(R)-1-(2-ethynylpyrrolidin-1-yl)ethan-1-one | 128960-01-0

• 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: (R)-1-(2-ethynylpyrrolidin-1-yl)ethan-1-one
• 英文别名: 1-[(2R)-2-Ethynylpyrrolidin-1-yl]ethanone
• CAS: 128960-01-0
• 化学式: C₈H₁₁NO
• 分子量: 137.181
• InChiKey: ZAFKSHSFIZAUGY-QMMMGPOBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (R)-1-(2-ethynylpyrrolidin-1-yl)ethan-1-one 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 N,N-二异丙基乙胺 、 间氯过氧苯甲酸 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 生成 tert-butyl (1R,4R,5S)-5-(2-((R)-1-acetylpyrrolidin-2-yl)-7-bromo-8-(2-cyanoethyl)-6-fluoro-4-((S)-1-((S)-1-methylpyrrolidin-2-yl)ethoxy)-1H-pyrrolo[3,2-c]quinolin-1-yl)-2-azabicyclo[2.1.1]hexane-2-carboxylate
  参考文献：
  名称：

  [EN] FUSED TRICYCLIC COMPOUNDS AS INHIBITORS OF KRAS G12V MUTANTS
  [FR] COMPOSÉS TRICYCLIQUES FUSIONNÉS EN TANT QU'INHIBITEURS DE MUTANTS KRAS G12V

  摘要：

  Dislcosed are compounds of Formula I, methods of using the compounds for inhibiting KRAS activity and pharmaceutical compositions comprising such compounds. The compounds are useful in treating, preventing or ameliorating diseases or disorders associated with KRAS activity such as cancer.

  公开号：

  WO2024015731A1
• 作为产物：
  描述：

  (R)-2-ethynylpyrrolidine oxalate 、 乙酰氯 在 三乙胺 作用下， 以 乙醚 为溶剂， 以76%的产率得到(R)-1-(2-ethynylpyrrolidin-1-yl)ethan-1-one
  参考文献：
  名称：

  轻松合成已分解的α-乙炔基取代的环胺

  摘要：

  已经通过包括关键阳极氧化步骤在内的简便方法合成了一系列拆分的α-炔基吡咯烷基，哌啶基和全氢a庚啶基衍生物。绝对构型的分配基于化学相关性和圆二色性光谱。

  DOI：

  10.1016/s0040-4039(00)94612-4

文献信息

• Identification of potent and selective oxytocin antagonists. Part 1: indole and benzofuran derivatives
  作者：Paul G Wyatt、Michael J Allen、Josie Chilcott、Alison Foster、David G Livermore、Jackie E Mordaunt、Jan Scicinski、Patrick M Woollard

  DOI：10.1016/s0960-894x(02)00159-2

  日期：2002.5

  novel, potent and selective oxytocin antagonists are reported. Combinatorial libraries designed to find novel replacements of fragments of oxytocin antagonist L-371,257, identified pyrimidine, thiazole, indole and benzofuran as potential alternatives to the benzoic acid moiety of L-371,257. Additional investigations identified indole and benzofuran derivatives with potent oxytocin antagonist activity

  报道了发现新颖，有效和选择性催产素拮抗剂的研究。设计用于寻找催产素拮抗剂L-371,257片段的新型替代物的组合文库，将嘧啶，噻唑，吲哚和苯并呋喃确定为L-371,257苯甲酸部分的潜在替代物。进一步的研究确定了具有有效催产素拮抗剂活性的吲哚和苯并呋喃衍生物。
• Resolved pyrrolidine, piperidine, and perhydroazepine analogs of the muscarinic agent N-methyl-N-(1-methyl-4-pyrrolidino-2-butynyl)acetamide
  作者：J. R. Michael Lundkvist、Hugo M. Vargas、Patrizia Caldirola、Bjoern Ringdahl、Uli Hacksell

  DOI：10.1021/jm00174a014

  日期：1990.12

  A series of conformationally restricted analogues of the partial muscarinic agonist N-methyl-N-(1-methyl-4-pyrrolidino-2-butynyl)acetamide (BM 5; 1) was synthesized. Three of the racemic derivatives were resolved into the enantiomers. The compounds were investigated for muscarinic and antimuscarinic activity in the isolated guinea pig ileum. They were found to be fairly potent muscarinic antagonists or weak partial agonists. The new compounds were either equally or less potent than 1 in inhibiting (-)-[3H]-N-methylscopolamine binding in homogenates of the rat cerebral cortex. Thus, structural modifications to 1 in which the amide moiety and the methyl group in the butynyl chain have been joined to form a six- or seven-membered ring preserve affinity but abolish efficacy. The R enantiomers were found to have 14-79 times higher affinity to ileal muscarinic receptors than the respective antipodes. The enantiomeric affinity ratios were nearly identical in both preparations studied. As suggested by molecular mechanics calculations, the difference in affinity between the five-membered and the six- and seven-membered ring analogues may be rationalized in conformational terms.
• LUNDKVIST, J. R. M.;WISTRAND, L. -G.;HACKSELL, U., TETRAHEDRON LETT., 31,(1990) N, C. 719-722
  作者：LUNDKVIST, J. R. M.、WISTRAND, L. -G.、HACKSELL, U.

  DOI：——

  日期：——
• LUNDKVIST, J. R. MICHAEL;VARGAS, HUGO M.;CALDIROLA, PATRIZIA;RINGDAHL, BJ+, J. MED. CHEM., 33,(1990) N2, C. 3182-3189
  作者：LUNDKVIST, J. R. MICHAEL、VARGAS, HUGO M.、CALDIROLA, PATRIZIA、RINGDAHL, BJ+

  DOI：——

  日期：——
• [EN] QUINOLINE COMPOUNDS AS INHIBITORS OF KRAS<br/>[FR] COMPOSÉS DE QUINOLÉINE UTILES EN TANT QU'INHIBITEURS DE KRAS
  申请人：[en]INCYTE CORPORATION

  公开号：WO2023064857A1

  公开（公告）日：2023-04-20

  Disclosed are compounds of Formula I, methods of using the compounds for inhibiting KRAS activity and pharmaceutical compositions comprising such compounds. The compounds are useful in treating, preventing or ameliorating diseases or disorders associated with KRAS activity such as cancer.