4-((2S)-2-methoxymethylpyrrolidin-1-yl)but-2-ynoic acid | 263148-94-3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: 4-((2S)-2-methoxymethylpyrrolidin-1-yl)but-2-ynoic acid
• 英文别名: 4-[(2S)-2-(methoxymethyl)-1-pyrrolidinyl]-2-butynoic acid；4-((2S)-2-methoxymethylpyrrolidin-1-yl)butynoic acid；4-[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]but-2-ynoic acid
• CAS: 263148-94-3
• 化学式: C₁₀H₁₅NO₃
• 分子量: 197.234
• InChiKey: KYGHAVTVJIZAGB-VIFPVBQESA-N

物化性质

• 沸点：
  326.0±17.0 °C(Predicted)
• 密度：
  1.145±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.6
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-((2S)-2-methoxymethylpyrrolidin-1-yl)but-2-ynoic acid 在 N-甲基吗啉 作用下， 以 四氢呋喃 为溶剂， 反应 3.25h， 生成 4-((2S)-2-methoxymethylpyrrolidin-1-yl)but-2-ynoic acid [4-(3-bromophenylamino)-3-cyanoquinolin-6-yl]amide
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of 6,7-Disubstituted 4-Anilinoquinoline-3-carbonitriles. The Design of an Orally Active, Irreversible Inhibitor of the Tyrosine Kinase Activity of the Epidermal Growth Factor Receptor (EGFR) and the Human Epidermal Growth Factor Receptor-2 (HER-2)

  摘要：

  A series of of 6,7-disubstituted-4-anilinoquinoline-3-carbonitrile derivatives that function as irreversible inhibitors of EGFR and HER-2 kinases have been prepared. These inhibitors have, at the 6-position, butynamide, crotonamide, and methacrylamide Michael acceptors bearing water-solublilizing substituents. These compounds were prepared by acylation of 6-amino-4-(arylamino)quinoline-3-carbonitriles with unsaturated acid chlorides or mixed anhydrides. We performed competitive reactivity studies showing that attaching a dialkylamino group onto the end of the Michael acceptor results in compounds with greater reactivity due to intramolecular catalysis of the Michael addition. This, along with improved water-solubility results in compounds with enhanced biological properties. We present molecular modeling results consistent with the proposed mechanism of inhibition. One compound, 5 (EKB-569), which shows excellent oral in vivo activity, was selected for further studies and is currently in phase I clinical trials for the treatment of cancer.

  DOI：

  10.1021/jm020241c
• 作为产物：
  描述：

  3-[(2S)-2-(methoxymethyl)-1-pyrrolidinyl]-1-propyne 在 正丁基锂 、 二氧化碳 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 1.17h， 生成 4-((2S)-2-methoxymethylpyrrolidin-1-yl)but-2-ynoic acid
  参考文献：
  名称：

  SUBSTITUTED-3-CYANO-[1.7],[1.5], AND [1.8]-NAPHTHYRIDINE INHIBITORS OF TYROSINE KINASES

  摘要：

  公开号：

  EP1171440B1

文献信息

• Substituted 3-cyanoquinolines as protein tyrosine kinases inhibitors
  申请人：Wyeth Holdings Corporation

  公开号：EP1950201A1

  公开（公告）日：2008-07-30

  This invention provides compounds of formula 1 wherein R1, G1, G2, R4, Z, X and n are defined herein, or a pharmaceutically acceptable salt thereof, which are useful as antineoplastic agents and in the treatment of polycystic kidney disease.

  这项发明提供了式1的化合物 其中R1、G1、G2、R4、Z、X和n在此处定义，或其药学上可接受的盐，这些化合物可用作抗肿瘤剂和多囊肾病的治疗药物。
• Substituted 3-cyanoquinolines
  申请人：American Cyanamid Company

  公开号：US06288082B1

  公开（公告）日：2001-09-11

  This invention provides compounds of formula I having the structure wherein G1, G2, R1, R4, Z, n, and X are defined in the specification or a pharmaceutically acceptable salt thereof which are useful as antineoplastic agents and in the treatment of polycystic kidney disease.

  这项发明提供了具有结构的化合物I的公式，其中G1、G2、R1、R4、Z、n和X在规范中定义，或其药用盐，这些化合物可用作抗肿瘤剂，并用于多囊肾病的治疗。
• 6-Substituted-4-(3-bromophenylamino)quinazolines as Putative Irreversible Inhibitors of the Epidermal Growth Factor Receptor (EGFR) and Human Epidermal Growth Factor Receptor (HER-2) Tyrosine Kinases with Enhanced Antitumor Activity
  作者：Hwei-Ru Tsou、Nellie Mamuya、Bernard D. Johnson、Marvin F. Reich、Brian C. Gruber、Fei Ye、Ramaswamy Nilakantan、Ru Shen、Carolyn Discafani、Ronald DeBlanc、Rachel Davis、Frank E. Koehn、Lee M. Greenberger、Yu-Fen Wang、Allan Wissner

  DOI：10.1021/jm0005555

  日期：2001.8.1

  A series of new 6-substituted-4-(3-bromophenylamino)quinazoline derivatives that may function as irreversible inhibitors of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor (HER-2) tyrosine kinases have been prepared. These inhibitors have, at the C-6 position, butynamide, crotonamide, and methacrylamide Michael acceptors bearing water-solublilizing substituents. These

  已经制备了一系列新的6-取代的4-（3-溴苯基氨基）喹唑啉衍生物，其可以用作表皮生长因子受体（EGFR）和人表皮生长因子受体（HER-2）酪氨酸激酶的不可逆抑制剂。这些抑制剂在C-6位具有带有水溶性增溶取代基的丁炔酰胺，巴豆酰胺和甲基丙烯酰胺迈克尔受体。这些化合物是通过将6-氨基-4-（3-溴苯基氨基）喹唑啉与不饱和酰氯或混合酸酐酰化而制备的。我们显示，由于迈克尔加成的分子内催化和/或质子化碱性基团的诱导作用，将碱性官能团附接到迈克尔受体上导致更大的反应性。加上改善的水溶性，产生具有增强的生物学特性的化合物。我们目前分子模型和实验证据，这些抑制剂与目标酶共价相互作用。一种化合物16a在裸鼠的人表皮样癌（A431）异种移植模型中显示具有出色的口服活性。
• Substituted 3-cyano-[1.7],[1.5], and [1.8] naphthyridine inhibitors of tyrosine kinases
  申请人：American Cyanamid Company

  公开号：US06355636B1

  公开（公告）日：2002-03-12

  This invention provides compounds of formula I having the structure useful as inhibitors of protein tyrosine kinase.

  这项发明提供了具有结构的化合物，可作为蛋白酪氨酸激酶抑制剂。
• [EN] SUBSTITUTED 3-CYANOQUINOLINES AS PROTEIN TYROSINE KINASES INHIBITORS<br/>[FR] INHIBITEURS DE PROTEINES DE TYPE TYROSINE KINASES A BASE DE 3-CYANOQUINOLINES SUBSTITUEES
  申请人：AMERICAN CYANAMID CO

  公开号：WO2000018761A1

  公开（公告）日：2000-04-06

  This invention provides compounds of formula (1) wherein R1, G1, G2, R4, Z, X and n are defined herein, or a pharmaceutically acceptable salt thereof, which are useful as antineoplastic agents and in the treatment of polycystic kidney disease.

  该发明提供了式（1）的化合物，其中R1、G1、G2、R4、Z、X和n在此定义，或其药学上可接受的盐，可用作抗肿瘤剂以及多囊肾病的治疗。