(2S,4R)-tert-butyl 2-ethynyl-4-hydroxypyrrolidine-1-carboxylate | 275387-80-9

• 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: (2S,4R)-tert-butyl 2-ethynyl-4-hydroxypyrrolidine-1-carboxylate
• 英文别名: tert-butyl (2S,4R)-2-ethynyl-4-hydroxypyrrolidine-1-carboxylate；(3R,5S)-N-Boc-3-Hydroxy-5-ethynyl-pyrrolidine
• CAS: 275387-80-9
• 化学式: C₁₁H₁₇NO₃
• 分子量: 211.261
• InChiKey: PEEDRTKUXJHIQB-RKDXNWHRSA-N

物化性质

• 沸点：
  297.2±40.0 °C(Predicted)
• 密度：
  1.13±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (2S,4R)-tert-butyl 2-ethynyl-4-hydroxypyrrolidine-1-carboxylate 在 copper(l) iodide 、 叠氮基三甲基硅烷 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 以74%的产率得到(2S,4R)-tert-butyl 4-hydroxy-2-(1H-1,2,3-triazol-5-yl)pyrrolidine-1-carboxylate
  参考文献：
  名称：

  脯氨酸衍生的氨基三唑配体：在钌催化的不对称转移加氢中的制备和使用

  摘要：

  2-三唑基和由2- triazolylmethylpyrrolidines的制备大号脯氨酸和大号-反式-4-羟基脯氨酸进行了说明，以它们作为钌催化不对称转移氢化手性配体的评价沿。还介绍了通过引入远程取代基进行配体的模块化演化，显示出对配体性能的出乎意料的重要影响。

  DOI：

  10.1002/adsc.201000678
• 作为产物：
  描述：

  tert-butyl (2S,4R)-4-((tert-butyldiphenylsilyl)oxy)-2-ethynylpyrrolidine-1-carboxylate 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 以90%的产率得到(2S,4R)-tert-butyl 2-ethynyl-4-hydroxypyrrolidine-1-carboxylate
  参考文献：
  名称：

  Synthesis and stereochemical effects of pyrrolidinyl-acetylenic thieno[3,2-d]pyrimidines as EGFR and ErbB-2 inhibitors

  摘要：

  A novel class of pyrrolidinyl-acetyleneic thieno[3,2-d]pyrimidines has been identified which potently inhibit the EGFR and ErbB-2 receptor tyrosine kinases. Synthetic modifications of the pyrrolidine carbamate moiety result in a range of effects on enzyme and cellular potency. In addition, the impact of the absolute stereochemical configuration on cellular potency and oral mouse pharmacokinetics is described. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.11.023

文献信息

• THERAPEUTIC AGENT FOR FGFR INHIBITOR-RESISTANT CANCER
  申请人：TAIHO PHARMACEUTICAL CO., LTD.

  公开号：US20160136168A1

  公开（公告）日：2016-05-19

  The problem to be solved by the present invention is to provide an anticancer agent for treating tumors resistant to other antitumor agents that inhibit FGFR, and a method for treating such tumors. The present invention provides an antitumor agent for administration to a tumor patient resistant to an FGFR inhibitor, the antitumor agent comprising a 3,5-disubstituted benzene alkynyl compound represented by Formula (I) below or a salt thereof. The present invention also provides a therapeutic method using the anticancer agent.

  本发明要解决的问题是提供一种用于治疗对抑制FGFR的其他抗肿瘤药物产生耐药的肿瘤的抗癌剂，以及一种治疗这种肿瘤的方法。本发明提供了一种用于给耐受FGFR抑制剂的肿瘤患者使用的抗肿瘤药物，该抗肿瘤药物包括下面的式(I)所代表的3,5-二取代苯基炔基化合物或其盐。本发明还提供了使用这种抗癌剂的治疗方法。
• ANTITUMOR DRUG FOR INTERMITTENT ADMINISTRATION OF FGFR INHIBITOR
  申请人：TAIHO PHARMACEUTICAL CO., LTD.

  公开号：US20160193210A1

  公开（公告）日：2016-07-07

  The problem to be solved by the present invention is to provide a potent and highly selective novel FGFR inhibitor, and an antitumor agent having reduced side effects, such as increased blood phosphorus levels, while maintaining the antitumor effect of the FGFR inhibitor. The present invention provides an antitumor agent comprising a 3,5-disubstituted benzene alkynyl compound represented by Formula (I) or a salt thereof that is used so that the 3,5-disubstituted benzene alkynyl compound or a salt thereof is administered on an administration schedule of at least twice a week and a dosing interval of at least one day.

