4-(5,6-dichloro-1H-indol-2-yl)-3-methoxy-N-(1,2,2,6,6-pentamethylpiperidin-4-yl)benzamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 4-(5,6-dichloro-1H-indol-2-yl)-3-methoxy-N-(1,2,2,6,6-pentamethylpiperidin-4-yl)benzamide
• 化学式: C₂₆H₃₁Cl₂N₃O₂
• 分子量: 488.4
• InChiKey: VSFGXJYLNSTQIV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  33
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  57.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  3-methoxy-4-(5,6-dichloro-1H-indol-2-yl)-benzoic acid 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 N-羟基-7-氮杂苯并三氮唑 、 4-氨基-1,2,2,6,6-五甲基哌啶 在 乙酸乙酯 、 水 、 magnesium sulfate 、 SiO2 、 Dichloromethane methanol ammonium hydroxide 、 异丙醚 作用下， 以 N,N-二甲基甲酰胺 、 水 为溶剂， 反应 18.0h， 以to afford 0.13 g (0.26 mmol. yield 59%) of the title compound, mp=260° C.的产率得到4-(5,6-dichloro-1H-indol-2-yl)-3-methoxy-N-(1,2,2,6,6-pentamethylpiperidin-4-yl)benzamide
  参考文献：
  名称：

  Indole derivatives useful A.O. for the treatment of osteoporosis

  摘要：

  化合物的化学式为（I）的化合物，或其盐，或其溶剂化合物，其中：A代表可选取代的芳基或可选取代的杂环基；Ra代表- CO-NRsRt，其中Rs和Rt各自独立地代表氢，烷基，取代烷基，可选取代烯基，可选取代芳基，可选取代芳基烷基，可选取代杂环基或可选取代杂环基烷基，或Rs和Rt与它们所连接的氮一起形成杂环基；R1和R2各自独立地代表氢，羟基，氨基，烷氧基，可选取代的芳氧基，可选取代苯基氧基，烷基氨基，二烷基氨基，卤素，三氟甲基，三氟甲氧基，硝基，烷基，羧基，羧甲酰氧基，氨基甲酰基，烷基氨基甲酰基，或R1和R2一起代表亚甲二氧基，羰基二氧基或羰基二氨基；R3代表氢，烷酰基，烷基，氨基烷基，羟基烷基，羧基烷基，羧甲酰氧基烷基，氨基甲酰基或烷基磺酰基和芳基磺酰基；一种制备此类化合物的方法，一种含有此类化合物的制药组合物以及此类化合物或组合物在医学上的用途。

  公开号：

  US06506758B2

文献信息

• [EN] INDOLE DERIVATIVES AND THEIR USE FOR THE TREATMENT OF OSTEOPOROSIS AMONGST OTHER APPLICATIONS<br/>[FR] DERIVES DE L'INDOLE ET LEUR UTILISATION POUR TRAITER L'OSTEOPOROSE ET D'AUTRES PATHOLOGIES
  申请人：SMITHKLINE BEECHAM SPA

  公开号：WO2001002388A1

  公开（公告）日：2001-01-11

  A compound of formula (I) or a salt thereof, or a solvate thereof, wherein: R1 and R2 each independently represents C1-6alkoxy or halo; R3 and R4 each independently represents hydrogen, C1-6alkoxy, arylC1-6alkoxy, hydroxy, carboxyC1-6alkoxy, hydroxyC1-6alkoxy, dihydroxyC1-6alkoxy, mono- and di-(C1-6alkyl)aminoC1-6alkoxy or aminoC1-6alkoxy, and R5 represents -NRsRt wherein Rs and Rt each independently represent hydrogen, unsubstituted or substituted C1-6alkyl, or unsubstituted or substituted heterocyclyl, a process for the preparation of such a compound, a pharmaceutical composition containing such a compound and the use of the compound or composition in medicine. Particular indole compounds are selective for mammalian osteoclasts, acting to selectively inhibit their bone resorbing activity. These compounds are therefore considered to be particularly useful for the treatment and/or prophylaxis of diseases associated with loss of bone mass, such as osteoporosis and related osteopenic diseases, Paget's disease, hyperparathyroidism and related diseases. These compounds are also considered to possess antitumour activity, antiviral activity (for example against Semliki Forest, Vesicular Stomatitis, Newcastle Disease, Influenza A and B, HIV viruses), antiulcer activity (for example the compounds may be useful for the treatment of chronic gastritis and peptic ulcer induced by Helicobacter pylori) immunosuppressant activity, antilipidemic activity, antiatherosclerotic activity and to be useful for the treatment of AIDS and Alzheimer's disease. Furthermore, these compounds are also considered useful in inhibiting angiogenesis i.e. the formation of new blood vessels which is observed in various types of pathological conditions (angiogenic diseases) such as rheumatoid arthritis, diabetic retinopathy, psoriasis and solid tumours.

