5-bromo-1-(1-methylpiperidin-4-yl)indoline | 1063408-02-5

• 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: 5-bromo-1-(1-methylpiperidin-4-yl)indoline
• 英文别名: 5-bromo-1-(1-methylpiperidin-4-yl)-2,3-dihydroindole
• CAS: 1063408-02-5
• 化学式: C₁₄H₁₉BrN₂
• 分子量: 295.222
• InChiKey: NTJUSSKBQBUYQF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  6.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-bromo-1-(1-methylpiperidin-4-yl)indoline 在 tris-(dibenzylideneacetone)dipalladium(0) 、 三叔丁基膦 lithium hexamethyldisilazane 、 盐酸 、 水 作用下， 以 四氢呋喃 、 hexanes 为溶剂， 反应 2.17h， 以36%的产率得到1-(1-methylpiperidin-4-yl)indolin-5-amine
  参考文献：
  名称：

  QUINOLONE AND TETRAHYDROQUINOLONE AND RELATED COMPOUNDS HAVING NOS INHIBITORY ACTIVITY

  摘要：

  本发明涉及抑制一氧化氮合酶（NOS）的喹诺酮、四氢喹啉和相关化合物，特别是那些选择性地抑制神经型一氧化氮合酶（nNOS）而不是其他NOS同工型的化合物。本发明的NOS抑制剂，单独或与其他药用活性剂结合使用，可用于治疗或预防各种医疗状况。

  公开号：

  US20080234237A1
• 作为产物：
  描述：

  N-甲基-4-哌啶酮 在 N-溴代丁二酰亚胺(NBS) 、 sodium cyanoborohydride 、 溶剂黄146 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 5-bromo-1-(1-methylpiperidin-4-yl)indoline
  参考文献：
  名称：

  Discovery of a potent, orally bioavailable and highly selective human neuronal nitric oxide synthase (nNOS) inhibitor, N-(1-(piperidin-4-yl)indolin-5-yl)thiophene-2-carboximidamide as a pre-clinical development candidate for the treatment of migraine

  摘要：

  We recently reported a series of 1,6-disubstituted indoline-based thiophene amidine compounds (5) as selective neuronal nitric oxide synthase (nNOS) inhibitors to mitigate the cardiovascular liabilities associated with hERG K+ channel inhibition (IC50 = 4.7 mu m) with previously reported tetrahydroquinoline-based selective nNOS inhibitors (4). The extended structure activity relationship studies within the indoline core led to the identification of 43 as a selection candidate for further evaluations. The in vivo activity in two different pain (spinal nerve ligation and migraine pain) models, the excellent physicochemical and pharmacokinetic properties, oral bioavailability (F-po = 91%), and the in vitro safety profile disclosed in this report make 43 an ideal candidate for further evaluation in clinical applications related to migraine pain. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.07.006

文献信息

• QUINOLONE AND TETRAHYDROQUINOLONE AND RELATED COMPOUNDS HAVING NOS INHIBITORY ACTIVITY
  申请人：MADDAFORD Shawn

  公开号：US20080234237A1

  公开（公告）日：2008-09-25

  The present invention features quinolones, tetrahydroquinolines, and related compounds that inhibit nitric oxide synthase (NOS), particularly those that selectively inhibit neuronal nitric oxide synthase (nNOS) in preference to other NOS isoforms. The NOS inhibitors of the invention, alone or in combination with other pharmaceutically active agents, can be used for treating or preventing various medical conditions.

  本发明涉及抑制一氧化氮合酶（NOS）的喹诺酮、四氢喹啉和相关化合物，特别是那些选择性地抑制神经型一氧化氮合酶（nNOS）而不是其他NOS同工型的化合物。本发明的NOS抑制剂，单独或与其他药用活性剂结合使用，可用于治疗或预防各种医疗状况。
• Quinolone and tetrahydroquinolone and related compounds having NOS inhibitory activity
  申请人：NeurAxon, Inc.

  公开号：US08173813B2

  公开（公告）日：2012-05-08

  The present invention features quinolones, tetrahydroquinolines, and related compounds that inhibit nitric oxide synthase (NOS), particularly those that selectively inhibit neuronal nitric oxide synthase (nNOS) in preference to other NOS isoforms. The NOS inhibitors of the invention, alone or in combination with other pharmaceutically active agents, can be used for treating or preventing various medical conditions.

  本发明涉及喹诺酮、四氢喹诺酮和相关化合物，它们抑制一氧化氮合酶（NOS），特别是选择性地抑制神经元一氧化氮合酶（nNOS）而不是其他NOS亚型。本发明的NOS抑制剂，单独或与其他药理活性剂联合使用，可用于治疗或预防各种医学疾病。
• Proline derivatives and use thereof as drugs
  申请人：Mitsubishi Tanabe Pharma Corporation

  公开号：EP1950199A1

  公开（公告）日：2008-07-30

  The present invention aims at providing compounds having therapeutic effects due to a DPP-IV inhibitory action, and satisfactory as pharmaceutical products. The present inventors have found that derivatives having a substituent introduced into the γ-position of proline represented by the formula (I) wherein each symbol is as defined in the specification, have a potent DPP-IV inhibitory activity, and completed the present invention by increasing the stability.

  本发明旨在提供因具有 DPP-IV 抑制作用而具有治疗效果的化合物，并提供令人满意的药物产品。 本发明者发现，在式 (I) 所代表的脯氨酸的 γ 位上引入取代基的衍生物 其中各符号如说明书中所定义，具有强效的 DPP-IV 抑制活性，并通过提高稳定性完成了本发明。
• QUINOLONE AND TETRAHYDROQUINOLINE AND RELATED COMPOUNDS HAVING NOS INHIBITORY ACTIVITY
  申请人：Neuraxon Inc.

  公开号：EP2139886A1

  公开（公告）日：2010-01-06
• US8173813B2
  申请人：——

  公开号：US8173813B2

  公开（公告）日：2012-05-08