rac-(1R,3R,4S)-3-hydroxy-1-azabicyclo[2.2.1]heptane-3-carbonitrile | 128200-34-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: rac-(1R,3R,4S)-3-hydroxy-1-azabicyclo[2.2.1]heptane-3-carbonitrile
• 英文别名: (3R,4S)-3-hydroxy-1-azabicyclo[2.2.1]heptane-3-carbonitrile
• CAS: 128200-34-0；128200-35-1；144335-22-8
• 化学式: C₇H₁₀N₂O
• 分子量: 138.169
• InChiKey: WMIKGIIJWWWYPK-BQBZGAKWSA-N

物化性质

• 沸点：
  295.4±35.0 °C(Predicted)
• 密度：
  1.30±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  47.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  rac-(1R,3R,4S)-3-hydroxy-1-azabicyclo[2.2.1]heptane-3-carbonitrile 在 盐酸 、 水 、 N,N'-二异丙基碳二亚胺 作用下， 以 四氢呋喃 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 96.83h， 生成 rac-(1R,3R,4S)-N-(6-methoxybenzo[d]thiazol-2-yl)-4'H-1-azaspiro[bicyclo[2.2.1]heptane-3,5'-oxazol]-2'-amine
  参考文献：
  名称：

  [EN] AZABICYCLO[2.2.1] HEPTANE COMPOUNDS AS ALPHA-7 NICOTINIC ACETYLCHOLINE RECEPTOR LIGANDS
  [FR] COMPOSÉS D'AZABICYCLO[2.2.1]HEPTANE EN TANT QUE LIGANDS DU RÉCEPTEUR ALPHA-7 NICOTINIQUE D'ACÉTYLCHOLINE

  摘要：

  该披露提供了公式I的化合物，包括Ia、Ib、Ic或Id，包括它们的盐，以及使用这些化合物的组合物和方法。这些化合物是尼古丁α7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（公式I）有用。

  公开号：

  WO2011056503A1
• 作为产物：
  描述：

  1-氮杂双环[2.2.1]-3-庚酮盐酸盐 在 氰化钠 作用下， 以 水 为溶剂， 生成 rac-(1R,3R,4S)-3-hydroxy-1-azabicyclo[2.2.1]heptane-3-carbonitrile
  参考文献：
  名称：

  Synthesis of indole oxazolines, potent 5-HT3 antagonists

  摘要：

  DOI：

  10.1016/s0040-4039(00)97385-4

文献信息

• 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。
• Synthesis of azanorbornyl-spirodioxolanes related to the muscarinic agonist AF30.
  作者：Angus M. MacLeod、Raymond Baker、Richard Herbert、Richard T. Lewis、Manuel Medarde、Leslie J. Street

  DOI：10.1016/s0040-4039(00)74693-4

  日期：1992.7

  1-Azabicyclo[2.2.1.]heptane spirodioxolanes have been prepared with a difference in the ease of intramolecular SN2 displacement giving an apparent epimer selectivity in the formation of fluorinated derivatives.

  已经制备了1-氮杂双环[2.2.1。]庚烷螺二氧杂环戊烷，其分子内SN 2置换的难易程度有所不同，从而在形成氟化衍生物时具有明显的差向异构体选择性。
• Novel 5-HT3 antagonists: indol-3-ylspiro(azabicycloalkane-3,5'(4'H)oxazoles)
  作者：C. J. Swain、R. Baker、C. Kneen、R. Herbert、J. Moseley、J. Saunders、E. M. Seward、G. I. Stevenson、M. Beer

  DOI：10.1021/jm00084a007

  日期：1992.3

  The synthesis and biochemical evaluation of a series of spirofused indole oxazoline 5-HT3 antagonists is described in which the oxazoline ring acts as a bioisosteric replacement for esters and amides. The effect of substitution about the indole ring has shown the steric limitations of the aromatic binding site. Incorporation of a variety of azabicyclic systems within the rigid spirofused framework has allowed the definition of a binding model which incorporates a number of known antagonists and agonists. In this model steric constraints limit substitution around the indole ring although there is some bulk tolerance at the 1- and 2-positions. The importance of constraining the basic nitrogen within an azabicyclic system is underlined by comparison with the monocyclic piperidine. The highest affinity was observed for those compounds in which the basic nitrogen occupies a bridgehead position, the most potent analogue in this group being the azabicyclic [3.3.1] system (pIC50 = 8.95), suggesting lipophilic interactions may play a role in increasing affinity. A suggested model for agonist binding is included in which the basic nitrogens are superimposed and the 5-hydroxyl group of 5-HT is superimposed on the H-bond-accepting atom of the heterocyclic linking group.
• AZABICYCLO[2.2.1]HEPTANE COMPOUNDS AS ALPHA-7 NICOTINIC ACETYLCHOLINE RECEPTOR LIGANDS
  申请人：Bristol-Myers Squibb Company

  公开号：EP2493893A1

  公开（公告）日：2012-09-05
• US8278320B2
  申请人：——

  公开号：US8278320B2

  公开（公告）日：2012-10-02