6-(difluoromethoxy)-4-methylnicotinaldehyde | 1079352-17-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 6-(difluoromethoxy)-4-methylnicotinaldehyde
• 英文别名: 6-(Difluoromethoxy)-4-methylnicotinaldehyde；6-(difluoromethoxy)-4-methylpyridine-3-carbaldehyde
• CAS: 1079352-17-2
• 化学式: C₈H₇F₂NO₂
• 分子量: 187.146
• InChiKey: JCBACWHNOHQESA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  39.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-(difluoromethoxy)-4-methylnicotinaldehyde 、 3-(1-ethylpropyl)-5-methyl-1H-pyrrole-2-caboxylic acid ethylamide 在 氧气 作用下， 以 5,5-dimethyl-1,3-cyclohexadiene 为溶剂， 反应 10.0h， 生成 2-[6-(difluoromethoxy)-4-methyl-3-pyridinyl]-3,7-dimethyl-5-(3-pentanyl)pyrrolo[2,1-f][1,2,4]triazin-4(3H)-one
  参考文献：
  名称：

  Pyrrolo[1,2-b]pyridazines, pyrrolo[2,1-f]triazin-4(3H)-ones, and related compounds as novel corticotropin-releasing factor 1 (CRF1) receptor antagonists

  摘要：

  To identify structurally novel corticotropin-releasing factor 1 (CRF1) receptor antagonists, a series of bicyclic core analogs pyrrolo[1,2-b]pyridazines and pyrrolo[2,1-f]triazin-4(3H)-ones, which were designed based on a monocyclic core antagonist, was synthesized and evaluated. Among the compounds tested, 2-difluoromethoxy-4-methylpyridin-5-yl analog 27 was found to show efficacy in a dose-dependent manner in an elevated plus maze test in rats. The discovery process and structure-activity relationship is presented. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.11.015
• 作为产物：
  描述：

  Ethyl 6-(difluoromethoxy)-4-methylnicotinate 在 lithium aluminium tetrahydride 、 4-(1-ethylpropyl)-2-methyl-1H-pyrrole 、 sodium hydroxide 、 三氧化硫吡啶 、 三乙胺 作用下， 以 四氢呋喃 、 二甲基亚砜 为溶剂， 反应 0.25h， 生成 6-(difluoromethoxy)-4-methylnicotinaldehyde
  参考文献：
  名称：

  EP2154139

  摘要：

  公开号：

文献信息

• BICYCLIC HETEROCYCLIC COMPOUND
  申请人：Saito Tetsuji

  公开号：US20100137318A1

  公开（公告）日：2010-06-03

  A compound of a formula (I): wherein R 1 represents a C3-10 branched alkyl group which may be substituted; R 2 represents a hydrogen atom or a C1-4 alkyl group which may be substituted; R 3 represents a C1-4 alkyl group which may be substituted or a halogen atom; R 4 represents a C1-4 alkyl group which may be substituted; and ring 1 represents a cyclic group which has planarity and may have a substituent group, a salt thereof, an N-oxide thereof or a solvate thereof, or a prodrug thereof, is useful as a medicinal component having CRF antagonistic activity for the prevention and/or treatment of a neuropsychiatric disease, a peripheral organ disease and the like.

  化合物的化学式（I）：其中R1代表一个C3-10支链烷基，可以被取代; R2代表氢原子或C1-4烷基，可以被取代; R3代表C1-4烷基，可以被取代或卤素原子; R4代表C1-4烷基，可以被取代; 环1表示具有平面性且可能具有取代基团的环状基团，其盐，其N-氧化物或其溶剂化物，或其前药，可用作具有CRF拮抗活性的药物成分，用于预防和/或治疗神经精神疾病，外周器官疾病等。
• US8420810B2
  申请人：——

  公开号：US8420810B2

  公开（公告）日：2013-04-16
• EP2154139
  申请人：——

  公开号：——

  公开（公告）日：——
• Pyrrolo[1,2-b]pyridazines, pyrrolo[2,1-f]triazin-4(3H)-ones, and related compounds as novel corticotropin-releasing factor 1 (CRF1) receptor antagonists
  作者：Tetsuji Saito、Tetsuo Obitsu、Hiroshi Kohno、Isamu Sugimoto、Takeshi Matsushita、Taihei Nishiyama、Tomoko Hirota、Hiroyuki Takeda、Naoya Matsumura、Sonoko Ueno、Akihiro Kishi、Yoshifumi Kagamiishi、Hisao Nakai、Yoshikazu Takaoka

  DOI：10.1016/j.bmc.2011.11.015

  日期：2012.1

  To identify structurally novel corticotropin-releasing factor 1 (CRF1) receptor antagonists, a series of bicyclic core analogs pyrrolo[1,2-b]pyridazines and pyrrolo[2,1-f]triazin-4(3H)-ones, which were designed based on a monocyclic core antagonist, was synthesized and evaluated. Among the compounds tested, 2-difluoromethoxy-4-methylpyridin-5-yl analog 27 was found to show efficacy in a dose-dependent manner in an elevated plus maze test in rats. The discovery process and structure-activity relationship is presented. (C) 2011 Elsevier Ltd. All rights reserved.