乙基4-(6-氯-3-吡啶基)-4-氧代丁酸酯 | 890100-63-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 酮酸及其衍生物
• 中文名称: 乙基4-(6-氯-3-吡啶基)-4-氧代丁酸酯
• 英文名称: ethyl 4-(6-chloropyridin-3-yl)-4-oxo-butyrate
• 英文别名: 4-(6-chloropyridin-3-yl)-4-oxobutyric acid ethyl ester；Ethyl 4-(6-chloropyridin-3-YL)-4-oxobutyrate；ethyl 4-(6-chloropyridin-3-yl)-4-oxobutanoate
• CAS: 890100-63-7
• 化学式: C₁₁H₁₂ClNO₃
• 分子量: 241.674
• InChiKey: JLOMUGLRAOGWJH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  16
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  56.3
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 海关编码：
  2933399090

反应信息

• 作为反应物：
  描述：

  乙基4-(6-氯-3-吡啶基)-4-氧代丁酸酯 在 盐酸 、 potassium tert-butylate 、 一水合肼 作用下， 以 1,4-二氧六环 、 乙醇 、 二甲基亚砜 为溶剂， 生成 6-[6-(Piperidin-4-yloxy)-pyridin-3-yl]-2H-pyridazin-3-one
  参考文献：
  名称：

  4-Phenoxypiperidine pyridazin-3-one histamine H3 receptor inverse agonists demonstrating potent and robust wake promoting activity

  摘要：

  Structure-activity relationships for a series of phenoxypiperidine pyridazin-3-one H3R antagonists/inverse agonists are disclosed. The search for compounds with improved hERG and DAT selectivity without the formation of in vivo active metabolites identified 6-[4-(1-cyclobutyl-piperidin-4-yloxy)phenyl]- 4,4-dimethyl-4,5-dihydro-2H-pyridazin-3-one 17b. Compound 17b met discovery flow criteria, demonstrated potent H3R functional antagonism in vivo in the rat dipsogenia model and potent wake activity in the rat EEG/EMG model at doses as low as 0.1 mg/kg ip. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.01.026
• 作为产物：
  描述：

  6-氯吡啶-3-羰酰氯 、 β-(Iodzinkio)propionsaeureethylester 在 二氯(1,10-亚铁试剂)钯(II) 作用下， 以 乙腈 为溶剂， 反应 2.0h， 以83%的产率得到乙基4-(6-氯-3-吡啶基)-4-氧代丁酸酯
  参考文献：
  名称：

  Pd催化吡啶羧酸氯化物与烷基锌试剂的交叉偶联反应

  摘要：

  报道了在 Pd(phen)Cl 2 存在下从吡啶羧酸氯化物和烷基锌试剂提供酮的有效交叉偶联反应。在氯烟酰氯的情况下，没有形成 2-氯嗪部分的 Negishi 交叉偶联产物。催化剂负载量可降低至 0.01 mol%。

  DOI：

  10.1055/s-0028-1088113

文献信息

• Substituted Pyridazinone Derivatives as Histamine-3 (H3) Receptor Ligands
  申请人：Becknell Nadine C.

  公开号：US20110098269A1

  公开（公告）日：2011-04-28

  The present invention provides compounds according to Formulas I, II, III, IV, V, VI, VII or VIII: their use as H 3 antagonists/inverse agonists, processes for their preparation, and pharmaceutical compositions thereof.

  本发明提供了公式I、II、III、IV、V、VI、VII或VIII的化合物：它们作为H3拮抗剂/逆激动剂的用途、它们的制备方法以及它们的药物组成物。
• [EN] SUBSTITUTED PYRIDAZINONE DERIVATIVES AS HISTAMINE-3 (H3) RECEPTOR LIGANDS<br/>[FR] DÉRIVÉS PYRIDAZINONE SUBSTITUÉS COMME LIGANDS DES RÉCEPTEURS DE L'HISTAMINE-3 (H3)
  申请人：CEPHALON INC

  公开号：WO2009142732A3

  公开（公告）日：2010-10-28
• Identification of pyridazin-3-one derivatives as potent, selective histamine H3 receptor inverse agonists with robust wake activity
  作者：Robert L. Hudkins、Lisa D. Aimone、Thomas R. Bailey、Robert J. Bendesky、Reddeppa reddy Dandu、Derek Dunn、John A. Gruner、Kurt A. Josef、Yin-Guo Lin、Jacquelyn Lyons、Val R. Marcy、Joanne R. Mathiasen、Babu G. Sundar、Ming Tao、Allison L. Zulli、Rita Raddatz、Edward R. Bacon

  DOI：10.1016/j.bmcl.2011.06.108

  日期：2011.9

  H3R structure-activity relationships on a novel class of pyridazin-3-one H3R antagonists/inverse agonists are disclosed. Modifications of the pyridazinone core, central phenyl ring and linker led to the identification of molecules with excellent target potency, selectivity and pharmacokinetic properties. Compounds 13 and 21 displayed potent functional H3R antagonism in vivo in the rat dipsogenia model and demonstrated robust wake activity in the rat EEG/EMG model. (C) 2011 Elsevier Ltd. All rights reserved.
• 4-Phenoxypiperidine pyridazin-3-one histamine H3 receptor inverse agonists demonstrating potent and robust wake promoting activity
  作者：Robert L. Hudkins、Allison L. Zulli、Reddeppa reddy Dandu、Ming Tao、Kurt A. Josef、Lisa D. Aimone、R. Curtis Haltiwanger、Zeqi Huang、Jacquelyn A. Lyons、Joanne R. Mathiasen、Rita Raddatz、John A. Gruner

  DOI：10.1016/j.bmcl.2012.01.026

  日期：2012.2

  Structure-activity relationships for a series of phenoxypiperidine pyridazin-3-one H3R antagonists/inverse agonists are disclosed. The search for compounds with improved hERG and DAT selectivity without the formation of in vivo active metabolites identified 6-[4-(1-cyclobutyl-piperidin-4-yloxy)phenyl]- 4,4-dimethyl-4,5-dihydro-2H-pyridazin-3-one 17b. Compound 17b met discovery flow criteria, demonstrated potent H3R functional antagonism in vivo in the rat dipsogenia model and potent wake activity in the rat EEG/EMG model at doses as low as 0.1 mg/kg ip. (C) 2012 Elsevier Ltd. All rights reserved.
• Pd-Catalyzed Cross-Coupling Reactions of Pyridine Carboxylic Acid Chlorides with Alkylzinc Reagents
  作者：Toshiyuki Iwai、Toshinobu Ohno、Takeo Nakai、Masatoshi Mihara、Takatoshi Ito、Takumi Mizuno

  DOI：10.1055/s-0028-1088113

  日期：2009.4

  The efficient cross-coupling reaction to afford ketones from pyridine carboxylic acid chlorides and alkylzinc reagents in the presence of Pd(phen)Cl 2 is reported. In the case of chloronicotinoyl chlorides, none ofNegishi cross-coupling products of 2-chloroazine moiety was formed. The catalyst loading could be reduced up to 0.01 mol%.

  报道了在 Pd(phen)Cl 2 存在下从吡啶羧酸氯化物和烷基锌试剂提供酮的有效交叉偶联反应。在氯烟酰氯的情况下，没有形成 2-氯嗪部分的 Negishi 交叉偶联产物。催化剂负载量可降低至 0.01 mol%。