2-(((9H-芴-9-基)甲氧基)羰基)-8-(叔丁氧基羰基)-2,8-二氮杂螺[4.5]癸烷-3-羧酸 | 849928-23-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 中文名称: 2-(((9H-芴-9-基)甲氧基)羰基)-8-(叔丁氧基羰基)-2,8-二氮杂螺[4.5]癸烷-3-羧酸
• 中文别名: 2,8-二氮杂-螺[4.5]癸烷-2,3,8-三甲酸8-叔丁基酯2-(9H-芴-9-基甲基)酯
• 英文名称: 2,8-diazaspiro[4.5]decane-2,3,8-tricarboxylic acid 8-tert-butyl ester 2-(9H-fluoren-9-ylmethyl) ester
• 英文别名: 2-(((9H-Fluoren-9-yl)methoxy)carbonyl)-8-(tert-butoxycarbonyl)-2,8-diazaspiro[4.5]decane-3-carboxylic acid；2-(9H-fluoren-9-ylmethoxycarbonyl)-8-[(2-methylpropan-2-yl)oxycarbonyl]-2,8-diazaspiro[4.5]decane-3-carboxylic acid
• CAS: 849928-23-0
• 化学式: C₂₉H₃₄N₂O₆
• 分子量: 506.599
• InChiKey: URRGFGKYPWMHCY-UHFFFAOYSA-N

物化性质

• 沸点：
  674.2±55.0 °C(Predicted)
• 密度：
  1.31±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  37
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  96.4
• 氢给体数：
  1
• 氢受体数：
  6

安全信息

• 海关编码：
  2933990090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  2-(((9H-芴-9-基)甲氧基)羰基)-8-(叔丁氧基羰基)-2,8-二氮杂螺[4.5]癸烷-3-羧酸 、 苯胺 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 21.0h， 生成 8-tert-butyl 2-(9H-fluoren-9-ylmethyl) 3-(anilinocarbonyl)-2,8-diazaspiro[4.5]decane-2,8-dicarboxylate
  参考文献：
  名称：

  Spirocyclic compounds

  摘要：

  本发明涉及一类新型的取代螺环化合物。这些化合物可以抑制组蛋白去乙酰化酶，并适用于在选择性诱导终末分化、阻止肿瘤细胞生长和/或凋亡的过程中使用，从而抑制这些细胞的增殖。因此，本发明的化合物在治疗具有肿瘤特征的患者方面是有用的，这些肿瘤具有肿瘤细胞的增殖。本发明的化合物还可能在预防和治疗TRX介导的疾病方面有用，例如自身免疫、过敏和炎症性疾病，以及预防和/或治疗中枢神经系统（CNS）疾病，如神经退行性疾病。本发明还提供了包括本发明化合物的药物组合物和这些药物组合物的安全用药方案，这些方案易于遵循，并在体内产生这些化合物的治疗有效量。

  公开号：

  US20070117824A1

文献信息

• [EN] HETEROCYCLIC DERIVATIVES AS IAP BINDING COMPOUNDS<br/>[FR] DÉRIVÉS HÉTÉROCYCLIQUES CONVENANT COMME COMPOSÉS SE LIANT AUX INHIBITEURS DE PROTÉINES D'APOPTOSE
  申请人：NUEVOLUTION AS

  公开号：WO2009152824A1

  公开（公告）日：2009-12-23

  The present invention relates to compounds of formula (I), or pharmaceutically acceptable salts, solvates thereof, that bind to Inhibitor of Apoptosis Proteins (IAPs). The compounds of the invention may be used as diagnostic and therapeutic agents in the treatment of proliferative diseases, such as cancer, for promoting apoptosis in proliferating cells, and for sensitizing cells to inducers of apoptosis. The present invention furthermore provides a polymeric compound of formulas (VI) or (VII), comprising either at least two monomeric units of compounds of formula (I), or at least one monomeric unit of a compound of formula (I) and an entity E. The present invention further relates to pharmaceutical compositions comprising said compounds of formulas (I), (VI), and (VII) and the use of said compounds in medicine.

  本发明涉及式(I)的化合物，或其药学上可接受的盐、溶剂化合物，这些化合物与凋亡抑制蛋白(IAPs)结合。本发明的化合物可用作诊断和治疗剂，用于治疗增殖性疾病，如癌症，促进增殖细胞中的凋亡，并使细胞对凋亡诱导剂敏感。本发明还提供了具有式(VI)或(VII)的聚合物化合物，包括至少两个式(I)化合物的单体单位，或至少一个式(I)化合物的单体单位和实体E。本发明还涉及包含所述式(I)、(VI)和(VII)化合物的药物组合物以及在医学中使用所述化合物的用途。
• SPIROCYCLIC COMPOUNDS
  申请人：Mampreian Dawn M.

