(S)-2-[(R)-7-(3,5-dichlorophenyl)-5-methyl-6-oxo-5-(4-trifluoromethoxybenzyl)-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-sulfonylamino]propionamide | 688756-00-5

• 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-[(R)-7-(3,5-dichlorophenyl)-5-methyl-6-oxo-5-(4-trifluoromethoxybenzyl)-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-sulfonylamino]propionamide
• 英文别名: (S)-2-[(R)-7-(3,5-dichlorophenyl)-5-methyl-6-oxo-5-(4-trifluoromethoxybenzyl)-6,7-dihydro-5H-imidazo[1,2-a]imidazol-3-ylsulfonylamino]propionamide；(2S)-2-[[(5R)-7-(3,5-dichlorophenyl)-5-methyl-6-oxo-5-[[4-(trifluoromethoxy)phenyl]methyl]imidazo[1,2-a]imidazol-3-yl]sulfonylamino]propanamide；BIRT2584；(S)-2-[(R)-7-(3,5-dichloro-phenyl)-5-methyI-6-oxo-5-(4-trifluoromethoxy-benzyl)-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-sulfonylamino]-propionamide；Unii-24P4O1J71F
• CAS: 688756-00-5
• 化学式: C₂₃H₂₀Cl₂F₃N₅O₅S
• 分子量: 606.41
• InChiKey: QSNSVPRLHYSSQG-AMXDTQDGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  39
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  145
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  (S)-2-[(R)-7-(3,5-dichloro-phenyl)-5-methyI-6-oxo-5-(4-trifluoromethoxy-benzyl)-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-sulfonylamino]-N-(2-hydroxy-2-methyl-propyl)-propionamide 、 (S)-2-[(R)-7-(3,5-dichlorophenyl)-5-methyl-6-oxo-5-(4-trifluoromethoxybenzyl)-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-sulfonylamino]propionamide 、 (S)-N-carbamoylmethyl-2-[(R)-5-(4-cyano-benzyl)-7-(3,5-dichloro-phenyl)-5-methyI-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-sulfonylamino]-propionamide 生成 (S)-2-[(R)-5-(4-cyano-benzyI)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a] imidazole-3-sulfonylamino]-propionamide
  参考文献：
  名称：

  Derivatives of [6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-sulfonylamino]-propionamide

  摘要：

  [6,7-二氢-5H-咪唑[1,2-a]咪唑-3-磺酰胺]-丙酰胺的衍生物，对CAMs和Leukointegrins的相互作用表现出良好的抑制作用，因此在治疗炎症性疾病方面非常有用。

  公开号：

  US20050054703A1
• 作为产物：
  描述：

  (R)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-5-(4-trifluoromethoxy-benzyl)-6,7-dihydro-5H-imidazo[1, 2-a]imidazole-3-sulfonyl chloride 、 L-丙氨酰胺盐酸盐 在 三乙胺 作用下， 以 DMF (N,N-dimethyl-formamide) 、 二氯甲烷 为溶剂， 反应 5.0h， 以81%的产率得到(S)-2-[(R)-7-(3,5-dichlorophenyl)-5-methyl-6-oxo-5-(4-trifluoromethoxybenzyl)-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-sulfonylamino]propionamide
  参考文献：
  名称：

  [EN] DERIVATIVES OF [6,7-DIHYDRO-5H-IMIDAZO[1,2-alpha] IMIDAZOLE-3-SULFONYLAMINO]-PROPIONAMIDE AND THEIR USE AS INHIBITORS UPON THE INTERACTION OF CAMS AND LEUKO INTEGRINS
  [FR] DERIVES DE [6,7-DIHYDRO-5H-IMIDAZO[1,2-A]IMIDAZOLE-3-SULFONYLAMINO]-PROPIONAMIDE

  摘要：

  公开号：

  WO2004041827A3

文献信息

• Synthesis of 6,7-Dihydro-5H-imidazo[1,2-a]imidazole-3-sulfonic acid amides
  申请人：WIRTH Thomas

  公开号：US20070173517A1

  公开（公告）日：2007-07-26

  Disclosed is an improved multi-step process for preparing a compound of Formula I: wherein R 1 to R 3 are as defined herein. The compounds of formula I inhibit the binding of human intercellular adhesion molecules to the Leukointegrins. As a result, these compounds are useful in the treatment of inflammatory and immune cell-mediated diseases.

