2-Bromo-1-(3-fluoro-4-propan-2-yloxyphenyl)ethanone | 1158418-35-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-Bromo-1-(3-fluoro-4-propan-2-yloxyphenyl)ethanone
• 英文别名: 2-bromo-1-(3-fluoro-4-propan-2-yloxyphenyl)ethanone
• CAS: 1158418-35-9
• 化学式: C₁₁H₁₂BrFO₂
• 分子量: 275.117
• InChiKey: IAMXKBRNCZOIPN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-Bromo-1-(3-fluoro-4-propan-2-yloxyphenyl)ethanone 在 劳森试剂 、 吡啶 、 氯化亚砜 、 二甲酰氨基钠 、 四丁基氟化铵 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 氯仿 、 甲苯 、 乙腈 为溶剂， 生成 methyl 1-((4-ethyl-5-(5-(3-fluoro-4-isopropoxyphenyl)thiazol-2-yl)thiophen-2-yl)methyl)azetidine-3-carboxylate
  参考文献：
  名称：

  Synthesis and SAR of 1,3-thiazolyl thiophene and pyridine derivatives as potent, orally active and S1P3-sparing S1P1 agonists

  摘要：

  We have previously disclosed 1,2,4-oxadiazole derivative 3 as a potent S1P(3)-sparing S1P(1) agonist. Although compound 3 exhibits potent and manageable immunosuppressive efficacy in various in vivo models, recent studies have revealed that its 1,2,4-oxadiazole ring is subjected to enterobacterial decomposition. As provisions for unpredictable issues, a series of alternative compounds were synthesized on the basis of compound 3. Extensive SAR studies led to the finding of 1,3-thiazole 24c with the EC50 value of 3.4 nM for human S1P(1), and over 5800-fold selectivity against S1P(3). In rat on host versus graft reaction (HvGR), the ID50 value of 24c was determined at 0.07 mg/kg. The pharmacokinetics in rat and monkey is also reported. Compared to compound 3, 24c showed excellent stability against enterobacteria. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.03.067
• 作为产物：
  描述：

  1-(3-fluoro-4-(1-methylethoxy)phenyl)ethanone 在 PhMe₂NBr₃ 作用下， 生成 2-Bromo-1-(3-fluoro-4-propan-2-yloxyphenyl)ethanone
  参考文献：
  名称：

  Synthesis and SAR of 1,3-thiazolyl thiophene and pyridine derivatives as potent, orally active and S1P3-sparing S1P1 agonists

  摘要：

  We have previously disclosed 1,2,4-oxadiazole derivative 3 as a potent S1P(3)-sparing S1P(1) agonist. Although compound 3 exhibits potent and manageable immunosuppressive efficacy in various in vivo models, recent studies have revealed that its 1,2,4-oxadiazole ring is subjected to enterobacterial decomposition. As provisions for unpredictable issues, a series of alternative compounds were synthesized on the basis of compound 3. Extensive SAR studies led to the finding of 1,3-thiazole 24c with the EC50 value of 3.4 nM for human S1P(1), and over 5800-fold selectivity against S1P(3). In rat on host versus graft reaction (HvGR), the ID50 value of 24c was determined at 0.07 mg/kg. The pharmacokinetics in rat and monkey is also reported. Compared to compound 3, 24c showed excellent stability against enterobacteria. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.03.067

文献信息

• Synthesis and SAR of 1,3-thiazolyl thiophene and pyridine derivatives as potent, orally active and S1P3-sparing S1P1 agonists
  作者：Masayoshi Asano、Tsuyoshi Nakamura、Yukiko Sekiguchi、Yumiko Mizuno、Takahiro Yamaguchi、Kazuhiko Tamaki、Takaichi Shimozato、Hiromi Doi-Komuro、Takashi Kagari、Wataru Tomisato、Ryotaku Inoue、Hiroshi Yuita、Keiko Oguchi-Oshima、Reina Kaneko、Futoshi Nara、Yumi Kawase、Noriko Masubuchi、Shintaro Nakayama、Tetsufumi Koga、Eiko Namba、Hatsumi Nasu、Takahide Nishi

  DOI：10.1016/j.bmcl.2012.03.067

  日期：2012.5

  We have previously disclosed 1,2,4-oxadiazole derivative 3 as a potent S1P(3)-sparing S1P(1) agonist. Although compound 3 exhibits potent and manageable immunosuppressive efficacy in various in vivo models, recent studies have revealed that its 1,2,4-oxadiazole ring is subjected to enterobacterial decomposition. As provisions for unpredictable issues, a series of alternative compounds were synthesized on the basis of compound 3. Extensive SAR studies led to the finding of 1,3-thiazole 24c with the EC50 value of 3.4 nM for human S1P(1), and over 5800-fold selectivity against S1P(3). In rat on host versus graft reaction (HvGR), the ID50 value of 24c was determined at 0.07 mg/kg. The pharmacokinetics in rat and monkey is also reported. Compared to compound 3, 24c showed excellent stability against enterobacteria. (C) 2012 Elsevier Ltd. All rights reserved.