(4-cyclobutyl-1,4-diazepan-1-yl)[6-(4-fluorophenoxy)pyridin-3-yl]methanone | 959740-39-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (4-cyclobutyl-1,4-diazepan-1-yl)[6-(4-fluorophenoxy)pyridin-3-yl]methanone
• 英文别名: JNJ-39220675；(4-Cyclobutyl-1,4-diazepan-1-yl)(6-(4-fluorophenoxy)pyridin-3-yl)methanone；(4-cyclobutyl-1,4-diazepan-1-yl)-[6-(4-fluorophenoxy)pyridin-3-yl]methanone
• CAS: 959740-39-7
• 化学式: C₂₁H₂₄FN₃O₂
• 分子量: 369.439
• InChiKey: IQOWHZHNGJXGHG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  45.7
• 氢给体数：
  0
• 氢受体数：
  5

制备方法与用途

JNJ 39220675是一种高效且选择性的脑渗透性H3受体拮抗剂，其Ki值为1.4纳摩尔，pA2值为9.42（针对hH3）。

反应信息

• 作为反应物：
  描述：

  (4-cyclobutyl-1,4-diazepan-1-yl)[6-(4-fluorophenoxy)pyridin-3-yl]methanone 在 盐酸 作用下， 以 乙醚 、 乙醇 为溶剂， 反应 20.5h， 以82%的产率得到(4-cyclobutyl[1,4]diazepan-1-yl)[6-(4-fluorophenoxy)pyridin-3-yl]methanone hydrochloride
  参考文献：
  名称：

  SUBSTITUTED PYRIDYL AMIDE COMPOUNDS AS MODULATORS OF THE HISTAMINE H3 RECEPTOR

  摘要：

  某些替代吡啶酰胺化合物是组胺H3受体调节剂，可用于治疗组胺H3受体介导的疾病。

  公开号：

  US20070281923A1
• 作为产物：
  描述：

  高哌嗪 在 正己基锂 、 caesium carbonate 作用下， 以 四氢呋喃 、 1,1-二氯乙烷 、 正己烷 、 N,N-二甲基乙酰胺 为溶剂， 反应 53.7h， 生成 (4-cyclobutyl-1,4-diazepan-1-yl)[6-(4-fluorophenoxy)pyridin-3-yl]methanone
  参考文献：
  名称：

  First, Second, and Third Generation Scalable Syntheses of Two Potent H₃ Antagonists

  摘要：

  Our teams have recently completed scale-up campaigns for two structurally similar H-3 receptor antagonists. The first and second generation processes were developed for the synthesis of 107 and 125 g batches of (4-cyclobutyl-1,4-diazepan-1-yl)(6-(4-fluorophenoxy)pyridin-3-yl)methanone center dot HCl (1 center dot HCl). A third generation process was utilized for production of 104 g of 3-((5-(4-cyclobutyl-1,4-diazepane-1-carbonyl)pyridin-2-yl)oxy)benzonitrile center dot HCl (2 center dot HCl). The evolution from first to second generation process was driven by a desire to minimize cost of goods through employment of symmetrical homopiperazine rather than a more expensive monoprotected variant. Project demands for a late stage intermediate that could provide 1 or 2 led to additional route scouting and the ultimate determination of a third scalable synthesis for these types of molecules. The use of a lithium alkoxide for Lewis base catalysis of an ester to amide transformation represents a key improvement for the third generation synthesis.

  DOI：

  10.1021/op200005e

文献信息

• PROCESS FOR THE PREPARATION OF HISTAMINE H3 RECEPTOR MODULATORS
  申请人：Broggini Diego

  公开号：US20120029189A1

  公开（公告）日：2012-02-02

  The present invention is directed to novel processes for the preparation of histamine H3 receptor modulators, in the treatment of for example, cognitive disorders, sleep disorders and/or psychiatric disorders.

  本发明涉及一种新型的组织胺H3受体调节剂制备方法，用于治疗认知障碍、睡眠障碍和/或精神障碍。
• Substituted pyridyl amide compounds as modulators of the histamine H3 receptor
  申请人：Janssen Pharmaceutica NV

  公开号：US07777031B2

  公开（公告）日：2010-08-17

  Processes are disclosed for making certain compounds of Formula (II): or their pharmaceutically active salts, that are histamine H3 receptor modulators useful in the treatment of histamine H3 receptor-mediated diseases. In one embodiment, the process comprises reacting a compound of formula (7-1): with a compound of formula (B3): in the presence of at least one equivalent of a first base, in a first organic solvent, to give a compound of Formula (II).

  揭示了制备公式（II）的某些化合物或其药物活性盐的工艺，这些化合物是组胺H3受体调节剂，可用于治疗组胺H3受体介导的疾病。在一种实施方式中，该工艺包括在第一有机溶剂中，在至少一个第一碱当量的存在下，将公式（7-1）的化合物与公式（B3）的化合物反应，以得到公式（II）的化合物。
• Process for the preparation of histamine H3 receptor modulators
  申请人：Janssen Pharmaceutica NV

  公开号：US10323002B2

  公开（公告）日：2019-06-18

  The present invention is directed to novel processes for the preparation of histamine H3 receptor modulators, in the treatment of for example, cognitive disorders, sleep disorders and/or psychiatric disorders.

  本发明涉及组胺 H3 受体调节剂的新型制备工艺，用于治疗认知障碍、睡眠障碍和/或精神障碍等疾病。
• Pre-clinical characterization of aryloxypyridine amides as histamine H3 receptor antagonists: Identification of candidates for clinical development
  作者：Michael A. Letavic、Leah Aluisio、John R. Atack、Pascal Bonaventure、Nicholas I. Carruthers、Christine Dugovic、Anita Everson、Mark A. Feinstein、Ian C. Fraser、Kenway Hoey、Xiaohui Jiang、John M. Keith、Tatiana Koudriakova、Perry Leung、Brian Lord、Timothy W. Lovenberg、Kiev S. Ly、Kirsten L. Morton、S. Timothy Motley、Diane Nepomuceno、Michele Rizzolio、Raymond Rynberg、Kia Sepassi、Jonathan Shelton

  DOI：10.1016/j.bmcl.2010.05.041

  日期：2010.7

  The pre-clinical characterization of novel aryloxypyridine amides that are histamine H-3 receptor antagonists is described. These compounds are high affinity histamine H-3 ligands that penetrate the CNS and occupy the histamine H-3 receptor in rat brain. Several compounds were extensively pro. led pre-clinically leading to the identification of two compounds suitable for nomination as development candidates. (C) 2010 Elsevier Ltd. All rights reserved.
• [EN] PROCESS FOR THE PREPARATION OF HISTAMINE H3 RECEPTOR MODULATORS<br/>[FR] PROCÉDÉ DE PRÉPARATION DE MODULATEURS DES RÉCEPTEURS D'HISTAMINE H3
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2010107897A3

  公开（公告）日：2011-04-14