5-bromo-1-(1,4-dioxaspiro[4.5]decan-8-yl)indoline | 1063410-07-0

• 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-(1,4-dioxaspiro[4.5]decan-8-yl)indoline
• 英文别名: 5-bromo-1-(1,4-dioxaspiro[4.5]decan-8-yl)-2,3-dihydroindole
• CAS: 1063410-07-0
• 化学式: C₁₆H₂₀BrNO₂
• 分子量: 338.244
• InChiKey: PDBNSTRQIOIOPZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  21.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-bromo-1-(1,4-dioxaspiro[4.5]decan-8-yl)indoline 在 盐酸 、 tris-(dibenzylideneacetone)dipalladium(0) 、 三叔丁基膦 、 四丁基氟化铵 、 sodium cyanoborohydride 、 溶剂黄146 、 三乙胺 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙醇 、 正己烷 、 水 、 丙酮 为溶剂， 反应 16.0h， 生成 cis-tert-butylmethyl(4-(5-(thiophene-2-carboximidamido)indolin-1-yl)cyclohexyl)carbamate
  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
• 作为产物：
  描述：

  1-(1,4-dioxaspiro[4.5]decan-8-yl)indoline 在 N-溴代丁二酰亚胺(NBS) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 以90%的产率得到5-bromo-1-(1,4-dioxaspiro[4.5]decan-8-yl)indoline
  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

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。
• INDOLE AND BENZOMORPHOLINE DERIVATIVES AS MODULATORS OF METABOTROPIC GLUTAMATE RECEPTORS
  申请人：Cid-Nunez Jose Maria

  公开号：US20110275624A1

  公开（公告）日：2011-11-10

  The present invention relates to novel compounds, in particular novel indole and benzomorpholine derivatives according to Formula (I) wherein all radicals are as defined in the application and claims. The compounds according to the invention are positive allosteric modulators of metabotropic receptors-subtype 2 (“mGluR2”) which are useful for the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which the mGluR2 subtype of metabotropic receptors is involved. In particular, such diseases are central nervous system disorders selected from the group of anxiety, schizophrenia, migraine, depression, and epilepsy. The invention is also directed to pharmaceutical compositions and processes to prepare such compounds and compositions, as well as to the use of such compounds for the prevention and treatment of such diseases in which mGluR2 is involved.

  本发明涉及一种新型化合物，特别是根据公式（I）中定义的所有基团的新型吲哚和苯并吗啡衍生物。本发明的化合物是代谢型受体亚型2（“mGluR2”）的正向变构调节剂，可用于治疗或预防与谷氨酸功能障碍有关的神经和精神障碍以及涉及代谢型受体亚型2的疾病。特别是，这些疾病是从焦虑、精神分裂症、偏头痛、抑郁症和癫痫等中枢神经系统疾病中选择的。本发明还涉及制备这种化合物和组合物的制药组合物和制备过程，以及使用这种化合物预防和治疗涉及mGluR2的这些疾病。
• 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。
• US8173813B2
  申请人：——

  公开号：US8173813B2

  公开（公告）日：2012-05-08
• [EN] QUINOLONE AND TETRAHYDROQUINOLINE AND RELATED COMPOUNDS HAVING NOS INHIBITORY ACTIVITY<br/>[FR] QUINOLONES ET TÉTRAHYDROQUINOLÉINES ET COMPOSÉS APPARENTÉS AYANT UNE ACTIVITÉ INHIBITRICE DE NOS
  申请人：NEURAXON INC

  公开号：WO2008116308A1

  公开（公告）日：2008-10-02

  [EN] 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.
  [FR] La présente invention porte sur des quinolones, des tétraydroquinoléines et des composés apparentés qui inhibent l'oxyde nitrique synthase (NOS), en particulier sur celles et ceux qui inhibent de façon sélective l'oxyde nitrique synthase neuronal (nNOS) de préférence à d'autres isoformes de NOS. Les inhibiteurs de NOS de l'invention, individuellement ou en combinaison avec d'autres agents pharmaceutiquement actifs, peuvent être utilisés pour traiter ou prévenir divers états médicaux.