  公开号：US20110098268A1

  公开（公告）日：2011-04-28

  The present invention relates to a novel class of substituted spirocyclic compounds. These compounds can inhibit histone deacetylase and are suitable for use in selectively inducing terminal differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The compounds of the invention may also be useful in the prevention and treatment of TRX-mediated diseases, such as autoimmune, allergic and inflammatory diseases, and in the prevention and/or treatment of diseases of the central nervous system (CNS), such as neurodegenerative diseases. The present invention further provides pharmaceutical compositions comprising the compounds of the instant invention and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of these compounds in vivo.

  本发明涉及一种新型的取代螺环化合物。这些化合物可以抑制组蛋白去乙酰化酶，并适用于在选择性诱导末端分化、阻止肿瘤细胞的增殖和/或凋亡，从而抑制这些细胞的增殖中使用。因此，本发明的化合物可用于治疗具有肿瘤细胞增殖特征的患者。本发明的化合物还可用于预防和治疗TRX介导的疾病，例如自身免疫性、过敏性和炎症性疾病，并用于预防和/或治疗中枢神经系统（CNS）疾病，例如神经退行性疾病。本发明还提供了包含本发明化合物的药物组合物和这些药物组合物的安全剂量方案，这些方案易于遵循，并在体内产生治疗有效量的这些化合物。
• IAP BINDING COMPOUNDS
  申请人：Lundorf Mikkel Dybro

  公开号：US20110230419A1

  公开（公告）日：2011-09-22

  The present invention relates to compounds of formula (I), or pharmaceutically acceptable salts, solvates or prodrugs thereof, that bind to Inhibitor of Apoptosis Proteins (IAPs). The compounds of the invention may be used as diagnostic and therapeutic agents in the treatment of proliferative diseases, such as cancer, for promoting apoptosis in proliferating cells, and for sensitizing cells to inducers of apoptosis. The present invention furthermore provides a polymeric compound of formulas (VI) or (VII), comprising either at least two monomeric units of compounds of formula (I), or at least one monomeric unit of a compound of formula (I) and an entity E. The present invention further relates to pharmaceutical compositions comprising said compounds of formulas (I), (VI), and (VII) and the use of said compounds in medicine.

  本发明涉及式(I)的化合物，或其药学上可接受的盐、溶剂化合物或前药，其与凋亡抑制蛋白（IAPs）结合。本发明的化合物可用作诊断和治疗增生性疾病，例如癌症，促进增殖细胞的凋亡，并使细胞对凋亡诱导剂敏感。本发明还提供式(VI)或(VII)的聚合物化合物，其中包括至少两个式(I)的单体单位，或至少一个式(I)的单体单位和一个实体E。本发明还涉及包含上述化合物的药物组合物，以及在医学中使用上述化合物的用途。
• Spirocyclic Compounds
  申请人：Berk Scott C.

  公开号：US20090209566A1

  公开（公告）日：2009-08-20

  The present invention relates to a novel class of substituted spirocyclic compounds, represented by the following structural Formula: I Wherein A, B and D are independently selected from CR 1 2 , NR 1a , C(O) and O; E is selected from a bond, CR 1 2 , NR 1a , C(O) and O; wherein at least one of A, B, D or E is CR 1 2 ; and provided that when A is O, then E is not O; G is CR 1 2 ; R is selected from NH 2 and OH; These compounds can inhibit histone deacetylase and are suitable for use in selectively inducing termin differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The compounds of the invention may also be useful in the prevention and treatment of TRX-mediated diseases, such as autoimmune, allergic and inflammatory diseases, and in the prevention and/or treatment of diseases of the central nervous system (CNS), such as neurodegenerative diseases. The present invention further provides pharmaceutical compositions comprising the compounds of the instant invention and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of these compounds in vivo.

  本发明涉及一类新颖的取代螺环化合物，其结构式如下：I，其中A、B和D独立地选自CR12、NR1a、C（O）和O；E选自键、CR12、NR1a、C（O）和O；其中至少一个A、B、D或E为CR12；并且当A为O时，E不为O；G为CR12；R选自NH2和OH。这些化合物可以抑制组蛋白去乙酰化酶，并适用于在选择性诱导终止分化、阻止肿瘤细胞生长和/或凋亡，从而抑制这些细胞的增殖。因此，本发明的化合物在治疗具有肿瘤细胞增殖特征的患者中非常有用。本发明的化合物还可以用于预防和治疗TRX介导的疾病，例如自身免疫、过敏和炎症性疾病，以及中枢神经系统（CNS）疾病的预防和/或治疗，例如神经退行性疾病。本发明还提供了包含本发明化合物的药物组合物和这些药物组合物的安全剂量方案，易于遵循，并在体内产生治疗有效量的这些化合物。
• HETEROCYCLIC DERIVATIVES AS IAP BINDING COMPOUNDS
  申请人：Nuevolution A/S

  公开号：EP2318363A1

  公开（公告）日：2011-05-11