(S)-methyl-2-amino-3-(3,5-bis(trifluoromethyl)phenyl)propanoate | 1213850-58-8

• 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: (S)-methyl-2-amino-3-(3,5-bis(trifluoromethyl)phenyl)propanoate
• 英文别名: (S)-3-(3,5-bis(trifluoromethyl)phenyl)-2-aminopropanoic acid methyl ester；(S)-2-amino-3-(3,5-bis(trifluoromethyl)phenyl)propionic acid methyl ester；methyl (2S)-2-amino-3-[3,5-bis(trifluoromethyl)phenyl]propanoate
• CAS: 1213850-58-8
• 化学式: C₁₂H₁₁F₆NO₂
• 分子量: 315.215
• InChiKey: FWGNALOEYDPUGD-VIFPVBQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  52.3
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (S)-methyl-2-amino-3-(3,5-bis(trifluoromethyl)phenyl)propanoate 在 盐酸 、 lithium hydroxide monohydrate 、 1-羟基苯并三唑 作用下， 以 甲醇 、 正己烷 、 二氯甲烷 、 水 为溶剂， 反应 56.34h， 生成 ((R)-1-((S)-3-(3,5-bis(trifluoromethyl)phenyl)-2-(2,5-dichlorobenzamido)propanamido)-3-methylbutyl)boronic acid
  参考文献：
  名称：

  3D-QSAR-aided design, synthesis, in vitro and in vivo evaluation of dipeptidyl boronic acid proteasome inhibitors and mechanism studies

  摘要：

  Proteasome had been clinically validated as an effective target for the treatment of cancers. Up to now, many structurally diverse proteasome inhibitors were discovered. And two of them were launched to treat multiple myeloma (MM) and mantle cell lymphoma (MCL). Based on our previous biological results of dipeptidyl boronic acid proteasome inhibitors, robust 3D-QSAR models were developed and structure-activity relationship (SAR) was summarized. Several structurally novel compounds were designed based on the theoretical models and finally synthesized. Biological results showed that compound 12e was as active as the standard bortezomib in enzymatic and cellular activities. In vivo pharmacokinetic profiles suggested compound 12e showed a long half-life, which indicated that it could be administered intravenously. Cell cycle analysis indicated that compound 12e inhibited cell cycle progression at the G2M stage. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2016.04.025
• 作为产物：
  描述：

  methyl (S)-3-(3,5-bis(trifluoromethyl)phenyl)-2-(1,3-dioxoisoindolin-2-yl)propanoate 在 乙二胺 作用下， 以 甲醇 为溶剂， 反应 9.0h， 以75.8%的产率得到(S)-methyl-2-amino-3-(3,5-bis(trifluoromethyl)phenyl)propanoate
  参考文献：
  名称：

  3D-QSAR-aided design, synthesis, in vitro and in vivo evaluation of dipeptidyl boronic acid proteasome inhibitors and mechanism studies

  摘要：

  Proteasome had been clinically validated as an effective target for the treatment of cancers. Up to now, many structurally diverse proteasome inhibitors were discovered. And two of them were launched to treat multiple myeloma (MM) and mantle cell lymphoma (MCL). Based on our previous biological results of dipeptidyl boronic acid proteasome inhibitors, robust 3D-QSAR models were developed and structure-activity relationship (SAR) was summarized. Several structurally novel compounds were designed based on the theoretical models and finally synthesized. Biological results showed that compound 12e was as active as the standard bortezomib in enzymatic and cellular activities. In vivo pharmacokinetic profiles suggested compound 12e showed a long half-life, which indicated that it could be administered intravenously. Cell cycle analysis indicated that compound 12e inhibited cell cycle progression at the G2M stage. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2016.04.025

文献信息

• SYNTHESIS AND USES OF PEPTIDE BORATE ESTER COMPOUND
  申请人：Jiangsu Chia Tai Fenghai Pharmaceutical Co., Ltd.

  公开号：EP3805237A1

  公开（公告）日：2021-04-14

  Provided are a peptide borate ester compound or a pharmaceutically acceptable salt thereof, a preparation method therefor, and pharmaceutical use thereof. The peptide borate ester compound or pharmaceutically acceptable salt thereof has a structure as shown in Formula (I), and is useful in the preparation of proteasome inhibitors to treat solid tumors and hematoma.

  本文提供了一种肽硼酸酯化合物或其药学上可接受的盐、其制备方法及其药物用途。肽硼酸酯化合物或其药学上可接受的盐具有如式（I）所示的结构，可用于制备蛋白酶体抑制剂以治疗实体瘤和血肿。
• SYNTHESIS OF PEPTIDE BORATE ESTER COMPOUND AND USE THEREOF
  申请人：JIANGSU CHIA TAI FENGHAI PHARMACEUTICAL CO., LTD.

  公开号：US20210214377A1

  公开（公告）日：2021-07-15

  Provided are a peptide borate ester compound or a pharmaceutically acceptable salt thereof, a preparation method therefor, and pharmaceutical use thereof. The peptide borate ester compound or pharmaceutically acceptable salt thereof has a structure as shown in Formula (I), and is useful in the preparation of proteasome inhibitors to treat solid tumors and hematoma.
• 3D-QSAR-aided design, synthesis, in vitro and in vivo evaluation of dipeptidyl boronic acid proteasome inhibitors and mechanism studies
  作者：Meng Lei、Huayun Feng、Cheng Wang、Hailing Li、Jingmiao Shi、Jia Wang、Zhaogang Liu、Shanshan Chen、Shihe Hu、Yongqiang Zhu

  DOI：10.1016/j.bmc.2016.04.025

  日期：2016.6

  Proteasome had been clinically validated as an effective target for the treatment of cancers. Up to now, many structurally diverse proteasome inhibitors were discovered. And two of them were launched to treat multiple myeloma (MM) and mantle cell lymphoma (MCL). Based on our previous biological results of dipeptidyl boronic acid proteasome inhibitors, robust 3D-QSAR models were developed and structure-activity relationship (SAR) was summarized. Several structurally novel compounds were designed based on the theoretical models and finally synthesized. Biological results showed that compound 12e was as active as the standard bortezomib in enzymatic and cellular activities. In vivo pharmacokinetic profiles suggested compound 12e showed a long half-life, which indicated that it could be administered intravenously. Cell cycle analysis indicated that compound 12e inhibited cell cycle progression at the G2M stage. (C) 2016 Elsevier Ltd. All rights reserved.