(S)-2-amino-3-benzyloxy-N-(4-(cyclohexyloxy)phenyl)propanamide | 1222196-43-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (S)-2-amino-3-benzyloxy-N-(4-(cyclohexyloxy)phenyl)propanamide
• 英文别名: (S)-2-amino-3-(benzyloxy)-N-(4-(cyclohexyloxy)phenyl)propanamide；(2S)-2-amino-N-(4-cyclohexyloxyphenyl)-3-phenylmethoxypropanamide
• CAS: 1222196-43-1
• 化学式: C₂₂H₂₈N₂O₃
• 分子量: 368.476
• InChiKey: BDHOMQIUVZIFFC-NRFANRHFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  27
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  73.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-2-amino-3-benzyloxy-N-(4-(cyclohexyloxy)phenyl)propanamide 、 咪唑-4-乙酸 在 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (S)-2-(2-(1H-imidazol-5-yl)acetamido)-3-(benzyloxy)-N-(4-(cyclohexyloxy)phenyl)propanamide
  参考文献：
  名称：

  Discovery of a Novel Class of Potent and Orally Bioavailable Sphingosine 1-Phosphate Receptor 1 Antagonists

  摘要：

  A series of subtype selective sphingosine 1-phosphate receptor 1 (S1P(1)) antagonists are disclosed. Our high-throughput screening campaign revealed hit 1 for which an increase in potency and mouse oral exposure was achieved with minor modifications to the chemical scaffold. In vivo efficacy revealed that at high doses compounds 12 and 15 inhibited tumor growth. Further optimization of our lead series led to the discovery of proline derivatives 37 (XL541) and 38 which had similar efficacy as our first generation analogues at significantly lower doses. Analogue 37 displayed excellent pharmacokinetics and oral exposure in multiple species.

  DOI：

  10.1021/jm201533b
• 作为产物：
  描述：

  4- 环己基醚-苯胺 在 盐酸 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 生成 (S)-2-amino-3-benzyloxy-N-(4-(cyclohexyloxy)phenyl)propanamide
  参考文献：
  名称：

  Discovery of a Novel Class of Potent and Orally Bioavailable Sphingosine 1-Phosphate Receptor 1 Antagonists

  摘要：

  A series of subtype selective sphingosine 1-phosphate receptor 1 (S1P(1)) antagonists are disclosed. Our high-throughput screening campaign revealed hit 1 for which an increase in potency and mouse oral exposure was achieved with minor modifications to the chemical scaffold. In vivo efficacy revealed that at high doses compounds 12 and 15 inhibited tumor growth. Further optimization of our lead series led to the discovery of proline derivatives 37 (XL541) and 38 which had similar efficacy as our first generation analogues at significantly lower doses. Analogue 37 displayed excellent pharmacokinetics and oral exposure in multiple species.

  DOI：

  10.1021/jm201533b

文献信息

• Sphingosine-1-Phosphate Receptor Antagonists
  申请人：Ibrahim Mohamed Abdulkader

  公开号：US20110288076A1

  公开（公告）日：2011-11-24

  This disclosure relates to sphingosine-1-phosphate (S1P) receptor antagonists, compositions comprising the S1P receptor antagonists and methods for using and processes for making the S1P receptor antagonists. In particularly, this disclosure relates to sphingosine-1-phosphate 1 (S1P1) receptor antagonists, compositions comprising the S1P1 receptor antagonist and methods for using the S1P1 receptor antagonist, such as in the treatment of cancer, and processes for making the S1P1 receptor antagonists.

  本公开涉及鞘氨醇-1-磷酸（S1P）受体拮抗剂，包括含有S1P受体拮抗剂的组合物，以及使用和制备S1P受体拮抗剂的方法。特别地，本公开涉及鞘氨醇-1-磷酸1（S1P1）受体拮抗剂，包括含有S1P1受体拮抗剂的组合物，以及使用S1P1受体拮抗剂的方法，例如用于治疗癌症，以及制备S1P1受体拮抗剂的方法。
• Acetanilide sphingosine-1-phosphate receptor antagonists
  申请人：Ibrahim Mohamed Abdulkader

  公开号：US08791102B2

  公开（公告）日：2014-07-29

  This disclosure relates to sphingosine-1-phosphate (S1P) receptor antagonists, compositions comprising the S1P receptor antagonists and methods for using and processes for making the S1P receptor antagonists. In particular, this disclosure relates to sphingosine-1-phosphate 1 (S1P1) receptor antagonists, compositions comprising the S1P1 receptor antagonist and methods for using the S1P1 receptor antagonist, such as in the treatment of cancer, and processes for making the S1P1 receptor antagonists.

  本披露涉及鞘氨醇-1-磷酸（S1P）受体拮抗剂，包括含有S1P受体拮抗剂的组合物以及使用S1P受体拮抗剂的方法和制备S1P受体拮抗剂的过程。特别是，本披露涉及鞘氨醇-1-磷酸1（S1P1）受体拮抗剂，包括含有S1P1受体拮抗剂的组合物以及使用S1P1受体拮抗剂的方法，例如用于癌症治疗，并制备S1P1受体拮抗剂的过程。
• US8791102B2
  申请人：——

  公开号：US8791102B2

  公开（公告）日：2014-07-29
• Discovery of a Novel Class of Potent and Orally Bioavailable Sphingosine 1-Phosphate Receptor 1 Antagonists
  作者：Mohamed A. Ibrahim、Henry W. B. Johnson、Joon Won Jeong、Gary L. Lewis、Xian Shi、Robin T. Noguchi、Matthew Williams、James W. Leahy、John M. Nuss、John Woolfrey、Monica Banica、Frauke Bentzien、Yu-Chien Chou、Anna Gibson、Nathan Heald、Peter Lamb、Larry Mattheakis、David Matthews、Aaron Shipway、Xiang Wu、WenTao Zhang、Sihong Zhou、Geetha Shankar

  DOI：10.1021/jm201533b

  日期：2012.2.9

  A series of subtype selective sphingosine 1-phosphate receptor 1 (S1P(1)) antagonists are disclosed. Our high-throughput screening campaign revealed hit 1 for which an increase in potency and mouse oral exposure was achieved with minor modifications to the chemical scaffold. In vivo efficacy revealed that at high doses compounds 12 and 15 inhibited tumor growth. Further optimization of our lead series led to the discovery of proline derivatives 37 (XL541) and 38 which had similar efficacy as our first generation analogues at significantly lower doses. Analogue 37 displayed excellent pharmacokinetics and oral exposure in multiple species.