Z-(R)-(-)-1-Azabicyclo[2.2.1]heptan-3-one | 142034-96-6

• 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: Z-(R)-(-)-1-Azabicyclo[2.2.1]heptan-3-one
• 英文别名: (R)-1-azabicyclo[2.2.1]heptan-3-one；(1S,4R)-1-azabicyclo[2.2.1]heptan-3-one；R-(Z)-1-azabicyclo[2.2.1]heptan-3-one；(4R)-1-azabicyclo[2.2.1]heptan-3-one
• CAS: 142034-96-6
• 化学式: C₆H₉NO
• 分子量: 111.144
• InChiKey: VZPRMKOCTSUHCR-RXMQYKEDSA-N

物化性质

• 沸点：
  183.9±23.0 °C(Predicted)
• 密度：
  1.17±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  8
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  Z-(R)-(-)-1-Azabicyclo[2.2.1]heptan-3-one 在 盐酸羟胺 作用下， 以 甲醇 、 sodium carbonate 为溶剂， 生成 (R)-(Z)-1-Azabicyclo[2.2.1]heptan-3-one oxime
  参考文献：
  名称：

  Preparation of stereochemically pure oximes with muscarinic activity

  摘要：

  本发明是选择性制备Z-肟和O-烷基化1-氮杂双环[2.2.1]庚烷-3-酮和1-氮杂双环[2.2.2]庚烷-3-酮肟，以制备具有毒蕈碱活性的化合物。该过程能够进行工业规模化生产，因为它提供更好的产量和制备的便利性。本发明还描述了中间体。

  公开号：

  US05514812A1
• 作为产物：
  描述：

  (+/-)-exo-azabicyclo<2.2.1>heptan-3-ol 在 草酰氯 、 二甲基亚砜 、 三乙胺 作用下， 生成 Z-(R)-(-)-1-Azabicyclo[2.2.1]heptan-3-one
  参考文献：
  名称：

  3-取代的1-氮杂双环[2.2.1]庚烷的绝对构型†

  摘要：

  通过氮杂酒石酸氢盐的分步结晶，拆分了l-氮杂双环[2.2.1]庚基-3- exo - ol（2）。对映体（+）-和（-）- 2分别被氧化为酮（-）- 4和（+）- 4（方案）。CD光谱法表明（-）- 4具有（1 R，4 S）-构型。这种绝对构型由衍生物（+）-（1 R，4 R）-3-（1,3-二噻吩-2-亚烷基）-1-氮杂双环[2.2.1]的单晶X射线衍射证实。-庚烷（（+）- 5）。

  DOI：

  10.1002/hlca.19920750210

文献信息

• MULTI-CYCLIC COMPOUNDS
  申请人：KIMURA Teiji

  公开号：US20090062529A1

  公开（公告）日：2009-03-05

  A compound represented by the formula (I): or a pharmacologically acceptable salt thereof, wherein Ar 1 represents an imidazolyl group or the like which may be substituted with a C1-6 alkyl group, Ar 2 represents a phenyl group or the like which may be substituted with a C1-6 alkoxy group, X 1 represents a double bond or the like and Het represents a triazolyl group or the like which may be substituted with a C1-6 alkyl group or the like, is effective as a therapeutic or prophylactic agent for a disease caused by Aβ.

  一种由化学式(I)表示的化合物或其药理学可接受的盐，其中Ar1代表可用C1-6烷基基团取代的咪唑基团或类似基团，Ar2代表可用C1-6烷氧基团取代的苯基团或类似基团，X1代表双键或类似基团，Het代表可用C1-6烷基基团或类似基团取代的三唑基团或类似基团，对由Aβ引起的疾病具有治疗或预防作用。
• [EN] IMIDAZOLYLPYRAZINE DERIVATIVES<br/>[FR] DÉRIVÉS D'IMIDAZOLYLPYRAZINE
  申请人：EISAI R&D MAN CO LTD

