tert-butyl (2S)-2-[(4-iodophenoxy)methyl]pyrrolidine-1-carboxylate | 1198149-98-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: tert-butyl (2S)-2-[(4-iodophenoxy)methyl]pyrrolidine-1-carboxylate
• 英文别名: (S)-2-(4-iodo-phenoxymethyl)-pyrrolidine-1-carboxylic acid tert-butyl ester
• CAS: 1198149-98-2
• 化学式: C₁₆H₂₂INO₃
• 分子量: 403.26
• InChiKey: RNAWRGHQADWRPO-ZDUSSCGKSA-N

物化性质

• 熔点：
  90.8 °C
• 沸点：
  434.5±20.0 °C(Predicted)
• 密度：
  1.448±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl (2S)-2-[(4-iodophenoxy)methyl]pyrrolidine-1-carboxylate 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 16.0h， 以85%的产率得到(S)-2-[4-(4-iodo-benzyl)-phenoxymethyl]-pyrrolidine hydrochloride
  参考文献：
  名称：

  BIARYL SUBSTITUTED HETEROCYCLE INHIBITORS OF LTA4H FOR TREATING INFLAMMATION

  摘要：

  这项发明涉及一种化学类别的双芳基取代杂环抑制剂，用于治疗、预防和预防炎症性疾病和紊乱。这些化合物具有一般公式Ψ：一个例子是

  公开号：

  US20070066820A1
• 作为产物：
  描述：

  4-碘苯酚 、 (S)-2-(甲苯磺酰氧基甲基)吡咯烷-1-甲酸叔丁酯 在 potassium tert-butylate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 20.0h， 以92%的产率得到tert-butyl (2S)-2-[(4-iodophenoxy)methyl]pyrrolidine-1-carboxylate
  参考文献：
  名称：

  LTA4H抑制剂DG-051的两种主要代谢产物的合成和结构分配

  摘要：

  在大鼠，狗，猴和人肝微粒体的存在下，产生了相同的两种主要的CYP介导的DG-051代谢产物。根据与母体结构相关的质谱数据假设其各自的结构，并通过与真实的合成样品进行比较进行确认。使用选择性氘化的DG-051类似物的代谢研究，可以缩小合成为代谢物M1候选物的区域异构体的数量。

  DOI：

  10.1016/j.bmcl.2009.09.097

文献信息

• Biaryl substituted heterocycle inhibitors of LTA4H for treating inflammation
  申请人：deCODE genectics ehf.

  公开号：US07402684B2

  公开（公告）日：2008-07-22

  The present invention relates to a chemical genus of biaryl substituted heterocycle inhibitors of LTA4H (leukotriene A4 hydrolase) useful for the treatment and prevention and prophylaxis of inflammatory diseases and disorders. The compounds have general formula Ψ: An example is

  本发明涉及一种化学种类的双芳基取代杂环抑制剂LTA4H（白三烯A4水解酶），可用于治疗、预防和预防炎症性疾病和疾病。该化合物具有一般式Ψ：一个例子是
• Development of a Scalable Synthetic Process for DG-051B, A First-in-Class Inhibitior of LTA4H
  作者：Livia A. Enache、Isaac Kennedy、David W. Sullins、Wei Chen、Dragan Ristic、Glenn L. Stahl、Sergey Dzekhtser、Robert A. Erickson、Changren Yan、Frank W. Muellner、Michael D. Krohn、Jennifer Winger、Vincent Sandanayaka、Jasbir Singh、David E. Zembower、Alex S. Kiselyov

  DOI：10.1021/op900231j

  日期：2009.11.20

  DG-051B is a first-in-class small molecule inhibitor of leukotriene A4 hydrolase (LTA4H), currently in Phase H clinical development for the prevention of heart attack. Process optimization led from a linear seven-step synthetic procedure to a convergent four-step manufacturing sequence that has been used to manufacture at 100-kg scale. The entire process can be telescoped due to high conversion reactions, low impurity levels, efficient separations, and a very effective final purification. Two key aspects of the process are: (a) bypassing the isolation of a reactive electrophile by using its aqueous-washed reaction mixture directly into a coupling reaction with a phenoxide nucleophile and (b) modulating the properties of the final product solutions for optimal extraction, purification, and crystallization.
• Discovery of 4-[(2<i>S</i>)-2-{[4-(4-Chlorophenoxy)phenoxy]methyl}-1-pyrrolidinyl]butanoic Acid (DG-051) as a Novel Leukotriene A4 Hydrolase Inhibitor of Leukotriene B4 Biosynthesis
  作者：Vincent Sandanayaka、Bjorn Mamat、Rama K. Mishra、Jennifer Winger、Michael Krohn、Li-Ming Zhou、Monica Keyvan、Livia Enache、David Sullins、Emmanuel Onua、Jun Zhang、Gudrun Halldorsdottir、Heida Sigthorsdottir、Audur Thorlaksdottir、Gudmundur Sigthorsson、Margret Thorsteinnsdottir、Douglas R. Davies、Lance J. Stewart、David E. Zembower、Thorkell Andresson、Alex S. Kiselyov、Jasbir Singh、Mark E. Gurney

  DOI：10.1021/jm900838g

  日期：2010.1.28

  Both in-house human genetic and literature data have converged on the identification of leukotriene 4 hydrolase (LTA(4)H) as a key target for the treatment of cardiovascular disease. We combined fragment-based crystallography screening with an iterative medicinal chemistry effort to optimize inhibitors of LTA(4)H. Ligand efficiency was followed throughout our structure-activity studies. As applied within the context of LTA(4)H inhibitor design, the chemistry team was able to design a potent compound 20 (DG-051) (K(d) = 26 nM) with high aqueous solubility (>30 mg/mL) and high oral bioavailability (>80% across species) that is currently undergoing clinical evaluation for the treatment of myocardial infarction and stroke. The structural biology-chemistry interaction described in this paper provides a sound alternative to conventional screening techniques. This is the first example of a gene-to-clinic paradigm enabled by a fragment-based drug discovery effort.
• US7402684B2
  申请人：——

  公开号：US7402684B2

  公开（公告）日：2008-07-22
• US8598359B2
  申请人：——

  公开号：US8598359B2

  公开（公告）日：2013-12-03