3-fluoro-4-phenoxybenzoic acid | 129623-62-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-fluoro-4-phenoxybenzoic acid
• CAS: 129623-62-7
• 化学式: C₁₃H₉FO₃
• 分子量: 232.211
• InChiKey: LGDPKLNCYZIMCG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-fluoro-4-phenoxybenzoic acid 在 四溴化碳 、 四丁基氟化铵 、 1-羟基苯并三唑 、 N,N-二异丙基乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙腈 为溶剂， 生成 methyl 1-({4-ethyl-5-[5-(3-fluoro-4-phenoxyphenyl)-1,2,4-oxadiazol-3-yl]-2-thienyl}methyl)azetidine-3-carboxylate
  参考文献：
  名称：

  Discovery of CS-2100, a potent, orally active and S1P3-sparing S1P1 agonist

  摘要：

  S1P(3)-sparing S1P(1) agonists have attracted attention as a suppressant of autoimmunity with reduced side effects. Our synthetic efforts and extensive SAR studies led to the discovery of 10b named CS-2100 with the EC50 value of 4.0 nM for human S1P(1) and over 5000-fold selectivity against S1P(3). The in vivo immunosuppressive efficacy was evaluated in rats on host versus graft reaction and the ID50 value was determined at 0.407 mg/kg. The docking studies of CS-2100 with the homology model of S1P(1) and S1P(3) showed that the ethyl group on the thiophene ring of CS-2100 was sterically hindered by Phe263 in S1P(3), not in the case of Leu276 in S1P(1). This observation gives an explanation for the excellent S1P(3)-sparing characteristic of CS-2100. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.12.019
• 作为产物：
  描述：

  4-氟-3-苯氧基苯甲醛 在 sodium chlorite 、 potassium dihydrogenphosphate 、 2-甲基-2-丁烯 、 水 作用下， 以 四氢呋喃 、 叔丁醇 为溶剂， 生成 3-fluoro-4-phenoxybenzoic acid
  参考文献：
  名称：

  Discovery of CS-2100, a potent, orally active and S1P3-sparing S1P1 agonist

  摘要：

  S1P(3)-sparing S1P(1) agonists have attracted attention as a suppressant of autoimmunity with reduced side effects. Our synthetic efforts and extensive SAR studies led to the discovery of 10b named CS-2100 with the EC50 value of 4.0 nM for human S1P(1) and over 5000-fold selectivity against S1P(3). The in vivo immunosuppressive efficacy was evaluated in rats on host versus graft reaction and the ID50 value was determined at 0.407 mg/kg. The docking studies of CS-2100 with the homology model of S1P(1) and S1P(3) showed that the ethyl group on the thiophene ring of CS-2100 was sterically hindered by Phe263 in S1P(3), not in the case of Leu276 in S1P(1). This observation gives an explanation for the excellent S1P(3)-sparing characteristic of CS-2100. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.12.019

文献信息

• Heterocyclic compound
  申请人：Nishi Takahide

  公开号：US20080113961A1

  公开（公告）日：2008-05-15

  A compound having immunosuppressive activity with low toxicity or a pharmacological salt thereof. The compound has a general formula (I) shown below or a pharmacologically acceptable salt thereof, or a pharmacologically acceptable prodrug thereof

  具有低毒性免疫抑制活性的化合物或其药理盐。该化合物具有下面所示的一般式（I）或其药理学上可接受的盐，或其药理学上可接受的前体。
• HETEROCYCLIC COMPOUND
  申请人：Daiichi Sankyo Company, Limited

  公开号：EP1873153A1

  公开（公告）日：2008-01-02

  [Object] To provide a novel compound having an excellent immunosuppressive activity with low toxicity or a pharmacological salt thereof. [Means to achieve the object] A compound having general formula (I) shown below or a pharmacologically acceptable salt thereof, or a pharmacologically acceptable prodrug thereof [wherein A represents a carboxyl group, or the like, B represents a hydrogen atom, or the like, V represents a single bond, a methylene group, or the like, n represents an integer of from 0 to 2, W represents a 5- to 7-membered heterocyclic group, or the like, Z represents a group selected from Substituent group A, or the like, and Substituent group A represents the group consisting of a halogen atom, a C1-C6 alkyl group, a C3-C7 cycloalkyl group.

  目的 提供一种具有优异免疫抑制活性且毒性低的新型化合物或其药理盐。 [实现目标的方法］ 具有下图所示通式 (I) 的化合物或其药理学上可接受的盐，或其药理学上可接受的原药 其中 A代表羧基等，B代表氢原子等，V代表单键、亚甲基等，n代表0～2的整数，W代表5～7元杂环基等，Z代表选自取代基A等的基团，取代基A代表由卤素原子、C1～C6烷基、C3～C7环烷基组成的基团。
• <i>N</i>-Pyridyl and Pyrimidine Benzamides as KCNQ2/Q3 Potassium Channel Openers for the Treatment of Epilepsy
  作者：George Amato、Rosemarie Roeloffs、Greg C. Rigdon、Brett Antonio、Theresa Mersch、Grant McNaughton-Smith、Alan D. Wickenden、Paul Fritch、Mark J. Suto

  DOI：10.1021/ml200053x

  日期：2011.6.9

  A series of N-pyridyl benzamide KCNQ2/Q3 potassium channel openers were identified and found to be active in animal models of epilepsy and pain. The best compound 12 [ICA-027243, N-(6-chloro-pyridin-3-yl)-3,4-difluoro-benzamide] has an EC(50) of 0.38 mu M and is selective for KCNQ2/Q3 channels. This compound was active in several rodent models of epilepsy and pain but upon repeated dosing had a number of unacceptable toxicities that prevented further development. On the basis of the structure activity relationships developed around 12, a second compound, 51, [N-(2-chloro-pyrimidin-5-yl)-3,4-difluoro-benzamide, ICA-069673], was prepared and advanced into a phase 1 clinical study. Herein, we describe the structure activity relationships that led to the identification of compound 12 and to the corresponding pyrimidine 51.
• 3-AZETIDINECARBOXYLIC ACID DERIVATIVES FOR USE AS IMMUNOSUPPRESSANTS
  申请人：Daiichi Sankyo Company, Limited

  公开号：EP1873153B1

  公开（公告）日：2010-07-07
• US7687491B2
  申请人：——

  公开号：US7687491B2

  公开（公告）日：2010-03-30