1-(N-hydroxycarbamimidoyl)-octahydro-isoindole-2-carboxylic acid tert-butyl ester | 783326-06-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 1-(N-hydroxycarbamimidoyl)-octahydro-isoindole-2-carboxylic acid tert-butyl ester
• 英文别名: tert-butyl 1-[(Z)-N'-hydroxycarbamimidoyl]-1,3,3a,4,5,6,7,7a-octahydroisoindole-2-carboxylate
• CAS: 783326-06-7
• 化学式: C₁₄H₂₅N₃O₃
• 分子量: 283.371
• InChiKey: HTOIWBGMOUPORA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  88.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(N-hydroxycarbamimidoyl)-octahydro-isoindole-2-carboxylic acid tert-butyl ester 、 Carbonyldiimidazole 在 二氯甲烷 、 sodium hydroxide 、 乙酸乙酯 、 Sodium sulfate-III 作用下， 以 四氢呋喃 为溶剂， 反应 3.5h， 以to afford the title compound (1.1 g, 76%) as a colorless oil的产率得到1-(5-oxo-4,5-dihydro-[1,2,4]oxadiazol-3-yl)-octahydro-isoindole-2-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  [C]-fused bicyclic proline derivatives and their use for treating arthritic conditions

  摘要：

  本发明涉及一种[c]-融合的双环脯氨酸衍生物化合物或其药学上可接受的盐；一种包括该化合物或其盐的制药组合物，以及治疗疾病的方法，包括但不限于预防或抑制关节软骨损伤和预防或治疗以关节软骨损伤、关节炎或关节疼痛为特征的疾病的方法。[c]-融合的双环脯氨酸衍生物是如上所述的化合物I。以关节软骨损伤或关节疼痛为特征的疾病包括骨关节炎和类风湿性关节炎等。类风湿性关节炎还表现为关节炎。本发明还涉及合成和制备[c]-融合的双环脯氨酸衍生物或其药学上可接受的盐的方法。

  公开号：

  US20050137215A1
• 作为产物：
  描述：

  1-cyano-octahydro-isoindole-2-carboxylic acid tert-butyl ester 在 盐酸羟胺 作用下， 以 乙醇 、 水 为溶剂， 反应 18.0h， 以88%的产率得到1-(N-hydroxycarbamimidoyl)-octahydro-isoindole-2-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  [EN] [C]-FUSED BICYCLIC PROLINE DERIVATIVES AND THEIR USE FOR TREATING ARTHRITIC CONDITIONS
  [FR] DERIVES DE PROLINE BICYCLIQUES 20041028US2003008861A1LIN LINUS S [US], et al20030109example 10, step C example 11, step A example 29, step c (starting material)X2,8XBERGMEIER S C ET AL: "Synthesis of Bicyclic Proline Analogs Using a Formal [3 + 2] Intramolecular Aziridine-Allylsilane Cycloaddition Reaction", TETRAHEDRON, ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM, NL, vol. 55, no. 26, 25 June 1999 (1999-06-25), pages 8025 - 8038, XP004168571, ISSN: 0040-4020BERGMEIER S C ET ALSynthesis of Bicyclic Proline Analogs Using a Formal [3 + 2] Intramolecular Aziridine-Allylsilane Cycloaddition ReactionTETRAHEDRON, ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM, NL1999062555260040-40208025803845Scheme 7X2XDATABASE BEILSTEIN BEILSTEIN INSTITUTE FOR ORGANIC CHEMISTRY, FRANKFURT-MAIN, DE; XP002288925, Database accession no. BRN:388906BEILSTEINBEILSTEIN INSTITUTE FOR ORGANIC CHEMISTRY, FRANKFURT-MAIN, DEBRN:388906AX4XMURAYAMA ET AL, YAKUGAKU ZASSHI, vol. 85, 1965, pages 765 - 769MURAYAMA ET ALYAKUGAKU ZASSHI196585765769WO0027808A1AVENTIS PHARMA GMBH [DE]20000518214814211517A1-9AWO03074048A1WARNER LAMBERT CO [US], et al2003091235253626PX1-9PXOTHMAN M ET AL: "New Fused Lactones from Indolizinediones via N-Acyliminium Ions", TETRAHEDRON, ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM, NL, vol. 54, no. 30, 23 July 1998 (1998-07-23), pages 8737 - 8744, XP004124041, ISSN: 0040-4020OTHMAN M ET ALNew Fused Lactones from Indolizinediones via N-Acyliminium IonsTETRAHEDRON, ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM, NL1998072354300040-4020873787443A-EScheme 1X1XGUILLERM G ET AL: "Synthesis of Hydroxylated Pyrrolidines Derivatives as Potential Inhibitors of SAH/MTA Nucleosidase", TETRAHEDRON LETTERS, vol. 28, no. 5, 1987, pages 535 - 538, XP002288924GUILLERM G ET ALSynthesis of Hydroxylated Pyrrolidines Derivatives as Potential Inhibitors of SAH/MTA NucleosidaseTETRAHEDRON LETTERS19872855355384AScheme 2X1X

