(1R,4R)-2,5-二氮杂双环<2.2.1>庚烷 | 116183-84-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: (1R,4R)-2,5-二氮杂双环<2.2.1>庚烷
• 中文别名: (1R,4R)-2,5-二氮杂双环[2.2.1]庚烷
• 英文名称: (1R,4R)-2,5-diazabicyclo<2.2.1>heptane
• 英文别名: (1R,4R)-2,5-diazabicyclo[2.2.1]heptane
• CAS: 116183-84-7
• 化学式: C₅H₁₀N₂
• 分子量: 98.1478
• InChiKey: UKHJNJFJCGBKSF-RFZPGFLSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  7
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  24.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3,7-dichloro-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one 、 (1R,4R)-2,5-二氮杂双环<2.2.1>庚烷 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 生成 7-chloro-3-[(1R,4R)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2-one
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of 3-[4-(2-Hydroxyethyl)piperazin-1-yl]-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one, a Potent, Orally Active, Brain Penetrant Inhibitor of Phosphodiesterase 5 (PDE5)

  摘要：

  We recently described a novel series of aminopyridopyrazinones as PDE5 inhibitors. Efforts toward optimization of this series culminated in the identification of 3-[4-(2-hydroxyethyl)piperazin-1-yl]-7-(6-methoxypyridin-3-yl)- 1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one, which possessed an excellent potency and selectivity profile and demonstrated robust in vivo blood pressure lowering in a spontaneously hypertensive rat (SHR) model. Furthermore, this compound is brain penetrant and will be a useful agent for evaluating the therapeutic potential of central inhibition of PDE5. This compound has recently entered clinical trials.

  DOI：

  10.1021/jm901781q
• 作为产物：
  描述：

  (1R,4R)-6-benzyl-3,6-diazabicyclo[2.2.1]heptane dihydrobromide 以91%的产率得到
  参考文献：
  名称：

  WEBER, ABRAHAM;BOUZARD, DANIEL;ESSIZ, MUNIR;CESARE, PIERRE D.;JACQUET, JE+

  摘要：

  DOI：

文献信息

• Synthesis and evaluation of potent pyrrolidine H3 antagonists
  作者：Anil Vasudevan、Scott E. Conner、Robert G. Gentles、Ramin Faghih、Huaqing Liu、Wesley Dwight、Lynne Ireland、Chae Hee Kang、Timothy A. Esbenshade、Youssef L. Bennani、Arthur A. Hancock

  DOI：10.1016/s0960-894x(02)00685-6

  日期：2002.11

  The synthesis and biological evaluation of novel antagonists of the rat H(3) receptor are described. These compounds differ from prototypical H(3) antagonists in that they do not contain an imidazole moiety, but rather a substituted aminopyrrolidine moiety. A systematic modification of the substituents on the aminopyrrolidine ring was performed using pre-formatted precursor sets, where applicable,

  合成和生物学评估大鼠H（3）受体的新型拮抗剂。这些化合物不同于典型的H（3）拮抗剂，因为它们不包含咪唑部分，而是取代的氨基吡咯烷部分。使用预格式化的前体组（适用时）对氨基吡咯烷环上的取代基进行了系统的修饰，以提供对H（3）受体具有高亲和力和选择性的几种化合物。
• Fluoronaphthyridines and -quinolones as antibacterial agents. 3. Synthesis and structure-activity relationships of new 1-(1,1-dimethyl-2-fluoroethyl), 1-[1-methyl-1-(fluoromethyl)-2-fluoroethyl], and 1-[1,1-(difluoromethyl)-2-fluoroethyl] substituted derivatives
  作者：P. Remuzon、D. Bouzard、P. Di Cesare、M. Essiz、J. P. Jacquet、J. R. Kiechel、B. Ledoussal、R. E. Kessler、J. Fung-Tomc

  DOI：10.1021/jm00105a006

  日期：1991.1

  prepared. Structure-activity relationship (SAR) studies indicated that the in vitro antibacterial potency was the following order: 1-(1,1-dimethyl-2-fluoroethyl) greater than 1-[1-methyl-1-(fluoromethyl)-2-fluoroethyl] greater than 1-[1,1-(difluoromethyl)-2-fluoroethyl] substituents. In the quinolone series the monofluoro-tert-butyl derivatives were found to possess better in vitro antibacterial activity

