methyl (S)-3-(pyrrolidin-2-yl)propanoate | 689303-75-1

• 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: methyl (S)-3-(pyrrolidin-2-yl)propanoate
• 英文别名: Methyl 3-[(2S)-pyrrolidin-2-yl]propanoate
• CAS: 689303-75-1
• 化学式: C₈H₁₅NO₂
• 分子量: 157.213
• InChiKey: XCIURYKPJOJDBF-ZETCQYMHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  11
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl (S)-3-(pyrrolidin-2-yl)propanoate 在 三氟化硼乙醚 、 2,2,6,6-tetramethylpiperidinyl-lithium 、 sodium methylate 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 (2S,8S)-2-[(R)-hydroxy-(4-nitrophenyl)methyl]-1,2,5,6,7,8-hexahydropyrrolizin-3-one
  参考文献：
  名称：

  Asymmetric Baylis–Hillman reactions: catalysis using a chiral pyrrolizidine base

  摘要：

  衍生自 L-脯氨酸的新型手性吡咯里西啶碱基 5 可促进乙基和甲基乙烯基酮与缺电子芳香醛的 Baylis–Hillman 反应，并具有适度的对映体过量水平。

  DOI：

  10.1039/a806115g
• 作为产物：
  描述：

  (2S)-N-苄氧羰基-2-吡咯烷甲醛 在 palladium on activated charcoal 氢气 、 N,N-二异丙基乙胺 、 lithium chloride 作用下， 以 甲醇 、 乙腈 为溶剂， 20.0 ℃ 、100.0 kPa 条件下， 反应 17.0h， 生成 methyl (S)-3-(pyrrolidin-2-yl)propanoate
  参考文献：
  名称：

  New highly potent GABA uptake inhibitors selective for GAT-1 and GAT-3 derived from (R)- and (S)-proline and homologous pyrrolidine-2-alkanoic acids

  摘要：

  We synthesized proline and pyrrolidine-2-alkanoic acid derivatives in their enantiomerically pure form and evaluated them for their affinity to the GABA transport proteins GAT-1 and GAT-3. Among the compounds presented herein, (R)-pyrrolidine-2-acetic acid (R)-4d substituted with a 2- [tris(4-methoxyphenyl)methoxy] ethyl residue at the nitrogen atom showed the highest affinity at GAT-3 (IC50 = 3.1 mu M) comparable with the well-known GAT-3 blocker (S)-SNAP-5114. Compound (R)-4d displayed excellent subtype selectivity for GAT-3 (GAT-3:GAT-1 = 20:1). (S)-2-pyrrolidineacetic acid derivatives (S)-4b provided with a 4,4-diphenylbut-3-en-1-yl moiety and (S)-4c substituted with a 4,4-[di(3-methylthiophen-2-yl)]phenylbut-3-en-l-yl residue at the nitrogen atom exhibited IC50 values of 0.396 mu M and 0.343 mu M at the GAT-1 protein, respectively. (c) 2006 Elsevier SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2006.01.019

文献信息

• CHEMOKINE RECEPTOR MODULATORS AND USES THEREOF
  申请人：FLX Bio, Inc.

  公开号：US20180072743A1

  公开（公告）日：2018-03-15

  Disclosed herein, inter alia, are compounds and methods of use thereof for the modulation of chemokine receptor activity.

  披露的内容包括但不限于，用于调节趋化因子受体活性的化合物及其使用方法。
• Discovery of a Potent and Selective CCR4 Antagonist That Inhibits T_reg Trafficking into the Tumor Microenvironment
  作者：Jeffrey J. Jackson、John M. Ketcham、Ashkaan Younai、Betty Abraham、Berenger Biannic、Hilary P. Beck、Minna H. T. Bui、David Chian、Gene Cutler、Raymond Diokno、Dennis X. Hu、Scott Jacobson、Emily Karbarz、Paul D. Kassner、Lisa Marshall、Jenny McKinnell、Cesar Meleza、Abood Okal、Deepa Pookot、Maureen K. Reilly、Omar Robles、Hunter P. Shunatona、Oezcan Talay、James R. Walker、Angela Wadsworth、David J. Wustrow、Mikhail Zibinsky

  DOI：10.1021/acs.jmedchem.9b00506

  日期：2019.7.11

  the TME can potentiate antitumor immune responses. We developed a novel series of potent, orally bioavailable small molecule antagonists of CCR4. From this series, several compounds exhibited high potency in distinct functional assays in addition to good in vitro and in vivo ADME properties. The design, synthesis, and SAR of this series and confirmation of its in vivo activity are reported.

  将抑制性CD4 + FOXP3 +调节性T细胞（Treg）招募到肿瘤微环境（TME）可能会削弱接受免疫肿瘤学（IO）药物治疗的患者的抗肿瘤反应。人Treg表达CCR4，可以通过CC趋化因子配体CCL17和CCL22募集到TME。在某些癌症中，Treg积累与患者预后不良相关。临床前数据表明，防止Treg募集并增加TME中活化的效应T细胞（Teff）的数量可以增强抗肿瘤免疫反应。我们开发了一系列新颖的，有效的，口服生物利用的CCR4小分子拮抗剂。从该系列中，除了良好的体外和体内ADME特性外，几种化合物在独特的功能测定中还显示出强大的效用。设计，综合，
• Chemokine receptor modulators and uses thereof
  申请人：FLX Bio, Inc.

  公开号：US10246462B2

  公开（公告）日：2019-04-02

  Disclosed herein, inter alia, are compounds and methods of use thereof for the modulation of chemokine receptor activity.

  本文特别公开了用于调节趋化因子受体活性的化合物及其使用方法。
• [EN] CHEMOKINE RECEPTOR MODULATORS AND USES THEREOF<br/>[FR] MODULATEURS DES RÉCEPTEURS DE LA CHIMIOKINE ET LEURS UTILISATIONS
  申请人：FLX BIO INC

  公开号：WO2018049271A1

  公开（公告）日：2018-03-15

  Disclosed herein, inter alia, are compounds and methods of use thereof for the modulation of chemokine receptor activity.
• New highly potent GABA uptake inhibitors selective for GAT-1 and GAT-3 derived from (R)- and (S)-proline and homologous pyrrolidine-2-alkanoic acids
  作者：Günther H. Fülep、Cornelia E. Hoesl、Georg Höfner、Klaus T. Wanner

  DOI：10.1016/j.ejmech.2006.01.019

  日期：2006.7

  We synthesized proline and pyrrolidine-2-alkanoic acid derivatives in their enantiomerically pure form and evaluated them for their affinity to the GABA transport proteins GAT-1 and GAT-3. Among the compounds presented herein, (R)-pyrrolidine-2-acetic acid (R)-4d substituted with a 2- [tris(4-methoxyphenyl)methoxy] ethyl residue at the nitrogen atom showed the highest affinity at GAT-3 (IC50 = 3.1 mu M) comparable with the well-known GAT-3 blocker (S)-SNAP-5114. Compound (R)-4d displayed excellent subtype selectivity for GAT-3 (GAT-3:GAT-1 = 20:1). (S)-2-pyrrolidineacetic acid derivatives (S)-4b provided with a 4,4-diphenylbut-3-en-1-yl moiety and (S)-4c substituted with a 4,4-[di(3-methylthiophen-2-yl)]phenylbut-3-en-l-yl residue at the nitrogen atom exhibited IC50 values of 0.396 mu M and 0.343 mu M at the GAT-1 protein, respectively. (c) 2006 Elsevier SAS. All rights reserved.