2-[3-(氨基甲基)苯氧基]乙酸 | 115464-36-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2-[3-(氨基甲基)苯氧基]乙酸
• 英文名称: 2-(3-(aminomethyl)phenoxy) acetic acid
• 英文别名: 2-[3-(Azaniumylmethyl)phenoxy]acetate
• CAS: 115464-36-3
• 化学式: C₉H₁₁NO₃
• mdl: MFCD11587786
• 分子量: 181.191
• InChiKey: IGWUVOUCIOITSX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.222
• 拓扑面积：
  72.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-[3-(氨基甲基)苯氧基]乙酸 、 Boc-L-Phe-L-His-(3S,4S)-Sta-L-Leu-OCH3 生成 2-[3-[[[(2S)-2-[[(3S,4S)-3-hydroxy-4-[[(2S)-3-(1H-imidazol-5-yl)-2-[[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropanoyl]amino]propanoyl]amino]-6-methylheptanoyl]amino]-4-methylpentanoyl]amino]methyl]phenoxy]acetic acid
  参考文献：
  名称：

  Renin inhibitors containing hydrophilic groups. Tetrapeptides with enhanced aqueous solubility and nanomolar potency

  摘要：

  Nineteen tetrapeptides containing statine (Sta) and 4-amino-5-cyclohexyl-3-hydroxypentanoic acid (ACHPA) were prepared. Solubility measurements of these compounds were carried out in H2O and in pH 7.4 phosphate buffer solution, and their partition coefficients were determined in a 1:1 1-octanol/sodium phosphate-citric acid buffer system. The tetrapeptides were tested in vitro for their ability to inhibit porcine, canine, and human plasma renins. Four compounds, 6, 12, 14, and 20, were potent inhibitors against all renins tested (IC50 = 10(-9) M). Compound 12 was administered orally to dogs and substantially inhibited plasma renin activity for up to 5 h. The addition of polar groups to the C-terminus of Sta- and ACHPA-containing tetrapeptides renders them soluble in aqueous milieu and provides a valuable tool with which to examine the role of the renin-angiotensin system in physiological and pathological circumstances.

  DOI：

  10.1021/jm00118a009
• 作为产物：
  描述：

  (3-氰基苯氧基)乙酸乙酯 在 5%-palladium/activated carbon 、 氢气 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 、 溶剂黄146 为溶剂， 反应 5.0h， 生成 2-[3-(氨基甲基)苯氧基]乙酸
  参考文献：
  名称：

  A Comparative Assessment Study of Known Small-Molecule Keap1−Nrf2 Protein–Protein Interaction Inhibitors: Chemical Synthesis, Binding Properties, and Cellular Activity

  摘要：

  Inhibiting the protein-protein interaction (PPI) between the transcription factor Nrf2 and its repressor protein Keap1 has emerged as a promising strategy to target oxidative stress in diseases, including central nervous system (CNS) disorders. Numerous non-covalent small-molecule Keap1-Nrf2 PPI inhibitors have been reported to date, but many feature suboptimal physicochemical properties for permeating the blood brain barrier, while others contain problematic structural moieties. Here, we present the first side-by-side assessment of all reported Keap1-Nrf2 PPI inhibitor classes using fluorescence polarization, thermal shift assay, and surface plasmon resonance-and further evaluate the compounds in an NQO1 induction cell assay and in counter tests for nonspecific activities. Surprisingly, half of the compounds were inactive or deviated substantially from reported activities, while we confirm the cross-assay activities for others. Through this study, we have identified the most promising Keap1-Nrf2 inhibitors that can serve as pharmacological probes or starting points for developing CNS-active Keap1 inhibitors.

  DOI：

  10.1021/acs.jmedchem.9b00723

文献信息

• [EN] BENZOPYRANE AND IMIDAZOLE DERIVATIVES USEFUL FOR THE STABILIZATION OF AMYLOIDOGENIC IMMUNOGLOBULIN LIGHT CHAINS<br/>[FR] DÉRIVÉS DE STABILISATION DE BENZOPYRANE ET D'IMIDAZOLE UTILISÉS POUR LA STABILISATION DE CHAÎNES LÉGÈRES D'IMMUNOGLOBULINES AMYLOÏDOGÉNIQUES
  申请人：SCRIPPS RESEARCH INST

  公开号：WO2020205683A1

  公开（公告）日：2020-10-08

  In immunoglobulin light chain amyloidosis (AL), the unique antibody light chain (LC) protein that is secreted by monoclonal plasma cells in each patient misfolds and/or aggregates, a process leading to organ degeneration. For treating AL patients, such as those with substantial cardiac involvement who have difficulty tolerating existing chemotherapy regimens, provided herein are small molecule compounds of Formula Ia, Formula Ib, and Formula II that are kinetic stabilizers of the native dimeric structure of full-length LCs, which compounds can slow or stop the amyloidogenicity cascade at its origin.

