(2R,4S)-4-[(4-fluorophenyl)methyl]-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid | 1229439-70-6

• 物质功能分类: 有机原料 - 羧酸类化合物及衍生物
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2R,4S)-4-[(4-fluorophenyl)methyl]-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid
• CAS: 1229439-70-6
• 化学式: C₁₇H₂₂FNO₄
• 分子量: 323.364
• InChiKey: FGLYPQZHYLRBOI-GXTWGEPZSA-N

物化性质

• 沸点：
  452.1±35.0 °C(Predicted)
• 密度：
  1.235±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2R,4S)-4-[(4-fluorophenyl)methyl]-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid 在 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 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.5h， 生成 (2R,4S)-1-(2-(1H-1,2,3-triazol-1-yl)acetyl)-4-(4-fluorobenzyl)-N-(4-(4-fluorophenoxy)phenyl)pyrrolidine-2-carboxamide
  参考文献：
  名称：

  Discovery of a Novel Class of Potent and Orally Bioavailable Sphingosine 1-Phosphate Receptor 1 Antagonists

  摘要：

  A series of subtype selective sphingosine 1-phosphate receptor 1 (S1P(1)) antagonists are disclosed. Our high-throughput screening campaign revealed hit 1 for which an increase in potency and mouse oral exposure was achieved with minor modifications to the chemical scaffold. In vivo efficacy revealed that at high doses compounds 12 and 15 inhibited tumor growth. Further optimization of our lead series led to the discovery of proline derivatives 37 (XL541) and 38 which had similar efficacy as our first generation analogues at significantly lower doses. Analogue 37 displayed excellent pharmacokinetics and oral exposure in multiple species.

  DOI：

  10.1021/jm201533b
• 作为产物：
  描述：

  D-焦谷氨酸 在 甲醇 、 4-二甲氨基吡啶 、 三乙基硼氢化锂 、 对甲苯磺酸 、 potassium hydroxide 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 57.08h， 生成 (2R,4S)-4-[(4-fluorophenyl)methyl]-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid
  参考文献：
  名称：

  Discovery of a Novel Class of Potent and Orally Bioavailable Sphingosine 1-Phosphate Receptor 1 Antagonists

  摘要：

  A series of subtype selective sphingosine 1-phosphate receptor 1 (S1P(1)) antagonists are disclosed. Our high-throughput screening campaign revealed hit 1 for which an increase in potency and mouse oral exposure was achieved with minor modifications to the chemical scaffold. In vivo efficacy revealed that at high doses compounds 12 and 15 inhibited tumor growth. Further optimization of our lead series led to the discovery of proline derivatives 37 (XL541) and 38 which had similar efficacy as our first generation analogues at significantly lower doses. Analogue 37 displayed excellent pharmacokinetics and oral exposure in multiple species.

  DOI：

  10.1021/jm201533b

文献信息

• 作为MASP-2抑制剂的化合物、药物组合物及其制备方法和用途
  申请人：武汉朗来科技发展有限公司

  公开号：CN116514772A

  公开（公告）日：2023-08-01

  本发明涉及具有补体凝集素途径抑制活性的化合物、其制备方法及其应用。具体而言，本发明涉及一种通式(I’)所示的化合物、其药学上可接受的盐、其制备方法及其作为MASP‑2抑制剂的应用，特别是在制备治疗IgA肾病、TA‑TMA、aHUS、狼疮性肾炎等疾病的药物的应用。
• Novel substituted pyrrolidines are high affinity histamine H3 receptor antagonists
  作者：Emily M. Stocking、Leah Aluisio、John R. Atack、Pascal Bonaventure、Nicholas I. Carruthers、Christine Dugovic、Anita Everson、Ian Fraser、Xiaohui Jiang、Perry Leung、Brian Lord、Kiev S. Ly、Kirsten L. Morton、Diane Nepomuceno、Chandravadan R. Shah、Jonathan Shelton、Akinola Soyode-Johnson、Michael A. Letavic

  DOI：10.1016/j.bmcl.2010.03.071

  日期：2010.5

  Pre-clinical characterization of novel substituted pyrrolidines that are high affinity histamine H-3 receptor antagonists is described. These compounds efficiently penetrate the CNS and occupy the histamine H-3 receptor in rat brain following oral administration. One compound, (2S,4R)-1-[2-(4-cyclobutyl-[1,4]diazepane-1-carbonyl)-4-(3-fluoro-phenoxy)-pyrrolidin-1-yl]-ethanone, was extensively profiled and shows promise as a potential clinical candidate. (C) 2010 Elsevier Ltd. All rights reserved.