2-((cyanomethyl)(3,4-dichlorophenyl)amino)acetic acid | 1003878-21-4

• 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: 2-((cyanomethyl)(3,4-dichlorophenyl)amino)acetic acid
• 英文别名: N-(cyanomethyl)-N-(3,4-dichlorophenyl)glycine；2-[3,4-dichloro-N-(cyanomethyl)anilino]acetic acid
• CAS: 1003878-21-4
• 化学式: C₁₀H₈Cl₂N₂O₂
• 分子量: 259.092
• InChiKey: CRTHGUJMSHCKNT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  64.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(4-溴苯基)-N-甲基-2-(吡咯烷-1-基)乙烷-1-胺 、 2-((cyanomethyl)(3,4-dichlorophenyl)amino)acetic acid 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 N-[1-(4-bromophenyl)-2-pyrrolidin-1-ylethyl]-2-[3,4-dichloro-N-(cyanomethyl)anilino]-N-methylacetamide
  参考文献：
  名称：

  Potent and selective small-molecule human urotensin-II antagonists with improved pharmacokinetic profiles

  摘要：

  Lead compound 1 was successfully redesigned to provide compounds with improved pharmacokinetic profiles for this series of human urotensin-II antagonists. Replacement of the 2-pyrrolidinylmethyl-3-phenyl-piperidine core of 1 with a substituted N-methyl-2-(1-pyrrolidinyl) ethanamine core as in compound 7 resulted in compounds with improved oral bioavailability in rats. The relationship between stereochemistry and selectivity for hUT over the kappa-opioid receptor was also explored. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.05.058
• 作为产物：
  描述：

  N-3,4-dichlorophenyl glycine ethyl ester 在 N-甲基吡咯烷酮 、 N,N-二异丙基乙胺 、 sodium iodide 、 lithium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 17.0h， 生成 2-((cyanomethyl)(3,4-dichlorophenyl)amino)acetic acid
  参考文献：
  名称：

  3,4-다이클로로페닐기를 포함하는 아세트아마이드 유도체 또는 이의 약학적으로 허용가능한 염, 이의 제조방법 및 이를 유효성분으로 포함하는 유로텐신-Ⅱ 수용체 활성 관련 질환의 예방 또는 치료용 약학적 조성물

  摘要：

  This is the Chinese translation of the text you provided: 该发明涉及包含3,4-二氯苯基的乙酰胺衍生物或其药学上可接受的盐，其制备方法以及包含其作为有效成分的用于预防或治疗与欧洲肽Ⅱ受体活性相关的疾病的药学组合物。根据本发明，包含3,4-二氯苯基的乙酰胺衍生物通过作为欧洲肽Ⅱ受体的拮抗剂而可用于预防或治疗与欧洲肽Ⅱ受体活性相关的疾病，如充血性心力衰竭、心脏缺血、心肌梗死、心肌肥大、心脏纤维化、冠状动脉疾病、动脉硬化、高血压、哮喘、肾功能衰竭、糖尿病、血管炎、神经退行性疾病、脑卒中、疼痛、抑郁症、精神疾病、癌症等。

  公开号：

  KR101664281B1

文献信息

• MORPHOLINYL AND PYRROLIDINYL ANALOGS
  申请人：Goodman Krista B.

  公开号：US20080021023A1

  公开（公告）日：2008-01-24

  The present invention relates to morpholinyl, and pyrrolidinyl analogs, pharmaceutical compositions containing them, and their use as antagonists of urotensin II.

  本发明涉及吗吗啉基和吡咯啉基类似物，含有它们的药物组合物，以及它们作为尿苷II拮抗剂的用途。
• Morpholinyl and pyrrolidinyl analogs
  申请人：GlaxoSmithKline LLC

  公开号：US07749998B2

  公开（公告）日：2010-07-06

  The present invention relates to morpholinyl, and pyrrolidinyl analogs, pharmaceutical compositions containing them, and their use as antagonists of urotensin II.

  本发明涉及吗啡啶基和吡咯烷基类似物，含有它们的制药组合物，以及它们作为尿加压素II拮抗剂的用途。
• Development of potent and selective small-molecule human Urotensin-II antagonists
  作者：John J. McAtee、Jason W. Dodson、Sarah E. Dowdell、Gerald R. Girard、Krista B. Goodman、Mark A. Hilfiker、Clark A. Sehon、Deyou Sha、Gren Z. Wang、Ning Wang、Andrew Q. Viet、Daohua Zhang、Nambi V. Aiyar、David J. Behm、Luz H. Carballo、Christopher A. Evans、Harvey E. Fries、Rakesh Nagilla、Theresa J. Roethke、Xiaoping Xu、Catherine C.K. Yuan、Stephen A. Douglas、Michael J. Neeb

  DOI：10.1016/j.bmcl.2008.05.027

  日期：2008.6

  This work describes the development of potent and selective human Urotensin-II receptor antagonists starting from lead compound 1, (3,4-dichlorophenyl) methyl2-oxo-2-[3-phenyl-2-(1-pyrrolidinylmethyl)1-piperidinyl]ethyl}amine. Several problems relating to oral bioavailability, cytochrome P450 inhibition, and off-target activity at the kappa opioid receptor and cardiac sodium channel were addressed during lead development. hUT binding affinity relative to compound 1 was improved by more than 40-fold in some analogs, and a structural modi. cation was identified which significantly attenuated both off-target activities. (C) 2008 Elsevier Ltd. All rights reserved.
• US7432258B2
  申请人：——

  公开号：US7432258B2

  公开（公告）日：2008-10-07
• US7749998B2
  申请人：——

  公开号：US7749998B2

  公开（公告）日：2010-07-06