(S)-4-(2-((4-(4-氯苯氧基)苯氧基)甲基)吡咯烷-1-基)丁酸 | 929916-05-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: (S)-4-(2-((4-(4-氯苯氧基)苯氧基)甲基)吡咯烷-1-基)丁酸
• 英文名称: DG-051
• 英文别名: 4-[(2S)-2-[[4-(4-chlorophenoxy)phenoxy]methyl]pyrrolidin-1-ium-1-yl]butanoate
• CAS: 929916-05-2
• 化学式: C₂₁H₂₄ClNO₄
• 分子量: 389.879
• InChiKey: PVCTYSQBVIGZRU-KRWDZBQOSA-N

物化性质

• 沸点：
  551.8±40.0 °C(Predicted)
• 密度：
  1.229±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  27
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  59
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (S)-4-(2-((4-(4-氯苯氧基)苯氧基)甲基)吡咯烷-1-基)丁酸 在 盐酸 作用下， 以 乙醚 为溶剂， 反应 2.0h， 生成 4-((S)-2-((4-(4-氯苯氧基)苯氧基)甲基)吡咯烷-1-基)丁酸盐酸盐
  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：

  ethyl 4-{(2S)-2-[4-(4-chlorophenoxy)phenoxymethyl]pyrrolidin-1-yl}butyrate 在 水 、 sodium hydroxide 、 盐酸 作用下， 以 甲醇 、 水 为溶剂， 反应 16.0h， 以81.3%的产率得到(S)-4-(2-((4-(4-氯苯氧基)苯氧基)甲基)吡咯烷-1-基)丁酸
  参考文献：
  名称：

  Development of a Scalable Synthetic Process for DG-051B, A First-in-Class Inhibitior of LTA4H

  摘要：

  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.

  DOI：

  10.1021/op900231j

文献信息

• Treatment of Pulmonary Hypertension with Leukotriene Inhibitors
  申请人：THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY

  公开号：US20130251787A1

  公开（公告）日：2013-09-26

  Pulmonary arterial hypertension (PAH) can be prevented in persons susceptible to the diseases and PAH patients can be treated by administering an effective dose of a leukotriene inhibitor. Suitable inhibitors include leukotriene A 4 hydrolase (LTA 4 H) inhibitors, leukotriene B 4 receptor (BLT1/BLT2) antagonists, 5-lipoxygenase (5-LO) inhibitors, and 5-lipoxgygenase activating protein (FLAP) inhibitors.

  肺动脉高压（PAH）可以在易患该病的人群中预防，并且可以通过给予有效剂量的白细胞三烯抑制剂来治疗PAH患者。合适的抑制剂包括白细胞三烯A4水解酶（LTA4H）抑制剂、白细胞三烯B4受体（BLT1/BLT2）拮抗剂、5-脂氧合酶（5-LO）抑制剂和5-脂氧合酶激活蛋白（FLAP）抑制剂。
• [EN] PROCESS FOR PREPARING 4- { (S) -2- (4-(4-CHLOROPHENOXY) PHENOXYMETHYL) PYRROLIDIN-1-YL) } BUTYRIC ACID AND SALTS THEREOF<br/>[FR] PROCÉDÉ DE PRÉPARATION DE L'ACIDE 4-{(S)-2-(4-(4-CHLOROPHÉNOXY)PHÉNOXYMÉTHYL)PYRROLIDIN-1-YL}BUTYRIQUE ET DE SES SELS
  申请人：DECODE GENETICS EHF

  公开号：WO2011011598A1

  公开（公告）日：2011-01-27

  The present invention relates to a process for preparing 4-(S)-2-[4-(4-chlorophenoxy)phenoxymethyl]pyrrolidin-1-yl}butyric acid and its salts.

  本发明涉及一种制备4-(S)-2-[4-(4-氯苯氧基)苯氧甲基]吡咯烷-1-基}丁酸及其盐的方法。
• 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
• 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.
• LTB4 INHIBITION TO PREVENT AND TREAT HUMAN LYMPHEDEMA
  申请人：The Board of Trustees of The Leland Stanford Junior University

  公开号：EP3268085A1

  公开（公告）日：2018-01-17