(4S,7S)-16,26-bis(benzyloxy)-7-((6R,9S,12S,15S)-12-(4-methoxybenzyl)-N,2,2,6,9,11,15-heptamethyl-4,7,10,13-tetraoxo-3-oxa-5,8,11,14-tetraazahexadecan-16-amido)-5-methyl-6-oxo-5-aza-1,2(1,3)-dibenzenacyclooctaphane-4-carboxylic acid | 1374688-32-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 杂芳族化合物
• 英文名称: (4S,7S)-16,26-bis(benzyloxy)-7-((6R,9S,12S,15S)-12-(4-methoxybenzyl)-N,2,2,6,9,11,15-heptamethyl-4,7,10,13-tetraoxo-3-oxa-5,8,11,14-tetraazahexadecan-16-amido)-5-methyl-6-oxo-5-aza-1,2(1,3)-dibenzenacyclooctaphane-4-carboxylic acid
• CAS: 1374688-32-0
• 化学式: C₁₄H₂₄OSSi
• 分子量: 268.495
• InChiKey: HOZGUIBHONKBSR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  17.0
• 可旋转键数：
  4.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  9.23
• 氢给体数：
  0.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  (4S,7S)-16,26-bis(benzyloxy)-7-((6R,9S,12S,15S)-12-(4-methoxybenzyl)-N,2,2,6,9,11,15-heptamethyl-4,7,10,13-tetraoxo-3-oxa-5,8,11,14-tetraazahexadecan-16-amido)-5-methyl-6-oxo-5-aza-1,2(1,3)-dibenzenacyclooctaphane-4-carboxylic acid 在 正丁基锂 、 tris(triphenylphosphine)rhodium(l) chloride 、 四溴化碳 、 盐酸羟胺 、 四丁基氟化铵 、 氢气 、 羟胺 、 1-羟基苯并三唑 、 三乙胺 、 N,N-二异丙基乙胺 、 N,N'-二环己基碳二亚胺 、 三苯基膦 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 水 、 甲苯 、 乙腈 、 苯 为溶剂， 生成
  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-溴-2-噻吩基)甲醇 在 咪唑 、 1,3-bis[(diphenylphosphino)propane]dichloronickel(II) 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 (4S,7S)-16,26-bis(benzyloxy)-7-((6R,9S,12S,15S)-12-(4-methoxybenzyl)-N,2,2,6,9,11,15-heptamethyl-4,7,10,13-tetraoxo-3-oxa-5,8,11,14-tetraazahexadecan-16-amido)-5-methyl-6-oxo-5-aza-1,2(1,3)-dibenzenacyclooctaphane-4-carboxylic 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