  摘要：

  本发明涉及一种[c]-融合的双环脯氨酸衍生物，或其药用可接受的盐；包括该化合物或其盐的药物组合物；以及治疗疾病的方法，包括但不限于预防或抑制关节软骨损伤，以及预防或治疗以关节软骨损伤、关节炎或关节疼痛为特征的疾病的方法。[c]-融合的双环脯氨酸衍生物是如上所述的I式化合物。以关节软骨损伤或关节疼痛为特征的疾病包括，例如，骨关节炎和类风湿性关节炎。类风湿性关节炎还以关节炎为特征。本发明还涉及合成和制备[c]-融合的双环脯氨酸衍生物或其药用可接受的盐的方法。

  公开号：

  WO2004092134A1

文献信息

• EP1615886A1
  申请人：——

  公开号：EP1615886A1

  公开（公告）日：2006-01-18
• [EN] [C]-FUSED BICYCLIC PROLINE DERIVATIVES AND THEIR USE FOR TREATING ARTHRITIC CONDITIONS<br/>[FR] DERIVES DE PROLINE BICYCLIQUES 20041028US2003008861A1LIN LINUS S [US], et al20030109example 10, step C example 11, step A example 29, step c (starting material)X2,8XBERGMEIER S C ET AL: "Synthesis of Bicyclic Proline Analogs Using a Formal [3 + 2] Intramolecular Aziridine-Allylsilane Cycloaddition Reaction", TETRAHEDRON, ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM, NL, vol. 55, no. 26, 25 June 1999 (1999-06-25), pages 8025 - 8038, XP004168571, ISSN: 0040-4020BERGMEIER S C ET ALSynthesis of Bicyclic Proline Analogs Using a Formal [3 + 2] Intramolecular Aziridine-Allylsilane Cycloaddition ReactionTETRAHEDRON, ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM, NL1999062555260040-40208025803845Scheme 7X2XDATABASE BEILSTEIN BEILSTEIN INSTITUTE FOR ORGANIC CHEMISTRY, FRANKFURT-MAIN, DE; XP002288925, Database accession no. BRN:388906BEILSTEINBEILSTEIN INSTITUTE FOR ORGANIC CHEMISTRY, FRANKFURT-MAIN, DEBRN:388906AX4XMURAYAMA ET AL, YAKUGAKU ZASSHI, vol. 85, 1965, pages 765 - 769MURAYAMA ET ALYAKUGAKU ZASSHI196585765769WO0027808A1AVENTIS PHARMA GMBH [DE]20000518214814211517A1-9AWO03074048A1WARNER LAMBERT CO [US], et al2003091235253626PX1-9PXOTHMAN M ET AL: "New Fused Lactones from Indolizinediones via N-Acyliminium Ions", TETRAHEDRON, ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM, NL, vol. 54, no. 30, 23 July 1998 (1998-07-23), pages 8737 - 8744, XP004124041, ISSN: 0040-4020OTHMAN M ET ALNew Fused Lactones from Indolizinediones via N-Acyliminium IonsTETRAHEDRON, ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM, NL1998072354300040-4020873787443A-EScheme 1X1XGUILLERM G ET AL: "Synthesis of Hydroxylated Pyrrolidines Derivatives as Potential Inhibitors of SAH/MTA Nucleosidase", TETRAHEDRON LETTERS, vol. 28, no. 5, 1987, pages 535 - 538, XP002288924GUILLERM G ET ALSynthesis of Hydroxylated Pyrrolidines Derivatives as Potential Inhibitors of SAH/MTA NucleosidaseTETRAHEDRON LETTERS19872855355384AScheme 2X1X
  申请人：WARNER LAMBERT CO

