6-(2-hydroxy-ethyl)-2,3-dihydro-pyrido[3,2-b][1,4]oxazine-4-carboxylic acid tert-butyl ester | 445490-28-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 6-(2-hydroxy-ethyl)-2,3-dihydro-pyrido[3,2-b][1,4]oxazine-4-carboxylic acid tert-butyl ester
• 英文别名: 6-(2-hydroxyethyl)-2,3-dihydropyrido[3,2-b][1,4]oxazine-4-carboxylic acid tert-butyl ester；tert-butyl 6-(2-hydroxyethyl)-2,3-dihydropyrido[3,2-b][1,4]oxazine-4-carboxylate
• CAS: 445490-28-8
• 化学式: C₁₄H₂₀N₂O₄
• 分子量: 280.324
• InChiKey: WSKVZCMVVPXHJR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  71.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-(2-hydroxy-ethyl)-2,3-dihydro-pyrido[3,2-b][1,4]oxazine-4-carboxylic acid tert-butyl ester 在 四氢吡咯 、 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 6-[2-(1H-Indol-5-yloxy)-ethyl]-2,3-dihydro-pyrido[3,2-b][1,4]oxazine-4-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Non-peptidic αvβ3 antagonists containing indol-1-yl propionic acids

  摘要：

  We describe the synthesis and structure/activity relationship of RGD mimetics that are potent inhibitors of the integrin alpha(v)beta(3)- Indol-1-yl propionic acids containing a variety of basic moieties at the 5-position, as well as substitutions alpha and beta to the carboxy terminus were synthesized and evaluated. Novel compounds with improved potency have been identified. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.01.028
• 作为产物：
  描述：

  6-甲基-2H-吡啶并[3,2-b]-1,4-噁嗪-3(4h)-酮 在 lithium aluminium tetrahydride 、 锂硼氢 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 反应 6.0h， 生成 6-(2-hydroxy-ethyl)-2,3-dihydro-pyrido[3,2-b][1,4]oxazine-4-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Non-peptidic αvβ3 antagonists containing indol-1-yl propionic acids

  摘要：

  We describe the synthesis and structure/activity relationship of RGD mimetics that are potent inhibitors of the integrin alpha(v)beta(3)- Indol-1-yl propionic acids containing a variety of basic moieties at the 5-position, as well as substitutions alpha and beta to the carboxy terminus were synthesized and evaluated. Novel compounds with improved potency have been identified. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.01.028

文献信息

• Substituted indoles and their use as integrin antagonists
  申请人：3-Dimensional Pharmaceuticals, Inc.

  公开号：US20020169200A1

  公开（公告）日：2002-11-14

  The present invention relates to novel substituted indole compounds that are antagonists of alpha V (&agr;v) integrins, for example &agr; v &bgr; 3 and &agr; v &bgr; 5 integrins, their pharmaceutically acceptable salts, and pharmaceutical compositions thereof. The compounds may be used in the treatment of pathological conditions mediated by &agr; v &bgr; 3 and &agr; v &bgr; 5 integrins, including such conditions as tumor growth, metastasis, restenosis, osteoporosis, inflammation, macular degeneration, diabetic retinopathy, and rheumatoid arthritis. The compounds have the general formula: 1 where R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , D, X, W, a, m, n, i, j, k and v are defined herein.

  本发明涉及新型取代吲哚化合物，其为αV（αv）整合素的拮抗剂，例如αvβ3和αvβ5整合素，其药学上可接受的盐以及其药物组合物。这些化合物可用于治疗由αvβ3和αvβ5整合素介导的病理性状况，包括肿瘤生长、转移、再狭窄、骨质疏松、炎症、黄斑变性、糖尿病视网膜病变和类风湿性关节炎等病症。这些化合物具有以下一般式： 1 其中R1、R2、R3、R4、R5、R6、R7、R8、R9、R10、R11、R12、R13、R14、D、X、W、a、m、n、i、j、k和v在此处定义。
• [EN] INDAZOLE DERIVATIVES AS αV INTEGRIN ANTAGONISTS<br/>[FR] DÉRIVÉS D'INDAZOLE EN TANT QU'ANTAGONISTES DE L'INTÉGRINE αV
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2018089357A1

  公开（公告）日：2018-05-17

  The present invention provides compounds of Formula (Ia) or (Ib): or stereoisomers, tautomers, or pharmaceutically acceptable salts or solvates thereof, wherein all the variables are as defined herein. These compounds are antagonists to αV- containing integrins. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating a disease, disorder, or condition associated with dysregulation of αV-containing integrins, such as pathological fibrosis, transplant rejection, cancer, osteoporosis, and inflammatory disorders, by using the compounds and pharmaceutical compositions.

