1-氮杂双环[3.2.1]辛烷-5-羧酸 | 119103-00-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: 1-氮杂双环[3.2.1]辛烷-5-羧酸
• 英文名称: 5-carboxy-1-azoniabicyclo[3.2.1]octane
• 英文别名: 1-Azabicyclo[3.2.1]octane-5-carboxylic acid
• CAS: 119103-00-3
• 化学式: C₈H₁₃NO₂
• mdl: MFCD18806583
• 分子量: 155.197
• InChiKey: SJUKNMWUZYVGSH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.875
• 拓扑面积：
  40.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-氮杂双环[3.2.1]辛烷-5-羧酸 在 4-二甲氨基吡啶 、 氯化亚砜 、 三氯溴甲烷 、 三乙胺 、 肼 作用下， 以 乙腈 为溶剂， 反应 5.75h， 生成 (+/-) 1-Azabicyclo[3.2.1]oct-5-ylhydrazine
  参考文献：
  名称：

  Substituent variation in azabicyclic triazole- and tetrazole-based muscarinic receptor ligands

  摘要：

  The effect of variation of the 1-azabicyclic substituent on the novel 1,2,3-triazol-4-yl-, 1,2,4-triazol-1-yl-, tetrazol-5-yl-, and tetrazol-2-yl-based muscarinic receptor ligands ha, been studied, and the exo-azabicyclic[2.2.1]hept-3-yl substituent was found to give the most potent and efficacious compounds. In addition, variation of the second substituent on 1,2,4-triazol-1-yl- and tetrazol-2-yl-based muscarinic receptor ligands has yielded a series of novel compounds with high potencies and efficacies, ranging from full agonists to antagonists. Small lipophilic electron withdrawing substituents give potent but low efficacy compounds, while small polar electron donating substituents give potent and efficacious compounds. The activity of these compounds is described in terms of a model of the receptor involving lipophilic and hydrogen bonding interactions. These compounds provide muscarinic ligands with high potency and a range of efficacies suitable for testing as candidate drugs in the treatment of Alzheimer's disease.

  DOI：

  10.1021/jm00091a007
• 作为产物：
  描述：

  ethyl 1-azabicyclo[3.2.1]octane-5-carboxylate 在 盐酸 作用下， 反应 11.0h， 生成 1-氮杂双环[3.2.1]辛烷-5-羧酸
  参考文献：
  名称：

  比较氮杂双环酯和恶二唑作为毒蕈碱受体的配体。

  摘要：

  与阿尔茨海默氏型痴呆症相关的认知缺陷与疾病中胆碱能功能的丧失之间的联系为检查毒蕈碱激动剂作为潜在治疗剂提供了基础。本文描述了新型的氮杂双环甲酯作为毒蕈碱受体配体的设计和合成。用3-甲基-1,2,4-恶二唑环取代甲酯可产生有效的代谢更稳定的毒蕈碱激动剂，能够穿透中枢神经系统。这些化合物相对于相应的甲酯通常显示出改善的亲和力。3-甲基1,2,4-恶二唑7b的亲和力是乙酰胆碱的4倍。关于氮杂双环的大小和几何形状以及杂芳族环的电子性质，讨论了受体亲和力。

  DOI：

  10.1021/jm00113a009

文献信息

• BENZOXAZOLE CARBOXAMIDE INHIBITORS OF POLY(ADP-RIBOSE)POLYMERASE (PARP)
  申请人：Chu Daniel

  公开号：US20090197863A1

  公开（公告）日：2009-08-06

  A compound having the structure set forth in Formula (I) or Formula (II): wherein the variables Y, R 1 , R 2 , R 3 , and R 4 are as defined herein. Provided herein are inhibitors of poly(ADP-ribose)polymerase activity. Also described herein are pharmaceutical compositions that include at least one compound described herein and the use of a compound or pharmaceutical composition described herein to treat diseases, disorders and conditions that are ameliorated by the inhibition of PARP activity.