  公开号：WO2004092134A1

  公开（公告）日：2004-10-28

  This invention relates to a compound which is [c]-fused bicyclic proline derivative, or a pharmaceutically acceptable salt thereof; a pharmaceutical composition comprising the compound or the salt thereof, and methods of treating diseases, including, but not limited to, methods of preventing or inhibiting joint cartilage damage and preventing or treating diseases characterized by joint cartilage damage, joint inflammation, or joint pain. The [c]-fused bicyclic proline derivatives are compounds of Formula I as described above. Diseases characterized by joint cartilage damage or joint pain include, for example, osteoarthritis and rheumatoid arthritis. Rheumatoid arthritis is also characterized by joint inflammation. This invention also relates to methods of synthesizing and preparing the [c]-fused bicyclic proline derivatives, or a pharmaceutically acceptable salt thereof.

  本发明涉及一种[c]-融合的双环脯氨酸衍生物，或其药用可接受的盐；包括该化合物或其盐的药物组合物；以及治疗疾病的方法，包括但不限于预防或抑制关节软骨损伤，以及预防或治疗以关节软骨损伤、关节炎或关节疼痛为特征的疾病的方法。[c]-融合的双环脯氨酸衍生物是如上所述的I式化合物。以关节软骨损伤或关节疼痛为特征的疾病包括，例如，骨关节炎和类风湿性关节炎。类风湿性关节炎还以关节炎为特征。本发明还涉及合成和制备[c]-融合的双环脯氨酸衍生物或其药用可接受的盐的方法。
• [C]-fused bicyclic proline derivatives and their use for treating arthritic conditions
  申请人：Guzzo R. Peter

  公开号：US20050137215A1

  公开（公告）日：2005-06-23

  This invention relates to a compound which is [c]-fused bicyclic proline derivative, or a pharmaceutically acceptable salt thereof; a pharmaceutical composition comprising the compound or the salt thereof, and methods of treating diseases, including, but not limited to, methods of preventing or inhibiting joint cartilage damage and preventing or treating diseases characterized by joint cartilage damage, joint inflammation, or joint pain. The [c]-fused bicyclic proline derivatives are compounds of Formula I as described above. Diseases characterized by joint cartilage damage or joint pain include, for example, osteoarthritis and rheumatoid arthritis. Rheumatoid arthritis is also characterized by joint inflammation. This invention also relates to methods of synthesizing and preparing the [c]-fused bicyclic proline derivatives, or a pharmaceutically acceptable salt thereof.

  本发明涉及一种[c]-融合的双环脯氨酸衍生物化合物或其药学上可接受的盐；一种包括该化合物或其盐的制药组合物，以及治疗疾病的方法，包括但不限于预防或抑制关节软骨损伤和预防或治疗以关节软骨损伤、关节炎或关节疼痛为特征的疾病的方法。[c]-融合的双环脯氨酸衍生物是如上所述的化合物I。以关节软骨损伤或关节疼痛为特征的疾病包括骨关节炎和类风湿性关节炎等。类风湿性关节炎还表现为关节炎。本发明还涉及合成和制备[c]-融合的双环脯氨酸衍生物或其药学上可接受的盐的方法。