  化合物(I)的公式或其盐或溶剂化物，其中：R1和R2各自独立地表示C1-6烷氧基或卤素；R3和R4各自独立地表示氢、C1-6烷氧基、芳基C1-6烷氧基、羟基、羧基C1-6烷氧基、羟基C1-6烷氧基、二羟基C1-6烷氧基、单烷基和双烷基(C1-6)氨基C1-6烷氧基或氨基C1-6烷氧基，R5表示-NRsRt，其中Rs和Rt各自独立地表示氢、未取代或取代的C1-6烷基或未取代或取代的杂环基，制备此类化合物的方法，包含这种化合物的制药组合物以及该化合物或组合物在医学上的用途。特定的吲哚化合物对哺乳动物骨吸收细胞具有选择性，能够选择性地抑制它们的骨吸收活性。因此，这些化合物被认为特别适用于治疗和/或预防与骨量丢失相关的疾病，例如骨质疏松症和相关的骨质疏松症、帕吉特病、甲状旁腺功能亢进症和相关疾病。这些化合物也被认为具有抗肿瘤活性、抗病毒活性（例如对森林脑炎、口蹄疫、新城疫、甲型和乙型流感病毒、HIV病毒等），抗溃疡活性（例如这些化合物可用于治疗由幽门螺杆菌引起的慢性胃炎和消化性溃疡），免疫抑制活性、降脂活性、抗动脉粥样硬化活性，并可用于治疗艾滋病和阿尔茨海默病。此外，这些化合物还被认为在抑制血管生成（即在各种病理情况下观察到的新血管形成）方面具有用途，例如类风湿性关节炎、糖尿病性视网膜病变、牛皮癣和实体瘤等血管生成性疾病。
• Indole derivatives and their use for the treatment of osteoporosis amongst other applications
  申请人：——

  公开号：US20040235930A1

  公开（公告）日：2004-11-25

  A compound of formula (I) or a salt thereof, or a solvate thereof, wherein: R 1 and R 2 each independently represents C 1-6 alkoxy or halo; R 3 and R 4 each independently represents hydrogen, C 1-6 alkoxy, arylC 1-6 alkoxy, hydroxy, carboxyC 1-6 alkoxy, hydroxyC 1-6 alkoxy, dihydroxyC 1-6 alkoxy, mono- and di-(C 1-6 alkyl)aminoC 1-6 alkoxy or aminoC 1-6 alkoxy, and R 5 represents —NR s R t wherein R s and R t each independently represent hydrogen, unsubstituted or substituted C 1-6 alkyl, or unsubstituted or substituted heterocyclyl, a process for the preparation of such a compound, a pharmaceutical composition containing such a compound and the use of the compound or composition in medicine. Particular indole compounds are selective for mammalian osteoclasts, acting to selectively inhibit their bone resorbing activity. These compounds are therefore considered to be particularly useful for the treatment and/or prophylaxis of diseases associated with loss of bone mass, such as osteoporosis and related osteopenic diseases, Paget's disease, hyperparathyroidism and related diseases. These compounds are also considered to possess antitumour activity, antiviral activity (for example against Semliki Forest, Vesicular Stomatitis, Newcastle Disease, Influenza A and B, HIV viruses), antiulcer activity (for example the compounds may be useful for the treatment of chronic gastritis and peptic ulcer induced by Helicobacter pylori ), immunosuppressant activity, antilipidemic activity, antiatherosclerotic activity and to be useful for the treatment of AIDS and Alzheimer's disease. Furthermore, these compounds are also considered useful in inhibiting angiogenesis, i.e., the formation of new blood vessels which is observed in various types of pathological conditions (angiogenic diseases) such as rheumatoid arthritis, diabetic retinopathy, psoriasis and solid tumours.

  化合物公式（I）或其盐或其溶剂化物，其中：R1和R2各自独立表示C1-6烷氧基或卤素基；R3和R4各自独立表示氢、C1-6烷氧基、芳基C1-6烷氧基、羟基、羧基C1-6烷氧基、羟基C1-6烷氧基、二羟基C1-6烷氧基、单-和双-(C1-6烷基)氨基C1-6烷氧基或氨基C1-6烷氧基，R5表示-NRsRt，其中Rs和Rt各自独立表示氢、未取代或取代C1-6烷基或未取代或取代杂环基，制备此类化合物的方法，含有此类化合物的制药组合物以及该化合物或组合物在医学上的应用。特定的吲哚化合物对哺乳动物破骨细胞选择性作用，具有选择性地抑制它们的骨吸收活性。因此，认为这些化合物特别适用于治疗和/或预防与骨量丢失相关的疾病，如骨质疏松症和相关的骨质疏松病、帕吉特病、甲状旁腺功能亢进症和相关疾病。认为这些化合物还具有抗肿瘤活性、抗病毒活性（例如对森林脑炎、口疮病毒、新城疫、甲型和乙型流感病毒、HIV病毒等），抗溃疡活性（例如这些化合物可以用于治疗由幽门螺杆菌引起的慢性胃炎和消化性溃疡），免疫抑制活性、抗脂质血症活性、抗动脉粥样硬化活性，并且对治疗艾滋病和阿尔茨海默病有用。此外，认为这些化合物还有抑制血管生成的作用，即在各种病理情况下（血管生成性疾病），如类风湿性关节炎、糖尿病视网膜病变、银屑病和实体瘤中观察到的新血管形成。
• INDOLE DERIVATIVES USEFUL A.O. FOR THE TREATMENT OF OSTEOPOROSIS
  申请人：NIKEM RESEARCH S.R.L.

  公开号：EP1042316B1

  公开（公告）日：2005-02-09
• INDOLE DERIVATIVES AND THEIR USE FOR THE TREATMENT OF OSTEOPOROSIS AMONGST OTHER APPLICATIONS
  申请人：GlaxoSmithKline S.p.A.

  公开号：EP1212317A1

  公开（公告）日：2002-06-12
• US6506758B2
  申请人：——

  公开号：US6506758B2

  公开（公告）日：2003-01-14