  具有以下式(I)或式(II)所示结构的化合物： 其中变量Y，R1，R2，R3和R4如本文所定义。本文提供了聚(ADP-核糖)聚合酶活性的抑制剂。本文还描述了包括至少一种本文描述的化合物的药物组合物，以及使用本文描述的化合物或药物组合物治疗通过抑制PARP活性改善的疾病、疾病和症状。
• NOVEL INHIBITORS OF POLY(ADP-RIBOSE)POLYMERASE (PARP)
  申请人：CHU Daniel

  公开号：US20090062268A1

  公开（公告）日：2009-03-05

  A compound having the structure set forth in Formula (I): wherein the variables Y, R 1 , R 2 , R 3 , R 4 and R 5 are as defined herein. Compounds described herein are inhibitors of poly(ADP-ribose)polymerase activity. Also described herein are pharmaceutical compositions that include at least one compound described herein and the use of such compounds and pharmaceutical compositions to treat diseases, disorders and conditions that are ameliorated by the inhibition of PARP activity.

  具有以下式（I）所示结构的化合物： 其中变量Y，R1，R2，R3，R4和R5如本文所定义。本文描述的化合物是聚(ADP-核糖)聚合酶活性的抑制剂。本文还描述了包括至少一种本文描述的化合物的药物组合物，以及利用这些化合物和药物组合物治疗通过抑制PARP活性而改善的疾病、疾病和症状。
• [EN] 6-BRIDGED HETEROARYLDIHYDROPYRIMIDINES FOR THE TREATMENT AND PROPHYLAXIS OF HEPATITIS B VIRUS INFECTION<br/>[FR] HÉTEROARYLDIHYDROPYRIMIDINES PONTÉES EN POSITION 6 POUR LE TRAITEMENT ET LA PROPHYLAXIE D'UNE INFECTION PAR LE VIRUS DE L'HÉPATITE B
  申请人：HOFFMANN LA ROCHE

  公开号：WO2014184328A1

  公开（公告）日：2014-11-20

  The invention provides novel compounds having the general formula: wherein R1, R2, R3 and R4 are as defined in the description and in the claims, as well as or pharmaceutically acceptable salts, or tautomerism isomers, or enantiomers, or diastereomers thereof. The invention also contains compositions including the compounds and methods of using the compounds for the treatment or prophylaxis of hepatitis B virus infection.

  该发明提供了具有以下一般式的新化合物：其中R1、R2、R3和R4如描述和权利要求中所定义，以及其药学上可接受的盐，或互变异构体，或对映异构体，或非对映异构体。该发明还包括含有这些化合物的组合物以及使用这些化合物用于治疗或预防乙型肝炎病毒感染的方法。
• Design of [<i>R</i>-(<i>Z</i>)]-(+)-α-(Methoxyimino)-1-azabicyclo[2.2.2]octane-3-acetonitrile (SB 202026), a Functionally Selective Azabicyclic Muscarinic M1 Agonist Incorporating the <i>N</i>-Methoxy Imidoyl Nitrile Group as a Novel Ester Bioisostere
  作者：Steven M. Bromidge、Frank Brown、Frederick Cassidy、Michael S. G. Clark、Steven Dabbs、Michael S. Hadley、Julie Hawkins、Julia M. Loudon、Christopher B. Naylor、Barry S. Orlek、Graham J. Riley

  DOI：10.1021/jm9702903

  日期：1997.12.1

  Loss of cholinergic function is believed to be implicated in the cognitive decline associated with senile dementia of the Alzheimer type (SDAT). The disease is characterized by progressive loss of muscarinic receptors located on nerve terminals while postsynaptic muscarinic M1 receptors appear to remain largely intact. Muscarinic agonists acting directly on postsynaptic receptors offer the prospect of countering the cholinergic deficit in SDAT. This study describes a novel series of azabicyclic muscarinic agonists, which incorporate an oxime ether or modified oxime ether group as an ester bioisostere. Modification of the oxime ether function by the introduction of electron withdrawing groups led to the finding that the (Z)-N-methoxy imidoyl nitrile group serves as a stable methyl ester bioisostere. This culminated in the discovery of the quinuclidinyl N-methoxy imidoyl nitrile R-(+)-(Z)-5g which is a functionally selective muscarinic M1 partial agonist currently in phase III clinical trials for the treatment of SDAT. The selective profile of R-(+)-(Z)-5g can be rationalized in terms of the relative affinity of the compound at muscarinic receptor subtypes, the degree of agonist efficacy, and brain penetrancy.
• Bridgehead substituted azabicyclic derivatives
  申请人：BEECHAM GROUP PLC

  公开号：EP0287356B1

  公开（公告）日：1996-01-24