(S)-3-(甲硫基)吡咯烷-3-甲酸甲酯 | 1093063-61-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 中文名称: (S)-3-(甲硫基)吡咯烷-3-甲酸甲酯
• 英文名称: methyl (S)-3-(methylthio)pyrrolidine-3-carboxylate
• 英文别名: (S)-Methyl 3-(methylthio)pyrrolidine-3-carboxylate；methyl (3S)-3-methylsulfanylpyrrolidine-3-carboxylate
• CAS: 1093063-61-6
• 化学式: C₇H₁₃NO₂S
• 分子量: 175.252
• InChiKey: GEGOSBPKDSOSGF-ZETCQYMHSA-N

物化性质

• 沸点：
  247.7±40.0 °C(Predicted)
• 密度：
  1.15±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  11
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-3-(甲硫基)吡咯烷-3-甲酸甲酯 在 水 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 三氟乙酸 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 (3S)-N-[3-(4-fluorophenyl)-1H-indazol-5-yl]-3-methylsulfanylpyrrolidine-3-carboxamide
  参考文献：
  名称：

  Discovery of 3( S )-thiomethyl pyrrolidine ERK inhibitors for oncology

  摘要：

  Compound 5 (SCH772984) was identified as a potent inhibitor of ERK1/2 with excellent selectivity against a panel of kinases (0/231 kinases tested @ 100 nM) and good cell proliferation activity, but suffered from poor PK (rat AUC PK @10 mpk = 0 mu M h; F% = 0) which precluded further development. In an effort to identify novel ERK inhibitors with improved PK properties with respect to 5, a systematic exploration of sterics and composition at the 3-position of the pyrrolidine led to the discovery of a novel 3(S)-thiomethyl pyrrolidine analog 28 with vastly improved PK (rat AUC PK @10 mpk = 26 mu M h; F% = 70). (C) 2018 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2018.04.063
• 作为产物：
  描述：

  2-Methylmercapto-acrylsaeure-methylester 在 L-酒石酸 、 1-chloroethyl formate 、 1,8-双二甲氨基萘 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 72.0h， 生成 (S)-3-(甲硫基)吡咯烷-3-甲酸甲酯
  参考文献：
  名称：

  Discovery of 3( S )-thiomethyl pyrrolidine ERK inhibitors for oncology

  摘要：

  Compound 5 (SCH772984) was identified as a potent inhibitor of ERK1/2 with excellent selectivity against a panel of kinases (0/231 kinases tested @ 100 nM) and good cell proliferation activity, but suffered from poor PK (rat AUC PK @10 mpk = 0 mu M h; F% = 0) which precluded further development. In an effort to identify novel ERK inhibitors with improved PK properties with respect to 5, a systematic exploration of sterics and composition at the 3-position of the pyrrolidine led to the discovery of a novel 3(S)-thiomethyl pyrrolidine analog 28 with vastly improved PK (rat AUC PK @10 mpk = 26 mu M h; F% = 70). (C) 2018 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2018.04.063

文献信息

• MK-8353: Discovery of an Orally Bioavailable Dual Mechanism ERK Inhibitor for Oncology
  作者：Sobhana Babu Boga、Yongqi Deng、Liang Zhu、Yang Nan、Alan B. Cooper、Gerald W. Shipps、Ronald Doll、Neng-Yang Shih、Hugh Zhu、Robert Sun、Tong Wang、Sunil Paliwal、Hon-Chung Tsui、Xiaolei Gao、Xin Yao、Jagdish Desai、James Wang、Abdul Basit Alhassan、Joseph Kelly、Mehul Patel、Kiran Muppalla、Subrahmanyam Gudipati、Li-Kang Zhang、Alexei Buevich、David Hesk、Donna Carr、Priya Dayananth、Stuart Black、Hong Mei、Kathleen Cox、Bradley Sherborne、Alan W. Hruza、Li Xiao、Weihong Jin、Brian Long、Gongjie Liu、Stacey A. Taylor、Paul Kirschmeier、William T. Windsor、Robert Bishop、Ahmed A. Samatar

  DOI：10.1021/acsmedchemlett.8b00220

  日期：2018.7.12

  rapidly growing interest in discovering novel pathways to treat cancer. Toward this aim, a novel series of pyrrolidine derivatives (compound 5) were identified as potent inhibitors of ERK1/2 with excellent kinase selectivity and dual mechanism of action but suffered from poor pharmacokinetics (PK). The challenge of PK was overcome by the discovery of a novel 3(S)-thiomethyl pyrrolidine analog 7. Lead

  新的免疫癌症治疗方法的出现和发展引发了人们对发现治疗癌症新途径的兴趣迅速增长。为了实现这一目标，已鉴定出一系列新的吡咯烷衍生物（化合物5）为有效的ERK1 / 2抑制剂，具有出色的激酶选择性和双重作用机制，但药代动力学（PK）较差。通过发现新的3（S）-硫代甲基吡咯烷类似物7克服了PK的挑战。通过聚焦的结构-活性关系优化前导，导致发现了适用于每日两次口服给药的MK-8353临床候选药物，作为潜在的新型癌症治疗药物。
• Novel compounds that are ERK inhibitors
  申请人：Cooper Alan B.

  公开号：US20090118284A1

  公开（公告）日：2009-05-07

  Disclosed are the ERK inhibitors of formula 1.0: and the pharmaceutically acceptable salts, esters and solvates thereof. Q is a piperidine or piperazine ring that can have a bridge or a fused ring. The piperidine ring can have a double bond in the ring. All other substitutents are as defined herein. Also disclosed are methods of treating cancer using the compounds of formula 1.0.

  本发明公开了式1.0的ERK抑制剂及其药学上可接受的盐、酯和溶剂化物。其中，Q是一个带有桥或融合环的哌啶或哌嗪环。哌啶环中可以在环上具有双键。所有其他取代基如本文所定义。本发明还公开了使用式1.0的化合物治疗癌症的方法。
• NOVEL COMPOUNDS THAT ARE ERK INHIBITORS
  申请人：Cooper Alan B.

  公开号：US20110189192A1

  公开（公告）日：2011-08-04

  Disclosed are the ERK inhibitors of formula 1.0: and the pharmaceutically acceptable salts, and solvates thereof. Q is a tetrahydropyridinyl ring. All other substitutents are as defined herein. Also disclosed are methods of treating cancer using the compounds of formula 1.0.

  本发明公开了化学式1.0的ERK抑制剂，以及其药学上可接受的盐和溶剂化物。其中，Q代表四氢吡啶环。所有其他取代基的定义如本文所述。此外，本发明还公开了使用化合物1.0治疗癌症的方法。
• POLYCYCLIC INDAZOLE DERIVATIVES AND THEIR USE AS ERK INHIBITORS FOR THE TREATMENT OF CANCER
  申请人：Merck Sharp & Dohme Corp.

  公开号：EP2155722B1

  公开（公告）日：2013-08-14
• US8546404B2
  申请人：——

  公开号：US8546404B2

  公开（公告）日：2013-10-01