  制备了一系列新型的N-1-（单-，-（二-和-（三氟叔丁基）喹诺酮）和-萘吡啶类化合物，结构-活性关系（SAR）研究表明，体外抗菌能力是顺序如下：1-（1,1-二甲基-2-氟乙基）大于1- [1-甲基-1-（氟甲基）-2-氟乙基]大于1- [1,1-（二氟甲基）-2-在喹诺酮系列中，发现单氟叔丁基衍生物具有比非氟化叔丁基等效物更好的体外抗菌活性，其中1-氟叔丁基取代衍生物的体内PD50值反映了药代动力学行为和口服吸收不完全。
• Tricyclic aminopyrimidine histamine H4 receptor antagonists
  作者：Brad M. Savall、Laurent Gomez、Frank Chavez、Michael Curtis、Steven P. Meduna、Aaron Kearney、Paul Dunford、Jeffery Cowden、Robin L. Thurmond、Cheryl Grice、James P. Edwards

  DOI：10.1016/j.bmcl.2011.08.014

  日期：2011.11

  This report discloses the development of a series of tricyclic histamine H-4 receptor antagonists. Starting with a low nanomolar benzofuranopyrimidine HTS hit devoid of pharmaceutically acceptable properties, we navigated issues with metabolism and solubility to furnish a potent, stable and water soluble tricyclic histamine H-4 receptor antagonist with desirable physiochemical parameters which demonstrated efficacy a mouse ova model. (C) 2011 Elsevier Ltd. All rights reserved.
• Fluoronaphthyridines as antibacterial agents. 4. Synthesis and structure-activity relationships of 5-substituted 6-fluoro-7-(cycloalkylamino)-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acids
  作者：D. Bouzard、P. Di Cesare、M. Essiz、J. P. Jacquet、B. Ledoussal、P. Remuzon、R. E. Kessler、J. Fung-Tomc

  DOI：10.1021/jm00081a013

  日期：1992.2

  A series of 5-substituted-6-fluoro-7-(cycloalkylamino)-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acids have been prepared and tested for their in vitro and in vivo antibacterial activities. The 5-methyl group gave better in vitro activity with the 1-cyclopropyl appendage, but poorer activity with the 1-tert-butyl moiety. With the 1-(2,4-difluorophenyl) substitution, the influence of the 7-cycloalkylamino group was determinant: a (3S)-3-amino-pyrrolidine was shown to enhance greatly the in vitro and in vivo activity of the 5-methyl derivative. Compound 33 (BMY 43748) was selected as a promising candidate for an improved therapeutic agent.
• Structure–activity relationships of bivalent aminoglycosides and evaluation of their microbiological activities
  作者：Chang-Hsing Liang、Alex Romero、David Rabuka、Paulo W.M. Sgarbi、Kenneth A. Marby、Jonathan Duffield、Sulan Yao、Mayling L. Cheng、Yoshi Ichikawa、Pamela Sears、Changyong Hu、San-Bao Hwang、Youe-Kong Shue、Steven J. Sucheck

  DOI：10.1016/j.bmcl.2005.02.029

  日期：2005.4

  A library of 4,5- and 4,6-linked bivalent aminoglycoside (AMG) antibiotics consisting of neamine and nebramine pharmacophores have been synthesized. We probed the effect of the linker on antibiotic activity with a series of selected synthetic analogues with varied length and substituents. A number of compounds demonstrated in vitro activity against several bacterial strains and showed activity against drug resistant strains of Pseudomonas aeruginosa. Among the compounds prepared, analogues 12a-d were novel 4,6-linked AMGs containing the nebramine pharmacophore. In addition the lead compound OPT-11 possessed an ED50 of <= 5 mg/kg in a Staphylococcus aureus ATCC 29213 mouse protection model. (c) 2005 Elsevier Ltd. All rights reserved.