4-(2-[2-((R)-2-methyl-pyrrolidin-1-yl)-ethyl]-benzofuran-5-yl)-1H-pyrazole | 460748-95-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并呋喃
• 英文名称: 4-(2-[2-((R)-2-methyl-pyrrolidin-1-yl)-ethyl]-benzofuran-5-yl)-1H-pyrazole
• 英文别名: 1H-Pyrazole, 4-(2-(2-((2R)-2-methyl-1-pyrrolidinyl)ethyl)-5-benzofuranyl)-；4-[2-[2-[(2R)-2-methylpyrrolidin-1-yl]ethyl]-1-benzofuran-5-yl]-1H-pyrazole
• CAS: 460748-95-2
• 化学式: C₁₈H₂₁N₃O
• 分子量: 295.384
• InChiKey: DATDVQKGDSNVRT-CYBMUJFWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  45.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  1-[2-(5-bromo-1-benzofuran-2-yl)ethyl]-2(R)-methylpyrrolidine 在 bis-triphenylphosphine-palladium(II) chloride 甲酸 、 sodium carbonate 作用下， 以 1,4-二氧六环 、 乙醇 、 水 为溶剂， 反应 75.17h， 生成 4-(2-[2-((R)-2-methyl-pyrrolidin-1-yl)-ethyl]-benzofuran-5-yl)-1H-pyrazole
  参考文献：
  名称：

  Novel heterocyclic-substituted benzofuran histamine H3 receptor antagonists: In vitro properties, drug-likeness, and behavioral activity

  摘要：

  Three novel heterocyclic benzofurans A-688057 (1), A-687136 (2), and A-698418 (3) were profiled for their in vitro and in vivo properties as a new series of histamine H-3 receptor antagonists. The compounds were all found to have nanomolar potency in vitro at histamine H-3 receptors, and when profiled in vivo for CNS activity, all were found active in an animal behavioral model of attention. The compound with the most benign profile versus CNS side effects was selected for greater scrutiny of its in vitro properties and overall drug-likeness. This compound, A-688057, in addition to its potent and robust efficacy in two rodent behavioral models at blood levels ranging 0.2-19 nM, possessed other favorable features, including high selectivity for H-3 receptors (H-3, K-i = 13 nM) versus off-target receptors and channels (including the hERG K+ channel, K-i > 9000 nM), low molecular weight (295), high solubility, moderate lipophilicity (logD(pH7.4) = 2.05), and good CNS penetration (blood/brain 3.4x). In vitro toxicological tests indicated low potential for phospholipidosis, genotoxicity, and CYP450 inhibition. Even though pharmacokinetic testing uncovered only moderate to poor oral bioavailability in rat (26%), dog (30%), and monkey (8%), and only moderate blood half-lives after i.v. administration (t(1/2) in rat of 2.9 h, 1.7 h in dog, 1.8 h in monkey), suggesting poor human pharmacokinetics, the data overall indicated that A-688057 has an excellent profile for use as a pharmacological tool compound. (c) 2007 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bcp.2007.02.010

文献信息

• DETERMINATION OF HISTAMINE-3 BIOACTIVITY
  申请人：Radek Richard J.

  公开号：US20080159958A1

  公开（公告）日：2008-07-03

  The invention relates to an in vivo method for determining the bioactivity of chemical compounds as histamine-3 receptor (H 3 R) ligands, and provides animal models to determine such bioactivity. The invention further relates to methods for screening therapeutic compounds demonstrating a desired property, using such methods and models described.

  这项发明涉及一种体内方法，用于确定化合物作为组胺-3受体（H3R）配体的生物活性，并提供动物模型来确定这种生物活性。该发明还涉及使用所述方法和模型筛选展示所需特性的治疗化合物的方法。
• Novel amines as histamine-3 receptor ligands and their therapeutic applications
  申请人：——

  公开号：US20020169188A1

  公开（公告）日：2002-11-14

  Compounds of formula (I) 1 or a pharmaceutically acceptable salts or prodrug thereof which are useful for the modulation of the histamine-3 receptors in mammals and which are useful for the treatment of disorders ameliorated by histamine-3 receptor ligands.

  化合物的公式(I)1或其药用可接受的盐或前药，对哺乳动物的组胺-3受体进行调节是有用的，并且对组胺-3受体配体改善的疾病的治疗是有用的。
• Amines as histamine-3 receptor ligands and their therapeutic applications
  申请人：Abbott Laboratories

  公开号：EP2258694A1

  公开（公告）日：2010-12-08

  Compounds of formula (I), or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof, which are useful for the modulation of the histamine-3 receptors in mammals and which are useful for the treatment of disorders ameliorated by histamine-3 receptor ligands.

  式(I)化合物或其药学上可接受的盐、酯、酰胺或原药，可用于调节哺乳动物体内的组胺-3 受体，并可用于治疗组胺-3 受体配体可改善的疾病。
• NOVEL AMINES AS HISTAMINE-3 RECEPTOR LIGANDS AND THEIR THERAPEUTIC APPLICATIONS
  申请人：Abbott Laboratories

  公开号：EP1370546A2

  公开（公告）日：2003-12-17
• US7538138B2
  申请人：——

  公开号：US7538138B2

  公开（公告）日：2009-05-26