3-Aminomethyl-3-hydroxyquinuclidine-borane | 128653-87-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 奎宁环
• 英文名称: 3-Aminomethyl-3-hydroxyquinuclidine-borane
• 英文别名: (3-(aminomethyl)-3-hydroxy-1-azabicyclo[2.2.2]octan-1-yl)trihydroborate；(3-(aminomethyl)-3-hydroxy-1-ammoniobicyclo[2.2.2]octan-1-yl)trihydroborate；[3-(Aminomethyl)-3-hydroxy-1-azoniabicyclo[2.2.2]octan-1-yl]boranuide
• CAS: 128653-87-2
• 化学式: C₈H₁₉BN₂O
• 分子量: 170.063
• InChiKey: XQBMIPPKHMIEEJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.8
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  46.2
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-Aminomethyl-3-hydroxyquinuclidine-borane 在 盐酸 、 二氧化碳 、 sodium carbonate 、 caesium carbonate 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 丙酮 、 乙腈 为溶剂， 反应 1.2h， 生成 (3R)-N-[6-(1H-咪唑-1-基)-4-嘧啶基]螺[1-氮杂双环[2.2.2]辛烷-3,5-'(4'H)-噁唑]-2'-胺
  参考文献：
  名称：

  BMS-933043, a Selective α7 nAChR Partial Agonist for the Treatment of Cognitive Deficits Associated with Schizophrenia

  摘要：

  The therapeutic treatment of negative symptoms and cognitive dysfunction associated with schizophrenia is a significant unmet medical need. Preclinical literature indicates that a? neuronal nicotinic acetylcholine (nACh) receptor agonists may provide an effective approach to treating cognitive dysfunction in schizophrenia. We report herein the discovery and evaluation of 1c (BMS-933043), a novel and potent alpha 7 nACh receptor partial agonist with high selectivity against other nicotinic acetylcholine receptor subtypes (>100-fold) and the 5-HT3A receptor (>300-fold). In vivo activity was demonstrated in a preclinical model of cognitive impairment, mouse novel object recognition. BMS-933043 has completed Phase I clinical trials.

  DOI：

  10.1021/acsmedchemlett.7b00032
• 作为产物：
  描述：

  3-羟基喹洛啉-3-甲腈 在 硼烷 作用下， 以 四氢呋喃 为溶剂， 反应 12.0h， 以80%的产率得到3-Aminomethyl-3-hydroxyquinuclidine-borane
  参考文献：
  名称：

  Swain, Christopher J.; Kneen, Clare; Herbert, Richard, Journal of the Chemical Society. Perkin transactions I, 1990, # 11, p. 3183 - 3186

  摘要：

  DOI：

文献信息

• [EN] QUINUCLIDINE COMPOUNDS AS ALPHA-7 NICOTINIC ACETYLCHOLINE RECEPTOR LIGANDS<br/>[FR] COMPOSÉ DE QUINUCLIDINE COMME LIGANDS DU RÉCEPTEUR NICOTINIQUE ALPHA-7 DE L'ACÉTYLCHOLINE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2011053292A1

  公开（公告）日：2011-05-05

  The disclosure provides compounds of formula I, including their salts, as well as compositions and methods of using the compounds. The compounds are ligands for the nicotinic 7 receptor and may be useful for the treatment of various disorders of the central nervous system, especially affective and neurodegenerative disorders.

  该披露提供了公式I的化合物，包括它们的盐，以及使用这些化合物的组合物和方法。这些化合物是烟碱7受体的配体，可能对治疗中枢神经系统的各种紊乱，特别是情感和神经退行性疾病有用。
• QUINUCLIDINE COMPOUNDS AS ALPHA-7 NICOTINIC ACETYLCHOLINE RECEPTOR LIGANDS
  申请人：Cook, II James H.

  公开号：US20090270405A1

  公开（公告）日：2009-10-29

  The disclosure provides compounds of formula I, including their salts, as well as compositions and methods of using the compounds. The compounds are ligands for the nicotinic α7 receptor and may be useful for the treatment of various disorders of the central nervous system, especially affective and neurodegenerative disorders.

  该披露提供了公式I的化合物，包括它们的盐，以及使用这些化合物的组合物和方法。这些化合物是烟碱性α7受体的配体，可能对治疗中枢神经系统的各种疾病，特别是情感和神经退行性疾病，有用。
• Design and Synthesis of a New Series of 4-Heteroarylamino-1′-azaspiro[oxazole-5,3′-bicyclo[2.2.2]octanes as α7 Nicotinic Receptor Agonists. 1. Development of Pharmacophore and Early Structure–Activity Relationship
  作者：James Cook、F. Christopher Zusi、Ivar M. McDonald、Dalton King、Matthew D. Hill、Christiana Iwuagwu、Robert A. Mate、Haiquan Fang、Rulin Zhao、Bei Wang、Jingfang Cutrone、Baoqing Ma、Qi Gao、Ronald J. Knox、Michele Matchett、Lizbeth Gallagher、Meredith Ferrante、Debra Post-Munson、Thaddeus Molski、Amy Easton、Regina Miller、Kelli Jones、Siva Digavalli、Francine Healy、Kimberley Lentz、Yulia Benitex、Wendy Clarke、Joanne Natale、Judith A. Siuciak、Nicholas Lodge、Robert Zaczek、Rex Denton、Daniel Morgan、Linda J. Bristow、John E. Macor、Richard E. Olson

  DOI：10.1021/acs.jmedchem.6b01506

  日期：2016.12.22

  The design and synthesis of a series of quinuclidine-containing spirooxazolidines (“spiroimidates”) and their utility as α7 nicotinic acetylcholine receptor partial agonists are described. Selected members of the series demonstrated excellent selectivity for α7 over the highly homologous 5-HT3A receptor. Modification of the N-spiroimidate heterocycle substituent led to (1S,2R,4S)-N-isoquinolin-3-y

  描述了一系列含喹核苷的螺杂恶唑烷（“螺酰胺化物”）的设计和合成及其作为α7烟碱型乙酰胆碱受体部分激动剂的用途。该系列的选定成员对α7的选择性优于高度同源的5-HT 3A受体。所述的修饰Ñ导致（1 -spiroimidate杂环取代基小号，2 - [R，4小号- ）ñ -异喹啉-3-基）-4' ħ -4-氮杂螺[二环[2.2.2]辛烷-2,5-'恶唑] -2'-胺（BMS-902483），一种有效的α7部分激动剂，可改善临床前啮齿动物模型的认知度。
• JP5714745
  申请人：——

  公开号：——

  公开（公告）日：——