  在免疫球蛋白轻链淀粉样变性（AL）中，每位患者体内由单克隆浆细胞分泌的独特抗体轻链（LC）蛋白会错误折叠和/或聚集，导致器官退化的过程。为了治疗AL患者，例如那些存在严重心脏受累且难以耐受现有化疗方案的患者，本文提供了化学式Ia、化学式Ib和化学式II的小分子化合物，这些化合物是全长LC的动力学稳定剂，可以减缓或停止淀粉样生成性级联反应的起源。
• Design, synthesis, and evaluation of potent novel peroxisome proliferator-activated receptor γ indole partial agonists
  作者：Venkateswararao Eeda、Dan Wu、Hui-Ying Lim、Weidong Wang

  DOI：10.1016/j.bmcl.2019.126664

  日期：2019.11

  Peroxisome Proliferator-Activated Receptor γ (PPARγ) is a nuclear receptor important for glucose homeostasis and insulin sensitivity. The anti-diabetic drugs thiazolidinediones improve insulin sensitivity by blocking PPARγ phosphorylation at S273; however, their full agonism on PPARγ also causes significant unwanted side effects. The indole derivative UHC1 displays insulin-sensitizing effect by acting

  过氧化物酶体增殖物激活受体γ（PPARγ）是一种核受体，对葡萄糖稳态和胰岛素敏感性很重要。抗糖尿病药物噻唑烷二酮可通过阻止S273处的PPARγ磷酸化来提高胰岛素敏感性。然而，它们对PPARγ的完全激动作用也会引起明显的不良副作用。吲哚衍生物UHC1通过抑制PPARγS273磷酸化而充当部分激动剂，从而显示出胰岛素增敏作用，但没有完全的激动剂相关副作用。但是，它的效能还有很多不足之处。在这里，我们通过结构-活性关系研究报告了作为部分PPARγ激动剂的有效吲哚类似物的设计和合成。
• Discovery of β-aminoacyl containing thiazolidine derivatives as potent and selective dipeptidyl peptidase IV inhibitors
  作者：Woul Seong Park、Seung Kyu Kang、Mi Ae Jun、Mi Sik Shin、Ki Young Kim、Sang Dal Rhee、Myung Ae Bae、Min Sun Kim、Kwang Rok Kim、Nam Sook Kang、Sung-eun Yoo、Jie Oh Lee、Dong Hyun Song、Peter Silinski、Stephen Edward Schneider、Jin Hee Ahn、Sung Soo Kim

  DOI：10.1016/j.bmcl.2011.01.041

  日期：2011.3

  containing thiazolidine derivatives was synthesized and evaluated for their ability to inhibit DPP-IV. Several thiazolidine derivatives with an acid moiety were found to be potent DPP-IV inhibitors. Among them, compound 2da is the most active in this series with an IC50 value of 1 nM, and it showed excellent selectivity over DPP-IV related enzymes including DPP-2, DPP-8, and DPP-9. Compound 2da is chemically

  合成了一系列含有β-氨基酰基的噻唑烷衍生物，并评估了它们抑制DPP-IV的能力。发现具有酸部分的几种噻唑烷衍生物是有效的DPP-IV抑制剂。其中，化合物2da是该系列中活性最高的化合物，IC 50值为1 nM，与DPP-IV相关的酶（包括DPP-2，DPP-8和DPP-9）相比，具有出色的选择性。化合物2da具有化学和代谢稳定性，未显示CYP抑制，hERG结合或细胞毒性。化合物2db（2da的酯类前药）在大鼠和狗模型中口服后显示出良好的体内DPP-IV抑制作用。
• SULFONAMIDE COMPOUND OR SALT THEREOF
  申请人：Astellas Pharma Inc.

  公开号：EP2050446A1

  公开（公告）日：2009-04-22

  Abstract: Disclosed is a sulfonamide compound having a chemical structure characterized in that the compound has an amide structure wherein a carbon atom in the amide binds to a nitrogen atom in a sulfonamide through a lower alkylene, or a salt of the compound. The compound or the salt has a potent antagonistic activity against an EP 1 receptor and is therefore useful as a therapeutic agent for a disease associated with an EP1 receptor, particularly lower urinary tract symptom.

  摘要：公开了一种磺酰胺化合物，其化学结构特征在于该化合物具有酰胺结构，其中酰胺中的碳原子通过低级亚烷基与磺酰胺中的氮原子结合，或该化合物的盐。该化合物或其盐对 EP1 受体具有强效拮抗活性，因此可用作与 EP1 受体相关的疾病，特别是下尿路症状的治疗剂。
• Tetrahydroisoquinolin-1-one derivative or salt thereof
  申请人：Seldar Pharma Inc.

  公开号：US10016410B2

  公开（公告）日：2018-07-10

  To provide a pharmaceutical, in particular a compound which can be used as a therapeutic agent for irritable bowel syndrome (IBS). It was found that a tetrahydroisoquinolin-1-one derivative having an amide group at the 4-position or a pharmaceutically acceptable salt thereof has an excellent bombesin 2 (BB2) receptor antagonistic action. It is also found that the tetrahydroisoquinolin-1-one derivative is highly effective on bowel movement disorders. From the above, the tetrahydroisoquinolin-1-one derivative of the present invention is useful as a therapeutic agent for diseases associated with a BB2 receptor, in particular IBS.

  提供一种药物，特别是一种可用作肠易激综合征（IBS）治疗剂的化合物。研究发现，一种在 4 位具有酰胺基团的四氢异喹啉-1-酮衍生物或其药学上可接受的盐具有很好的蚕豆素 2（BB2）受体拮抗作用。研究还发现，四氢异喹啉-1-酮衍生物对肠道运动障碍也有很好的疗效。综上所述，本发明的四氢异喹啉-1-酮衍生物可作为一种治疗剂，用于治疗与 BB2 受体相关的疾病，特别是肠易激综合征。