  公开了一种改进的多步骤制备Formula I化合物的方法：其中R1到R3如本文所定义。 Formula I化合物抑制人类细胞间粘附分子与白细胞整合素的结合。因此，这些化合物在治疗炎症和免疫介导的细胞疾病方面是有用的。
• Asymmetric Synthesis of LFA-1 Inhibitor BIRT2584 on Metric Ton Scale
  作者：Xiao-Jun Wang、Rogelio P. Frutos、Li Zhang、Xiufeng Sun、Yibo Xu、Thomas Wirth、Thomas Nicola、Lawrence J. Nummy、Dhileep Krishnamurthy、Carl A. Busacca、Nathan Yee、Chris H. Senanayake

  DOI：10.1021/op200175t

  日期：2011.9.16

  The synthesis of LFA-1 inhibitor BIRT2584 on metric-ton scale was accomplished by means of a safe and robust process. Highlights of the process include the asymmetric synthesis of the key advanced intermediate by implementation of Seebach’s self-regeneration of stereocenters principle, and a Ph3PCl2-induced dehydration of a critical urea followed by a regioselective bromination to give the elaborated

  LFA-1抑制剂BIRT2584的合成以公吨为单位，是通过安全，可靠的方法完成的。该方法的亮点包括通过实施Seebach立体中心原理的自我再生来不对称合成关键高级中间体，以及Ph 3 PCl 2诱导的关键尿素脱水，然后进行区域选择性溴化，得到了精细的1 H-咪唑[1,2 - a ]咪唑-2-one。通过碘代咪唑的Br / Mg交换，然后在THF中添加至SO 2并随后进行氧化，可制得磺酰氯中间体。在一个单釜操作中，磺酰氯直接反应用升-在DMF / THF水溶液中使用NaOH作为碱的α-丙氨酰胺，得到BIRT2584。
• DERIVATIVES OF [6,7-DIHYDRO-5H-IMIDAZO[1,2-a]IMIDAZOLE-3-SULFONYLAMINO]-PROPIONAMIDE
  申请人：Kelly Alfred Terence

  公开号：US20080090819A1

  公开（公告）日：2008-04-17

  Derivatives of [6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-sulfonylamino]-propionamide which exhibit good inhibitory effect upon the interaction of CAMs and Leukointegrins and are thus useful in the treatment of inflammatory disease.

  [6,7-二氢-5H-咪唑[1,2-a]咪唑-3-磺酰胺]-丙酰胺的衍生物，在CAMs和Leukointegrins的相互作用上表现出良好的抑制效果，因此在治疗炎症性疾病方面是有用的。
• Derivates of [6, 7-dihydro - 5H - imidazo[1,2- alpha]imidazole-3-sulfonylamino]-propionamide and their use as inhibitors upon the interaction of CAMS and leukointegrins
  申请人：Boehringer Ingelheim Pharmaceuticals, Inc.

  公开号：EP1712553A2

  公开（公告）日：2006-10-18

  Derivatives of [6,7-dihydro-5H-imidazo[1,2α]imidazole-3-sulfonylamino]-propionamide of the formula I which exhibit good inhibitory effect upon the interaction of CAMs and Leukointegrins and are thus useful in the treatment of inflammatory disease.

  式 I 的[6,7-二氢-5H-咪唑并[1,2α]咪唑-3-磺酰氨基]丙酰胺的衍生物 对 CAMs 和白细胞介素的相互作用具有良好的抑制作用，因此可用于治疗炎症性疾病。
• Efficient Synthesis of a Small Molecule, Nonpeptide Inhibitor of LFA-1
  作者：Xiao-jun Wang、Yibo Xu、Li Zhang、Dhileepkumar Krishnamurthy、Thomas Wirth、Thomas Nicola、Chris H. Senanayake

  DOI：10.1021/ol101960x

  日期：2010.10.1

  A three-stage process for the synthesis of LFA-1 inhibitor 1 from amine 4 with an overall yield of 65% is described. The key stage involves a Ph(3)PCl(2)-induced dehydration/cyclization of urea 6 followed by a regioselective bromination to give (1)H-imidazo[1,2-a]imidazol-2-one 9. Br/Mg exchange of 9 followed by addition to SO(2) in THF and subsequent oxidation produces a sulfonyl chloride which is directly reacted with L-alaninamide using K(2)CO(3) as base in aqueous DMF/THF to give 1 in a one-pot operation. The process was implemented for the production of 1 on a metric ton scale.