  本发明提供了式（Ia）或（Ib）的化合物：或其立体异构体、互变异构体或药学上可接受的盐或溶剂，其中所有变量如本文所定义。这些化合物是αV-含有整合素的拮抗剂。本发明还涉及包括这些化合物的药物组合物以及使用这些化合物和药物组合物治疗与αV-含有整合素失调相关的疾病、紊乱或状况的方法，如病理性纤维化、移植排斥、癌症、骨质疏松症和炎症性疾病。
• L-alanine derivatives as a5beta1 antagonists
  申请人：Arnould Jean-Claude

  公开号：US20080182842A1

  公开（公告）日：2008-07-31

  The present invention relates to compounds that inhibit of a5b1 function, processes for their preparation, pharmaceutical compositions containing them as the active ingredient, to their use as medicaments and to their use in the manufacture of medicaments for use in the treatment in warm-blooded animals such as humans of diseases that have a significant angiogenesis or vascular component such as for treatment of solid tumours. The present invention also relates to compounds that inhibit a5b1, and also that exhibit appropriate selectivity profile(s) against other integrins.

  本发明涉及抑制a5b1功能的化合物、其制备方法、含有其作为活性成分的制药组合物、作为药物的用途以及用于制造药物以治疗温血动物（如人类）中具有显著血管生成或血管成分的疾病，例如用于实体肿瘤的治疗。本发明还涉及抑制a5b1的化合物，以及具有适当选择性谱对其他整合素的化合物。
• Substituted Indoles and Their Use as Integrin Antagonists
  申请人：Lu Tianbo

  公开号：US20070219233A1

  公开（公告）日：2007-09-20

  The present invention relates to novel substituted indole compounds that are antagonists of alpha V (αv) integrins, for example α v β 3 and α v β 5 integrins, their pharmaceutically acceptable salts, and pharmaceutical compositions thereof. The compounds may be used in the treatment of pathological conditions mediated by α v β 3 and α v β 5 integrins, including such conditions as tumor growth, metastasis, restenosis, osteoporosis, inflammation, macular degeneration, diabetic retinopathy, and rheumatoid arthritis. The compounds have the general formula: where R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , D, X, W, a, m, n, i, j, k and v are defined herein.

  本发明涉及一种新型的取代吲哚化合物，它们是αV（αv）整合素的拮抗剂，例如αvβ3和αvβ5整合素，它们的药学上可接受的盐和制药组合物。这些化合物可用于治疗由αvβ3和αvβ5整合素介导的病理状况，包括肿瘤生长、转移、再狭窄、骨质疏松、炎症、黄斑变性、糖尿病视网膜病变和类风湿性关节炎等疾病。该化合物具有以下通式：其中R1、R2、R3、R4、R5、R6、R7、R8、R9、R10、R11、R12、R13、R14、D、X、W、a、m、n、i、j、k和v在此定义。
• PHENYLALANINE DERIVATIVES
  申请人：Arnould Jean-Claude

  公开号：US20080045521A1

  公开（公告）日：2008-02-21

  The present invention relates to compounds that inhibit of a5b1 function, processes for their preparation, pharmaceutical compositions containing them as the active ingredient, to their use as medicaments and to their use in the manufacture of medicaments for use in the treatment in warm-blooded animals such as humans of diseases that have a significant angiogenesis or vascular component such as for treatment of solid tumours. The present invention also relates to a5b1 antagonists that also exhibit appropriate selectivity profile(s) against other integrins.

  本发明涉及抑制a5b1功能的化合物，其制备过程，含有其作为活性成分的制药组合物，以及它们作为药物在温血动物（如人类）中治疗具有明显血管生成或血管成分的疾病，例如固体肿瘤的制药用途。本发明还涉及a5b1拮抗剂，其还表现出对其他整合素的适当选择性特征。