4-ethyl-5-[(tetrahydro-2H-pyran-2-yloxy)methyl]thiophene-2-carboxaldehyde | 913829-16-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 英文名称: 4-ethyl-5-[(tetrahydro-2H-pyran-2-yloxy)methyl]thiophene-2-carboxaldehyde
• 英文别名: 4-Ethyl-5-[(tetrahydro-2H-pyran-2-yloxy)methyl]thiophene-2-carboxaldehyde；4-ethyl-5-(oxan-2-yloxymethyl)thiophene-2-carbaldehyde
• CAS: 913829-16-0
• 化学式: C₁₃H₁₈O₃S
• 分子量: 254.35
• InChiKey: UOKYAWPWOFDKDD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  63.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-ethyl-5-[(tetrahydro-2H-pyran-2-yloxy)methyl]thiophene-2-carboxaldehyde 在 盐酸羟胺 、 四丁基氟化铵 、 羟胺 、 1-羟基苯并三唑 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 水 、 甲苯 、 乙腈 为溶剂， 生成 {3-Ethyl-5-[5-(4-phenoxyphenyl)-1,2,4-oxadiazol-3-yl]-2-thienyl}methanol
  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-bromothiophene-2-yl)methoxy)(tert-butyl)dimethylsilane 在 1,3-bis[(diphenylphosphino)propane]dichloronickel(II) 甲醇 、 sodium tetrahydroborate 、 重铬酸吡啶 、 正丁基锂 、 四丁基氟化铵 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 乙醚 、 正己烷 、 二氯甲烷 为溶剂， 反应 5.5h， 生成 4-ethyl-5-[(tetrahydro-2H-pyran-2-yloxy)methyl]thiophene-2-carboxaldehyde
  参考文献：
  名称：

  3-AZETIDINECARBOXYLIC ACID DERIVATIVES FOR USE AS IMMUNOSUPPRESSANTS

  摘要：

  公开号：

  EP1873153B1

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。
• 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
• Discovery of CS-2100, a potent, orally active and S1P3-sparing S1P1 agonist
  作者：Tsuyoshi Nakamura、Masayoshi Asano、Yukiko Sekiguchi、Yumiko Mizuno、Kazuhiko Tamaki、Takako Kimura、Futoshi Nara、Yumi Kawase、Takaichi Shimozato、Hiromi Doi、Takashi Kagari、Wataru Tomisato、Ryotaku Inoue、Miyuki Nagasaki、Hiroshi Yuita、Keiko Oguchi-Oshima、Reina Kaneko、Nobuaki Watanabe、Yasuyuki Abe、Takahide Nishi

  DOI：10.1016/j.bmcl.2011.12.019

  日期：2012.2

  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.