / Silva, J. / Gaul, M.D. / Macielag, M.J. / Nargund, R. |
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リンク | J. Med. Chem. / PubMed:35862732 |
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手法 | X線回折 |
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解像度 | 1.472 - 1.8 Å |
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構造データ | PDB-7v0z: Factor XIa in Complex with Compound 2a 手法: X-RAY DIFFRACTION / 解像度: 1.8 Å PDB-7v10: Factor XIa in Complex with Compound 2d 手法: X-RAY DIFFRACTION / 解像度: 1.798 Å PDB-7v11: Factor XIa in Complex with Compound 2e 手法: X-RAY DIFFRACTION / 解像度: 1.472 Å PDB-7v12: Factor XIa in Complex with Compound 2f 手法: X-RAY DIFFRACTION / 解像度: 1.631 Å PDB-7v13: Factor XIa in Complex with Compound 2g 手法: X-RAY DIFFRACTION / 解像度: 1.589 Å PDB-7v14: Factor XIa in Complex with Compound 2h 手法: X-RAY DIFFRACTION / 解像度: 1.697 Å PDB-7v15: Factor XIa in Complex with Compound 2i 手法: X-RAY DIFFRACTION / 解像度: 1.679 Å PDB-7v16: Factor XIa in Complex with Compound 2j 手法: X-RAY DIFFRACTION / 解像度: 1.505 Å PDB-7v17: Factor XIa in Complex with Compound 2k 手法: X-RAY DIFFRACTION / 解像度: 1.522 Å PDB-7v18: Factor XIa in Complex with Compound 3f 手法: X-RAY DIFFRACTION / 解像度: 1.732 Å |
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化合物 | ChemComp-OQ6: methyl ~{N}-[4-[1-[(1~{R})-1-[5-[5-chloranyl-2-(1,2,3,4-tetrazol-1-yl)phenyl]-1-oxidanyl-pyridin-2-yl]-2-cyclopropyl-ethyl]pyrazol-4-yl]phenyl]carbamate
ChemComp-OQI: methyl ~{N}-[4-[1-[(1~{R})-1-[5-[3-chloranyl-2-fluoranyl-6-(1,2,3,4-tetrazol-1-yl)phenyl]-1-oxidanyl-pyridin-2-yl]-2-cyclopropyl-ethyl]pyrazol-4-yl]phenyl]carbamate
ChemComp-OQO: 5-[1-[(1~{R})-1-[5-[3-chloranyl-2-fluoranyl-6-(1,2,3,4-tetrazol-1-yl)phenyl]-1-oxidanyl-pyridin-2-yl]-2-cyclopropyl-ethyl]pyrazol-4-yl]-6-methyl-pyridin-2-amine
ChemComp-OR0: 5-[1-[(1~{R})-1-[5-[3-chloranyl-2-fluoranyl-6-(1,2,3,4-tetrazol-1-yl)phenyl]-1-oxidanyl-pyridin-2-yl]-2-cyclopropyl-ethyl]pyrazol-4-yl]-6-fluoranyl-pyridin-2-amine
ChemComp-ORF: 3-chloranyl-4-[1-[(1~{R})-1-[5-[3-chloranyl-2-fluoranyl-6-(1,2,3,4-tetrazol-1-yl)phenyl]-1-oxidanyl-pyridin-2-yl]-2-cyclopropyl-ethyl]pyrazol-4-yl]-5-fluoranyl-pyridine
ChemComp-ORU: 5-[1-[(1~{R})-1-[5-[3-chloranyl-2-fluoranyl-6-(1,2,3,4-tetrazol-1-yl)phenyl]-1-oxidanyl-pyridin-2-yl]-2-cyclopropyl-ethyl]pyrazol-4-yl]-1,3-thiazole
ChemComp-OSX: 5-[1-[(1~{R})-1-[5-[3-chloranyl-2-fluoranyl-6-(1,2,3,4-tetrazol-1-yl)phenyl]-1-oxidanyl-pyridin-2-yl]-2-cyclopropyl-ethyl]pyrazol-4-yl]-4-methyl-1,3-thiazole
ChemComp-OT7: 5-[3-chloranyl-2-fluoranyl-6-(1,2,3,4-tetrazol-1-yl)phenyl]-2-[(1~{R})-2-cyclopropyl-1-[4-(2-methylpyrazol-3-yl)pyrazol-1-yl]ethyl]-1-oxidanyl-pyridine
ChemComp-OTL: 5-[3-chloranyl-2-fluoranyl-6-(1,2,3,4-tetrazol-1-yl)phenyl]-2-[(1~{R})-2-cyclopropyl-1-[4-(3-methylimidazol-4-yl)pyrazol-1-yl]ethyl]-1-oxidanyl-pyridine
ChemComp-OTX: 2-[(1~{R})-3-[bis(fluoranyl)methoxy]-1-[4-(3-methyl-1,2,3-triazol-4-yl)pyrazol-1-yl]propyl]-5-[3-chloranyl-6-(4-chloranyl-1,2,3-triazol-1-yl)-2-fluoranyl-phenyl]-1-oxidanyl-pyridine
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由来 | - homo sapiens (ヒト)
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キーワード | Blood Clotting / Hydrolase / SERINE PROTEASE / COAGULATION FACTOR |
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