  公开号：WO2010098495A1

  公开（公告）日：2010-09-02

  To provide a novel low-molecular-weight compound that inhibits the production of amyloid-β (Aβ ). A compound represented by the formula [I]: or a pharmacologically acceptable salt or ester thereof, wherein R1 and R2 are the same or different and each represent a substituent selected from the following Substituent Group a1; m represents an integer of 0 to 3; n represents an integer of 0 to 2; X1 represents a single bond or the like; X2 represents a single bond or the like; Ring A represents a five-membered aromatic heterocyclic group or the like which contains two or more nitrogen atoms and may have 1 to 3 substituents selected from the following Substituent Group b1; and Ring B represents a monocyclic or fused cyclic aromatic ring group such as the formula [2] which may have 1 to 3 substituents selected from the following Substituent Group c1, is effective as a therapeutic agent for a disease such as Alzheimer's disease. Substituent Group a1: a C1-6 alkyl group and the like Substituent Group b1: a C1-6 alkyl group and the like Substituent Group c1: an amino group and the like

  提供一种新型低分子量化合物，该化合物能够抑制淀粉样蛋白-β（Aβ）的产生。表示为化学式[I]的化合物，或其药理学上可接受的盐或酯，其中R1和R2相同或不同，每个代表以下取代基团a1中选择的取代基；m代表0到3的整数；n代表0到2的整数；X1代表单键或类似物；X2代表单键或类似物；环A代表含有两个或更多氮原子并且可能具有1到3个取代基团b1中选择的取代基的五元芳香杂环基团或类似物；环B代表可能具有1到3个取代基团c1中选择的取代基的单环或融合环芳香环基团，如化学式[2]所示，对于阿尔茨海默病等疾病具有治疗作用。取代基团a1：C1-6烷基基团等；取代基团b1：C1-6烷基基团等；取代基团c1：氨基团等。
• 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。
• Ester bio-isosteres: synthesis of oxadiazolyl-1-azabicyclo[2.2.1]heptanes as muscarinic agonists
  作者：John Saunders、Angus M. MacLeod、Kevin Merchant、Graham A. Showell、Roger J. Snow、Leslie J. Street、Raymond Baker

  DOI：10.1039/c39880001618

  日期：——

  The methyl ester functionality in arecoline and related esters has been replaced by 1,2,4-oxadiazole to generate the most potent and efficacious muscarinic agonists known.

  槟榔碱和相关酯中的甲基酯官能团已被1,2,4-恶二唑取代，以生成已知的最有效和最有效的毒蕈碱激动剂。
• In vitro and in vivo evaluation of the subtype-selective muscarinic agonist PD 151832
  作者：J. Jaen、S. Barrett、M. Brann、M. Callahan、R. Davis、P. Doyle、D. Eubanks、D. Lauffer、L. Lauffer、W. Lipinski、D. Moreland、C. Nelson、C. Raby、R. Schwarz、C. Spencer、H. Tecle

  DOI：10.1016/0024-3205(95)00019-3

  日期：1995.2

  PD 151832 is a potent partial muscarinic agonist that displays a high level of functional selectivity for the muscarinic m1 receptor subtype, as evidenced by its selective stimulation of PI turnover and cellular metabolic activity in transfected Hm1-CHO cells at concentrations that produce minimal stimulation of other cloned human muscarinic receptors. PD 151832 enhanced the amplification of Hm1-transfected

  PD 151832是一种强效的部分毒蕈碱激动剂，对毒蕈碱m1受体亚型显示出高水平的功能选择性，这一点可通过其对PI转染的选择性刺激和对Hm1-CHO细胞的细胞代谢活性的选择性刺激来证明，其浓度对其他药物几乎没有刺激克隆的人毒蕈碱受体。PD 151832增强了Hm1转染的NIH-3T3细胞的扩增，其浓度低于在Hm2或Hm3转染的细胞中产生类似作用所需的浓度。PD 151832的功能性m1选择性与其对小鼠水迷宫性能的改善相一致，其剂量远低于产生周围副交感神经副作用所需的剂量。