1-(R)-(piperazin-1-yl)propan-2-ol | 954138-60-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 1-(R)-(piperazin-1-yl)propan-2-ol
• 英文别名: (R)-1-(piperazin-1-yl)propan-2-ol；(2R)-1-(piperazin-1-yl)propan-2-ol；(2R)-1-piperazin-1-ylpropan-2-ol
• CAS: 954138-60-4
• 化学式: C₇H₁₆N₂O
• mdl: MFCD19227724
• 分子量: 144.217
• InChiKey: XAKIZRLIXGLPBW-SSDOTTSWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  10
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  35.5
• 氢给体数：
  2
• 氢受体数：
  3

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 、 1-(R)-(piperazin-1-yl)propan-2-ol 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 生成 7-chloro-3-[4-[(2R)-2-hydroxypropyl]piperazin-1-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

文献信息

• Structure–Activity Relationships for a Series of (Bis(4-fluorophenyl)methyl)sulfinyl Alkyl Alicyclic Amines at the Dopamine Transporter: Functionalizing the Terminal Nitrogen Affects Affinity, Selectivity, and Metabolic Stability
  作者：Rachel D. Slack、Therese C. Ku、Jianjing Cao、JoLynn B. Giancola、Alessandro Bonifazi、Claus J. Loland、Alexandra Gadiano、Jenny Lam、Rana Rais、Barbara S. Slusher、Mark Coggiano、Gianluigi Tanda、Amy Hauck Newman

  DOI：10.1021/acs.jmedchem.9b01188

  日期：2020.3.12

  diastereomeric separation, as well as improvements in potency and pharmacokinetics were desirable for discovering pipeline drug candidates. Thus, a series of bis(4-fluorophenyl)methyl)sulfinyl)alkyl alicyclic amines, where the piperazine-2-propanol scaffold was modified, were designed, synthesized, and evaluated for binding affinities at DAT, as well as the serotonin transporter and σ1 receptors. Within

  非典型多巴胺转运蛋白 (DAT) 抑制剂已在精神兴奋剂滥用的临床前模型中显示出治疗潜力。在大鼠中，1-(4-(2-((双(4-氟苯基)甲基)亚磺酰基)乙基)-哌嗪-1-基)-丙-2-醇 ( 3b ) 可有效降低两者的增强作用可卡因和甲基苯丙胺，但本身没有表现出精神兴奋行为。虽然3b的进一步开发正在进行中，但非对映异构体分离以及效力和药代动力学的改进对于发现管道候选药物是可取的。因此，设计、合成了一系列双（4-氟苯基）甲基）亚磺酰基）烷基脂环胺，其中对哌嗪-2-丙醇支架进行了修饰，并评估了其在 DAT 的结合亲和力，以及血清素转运蛋白和σ1个受体。在该系列中，14a显示出比3b ( K i = 230 nM)更高的 DAT 亲和力 ( K i = 23 nM) 、人肝微粒体中的中等代谢稳定性和 hERG/DAT 亲和力比 = 28。而14a相对于运动活性增加对于载体，它明显低于可卡因产生的活
• 6-CYCLOAMINO-3-(1H-PYRROLO[2,3-b]PYRIDIN-4-YL)IMIDAZO[1,2-b]PYRIDAZINE DERIVATIVES, PREPARATION THEREOF AND THERAPEUTIC USE THEREOF
  申请人：Pacaud Christophe

  公开号：US20120010208A1

  公开（公告）日：2012-01-12

  The invention relates to 6-cycloamino-3-(1H-pyrrolo[2,3-b]pyridin-4-yl)imidazo[1,2-b]pyridazine derivatives corresponding to the general formula (I) in which R 2 represents an aryl group optionally substituted with one or more halogen atoms or C 1-6 -alkyl, C 1-6 -alkyloxy, C 1-6 -alkylthio, C 1-6 -fluoroalkyl, C 1-6 -fluoroalkyloxy and —CN groups or R 2 represents a group chosen from C 1-6 -alkyl, C 1-6 -fluoroalkyl, C 3-7 -cycloalkyl or C 3-7 -cycloalkyl-C 1-6 -alkyl groups; A represents a C 1-7 -alkylene group; B represents a C 1-7 -alkylene group; L represents either a nitrogen atom optionally substituted with an R c or R d group, or a carbon atom substituted with an R e1 group and an R d group or two R e2 groups; the carbon atoms of A and of B being optionally substituted with one or more R f groups, which may be identical to or different from one another. Preparation process and therapeutic use.

  该发明涉及与一般式（I）相对应的6-环氨基-3-(1H-吡咯并[2,3-b]吡啶-4-基)咪唑并[1,2-b]吡啶衍生物，其中R2代表一个芳基，该芳基可选择性地取代一个或多个卤原子或C1-6-烷基、C1-6-烷氧基、C1-6-烷硫基、C1-6-氟烷基、C1-6-氟烷氧基和—CN基，或者R2代表从C1-6-烷基、C1-6-氟烷基、C3-7-环烷基或C3-7-环烷基-C1-6-烷基基团中选择的一种基团；A代表一个C1-7-烷基烯基；B代表一个C1-7-烷基烯基；L代表一个氮原子，该氮原子可选择性地取代为Rc或Rd基团，或者是一个碳原子，该碳原子取代为Re1基团和Rd基团或两个Re2基团；A和B的碳原子可选择性地取代为一个或多个Rf基团，这些基团可以相同也可以不同。制备方法和治疗用途。
• Pyridine [3,4-b] Pyrazinones
  申请人：Hughes O. Robert

  公开号：US20070249615A1

  公开（公告）日：2007-10-25

  Compounds and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula I: wherein R 2 , R 6A , R 6B and R 8 are as defined in the specification. Corresponding pharmaceutical compositions, methods of treatment, synthetic methods, and intermediates are also disclosed.

  本文披露了化合物及其药用可接受的盐，其中化合物具有以下结构的Formula I：其中R2、R6A、R6B和R8如规范中定义。同时还披露了相应的药物组合物、治疗方法、合成方法和中间体。
• Small molecule BET bromodomain inhibitors and uses thereof
  申请人：ConverGene LLC

  公开号：US11028079B2

  公开（公告）日：2021-06-08

  The present invention relates to compounds that bind to and otherwise modulate the activity of bromodomain-containing proteins, to processes for preparing these compounds, to pharmaceutical compositions containing these compounds, and to methods of using these compounds for treating a wide variety of conditions and disorders.

  本发明涉及与含溴结构域蛋白质结合或以其他方式调节其活性的化合物、制备这些化合物的工艺、含有这些化合物的药物组合物，以及使用这些化合物治疗各种病症和疾病的方法。
• PYRIDIN[3,4-B]PYRAZINONES
  申请人：Pfizer Products Inc.

  公开号：EP2013208B1

  公开（公告）日：2011-06-22