  本发明要解决的问题是提供一种有效且高选择性的新型FGFR抑制剂，以及具有减少副作用（如增加血磷水平）的抗肿瘤药剂，同时保持FGFR抑制剂的抗肿瘤效果。本发明提供了一种抗肿瘤药剂，包括由式（I）表示的3,5-二取代苯基炔基化合物或其盐，该药剂用于按照至少每周两次和至少间隔一天的给药计划给予3,5-二取代苯基炔基化合物或其盐。
• 4-Alkenyl- and 4-alkynyloxindoles
  申请人：Hoffmann-La Roche Inc.

  公开号：US06130239A1

  公开（公告）日：2000-10-10

  Disclosed are novel 4-alkenyl- and 4-alkynyl oxindoles having the formula ##STR1## and the pharmaceutically acceptable salts thereof, wherein R.sup.1, R.sup.2, R.sup.3, a, b, and X are as defined herein. These compounds inhibit cyclin-dependent kinases (CDKs), in particular CDK2. These compounds and their pharmaceutically acceptable salts, and prodrugs of said compounds, are anti-proliferative agents useful in the treatment or control of cell proliferative disorders, in particular cancer, more particularly, the treatment or control of breast and colon tumors. Also disclosed are pharmaceutical compositions containing the compounds of formula I and II as well as intermediates useful in the preparation of the compounds of formula I and II.

  揭示了具有以下结构式的新型4-烯基和4-炔基吲哚化合物及其药学上可接受的盐，其中R.sup.1、R.sup.2、R.sup.3、a、b和X如本文所定义。这些化合物抑制细胞周期依赖性激酶（CDKs），特别是CDK2。这些化合物及其药学上可接受的盐，以及这些化合物的前药，是用于治疗或控制细胞增殖性疾病的抗增殖剂，特别是癌症，更具体地说是用于治疗或控制乳腺和结肠肿瘤。还披露了含有结构式I和II化合物的药物组合物，以及在制备结构式I和II化合物中有用的中间体。
• [EN] 4-ALKENYL (AND ALKYNYL) OXINDOLES AS INHIBITORS OF CYCLIN-DEPENDENT KINASES, IN PARTICULAR CDK2<br/>[FR] 4-ALCENYL (ET ALCYNYL) OXINDOLES UTILISES COMME INHIBITEURS DE KINASES DEPENDANTES DES CYCLINES, EN PARTICULIER LA CDK2
  申请人：HOFFMANN LA ROCHE

  公开号：WO2000035908A1

  公开（公告）日：2000-06-22

  Novel 4-alkenyl- and 4-alkynyl oxindoles having formulas (I) and (II) and the pharmaceutically acceptable salts thereof, wherein R?1, R2, R3¿, a, b, and X are as defined herein inhibit cyclin-dependent kinases (CDKs), in particular CDK2 and are useful as anti-proliferative agents in the treatment or control of cell proliferative disorders, in particular breast and colon tumors.

  具有以下化学式（I）和（II）以及其药学上可接受的盐的新型4-烯基和4-炔基氧吲哚，其中R?1，R2，R3¿，a，b和X如此定义，抑制细胞周期依赖性激酶（CDKs），特别是CDK2，并且在治疗或控制细胞增殖性疾病，特别是乳腺和结肠肿瘤中作为抗增殖剂是有用的。
• 4-alkenyl-and 4-alkynyloxindoles
  申请人：Hoffmann-La Roche Inc.

  公开号：US06252086B1

  公开（公告）日：2001-06-26

  Disclosed are novel 4-alkenyl- and 4-alkynyl oxindoles having the formula and the pharmaceutically acceptable salts thereof. These compounds inhibit cyclin-dependent kinases (CDKs), in particular CDK2. These compounds and their pharmaceutically acceptable salts, and prodrugs of said compounds, are anti-proliferative agents useful in the treatment or control of cell proliferative disorders, in particular cancer, more particularly, the treatment or control of breast and colon tumors. Also disclosed are pharmaceutical compositions containing the compounds of formula I and II as well as intermediates useful in the preparation of the compounds of formula I and II.

  本发明涉及具有以下公式和其药学上可接受的盐的新型4-烯基和4-炔基氧吲哚。这些化合物抑制细胞周期蛋白依赖性激酶（CDKs），特别是CDK2。这些化合物及其药学上可接受的盐和前药是抗增殖剂，可用于治疗或控制细胞增殖性疾病，特别是癌症，更特别是乳腺和结肠肿瘤的治疗或控制。本发明还涉及包含公式I和II的化合物的制药组合物，以及制备公式I和II的化合物的中间体。