3-Amino-4-(propan-2-yloxy)benzoic acid

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-Amino-4-(propan-2-yloxy)benzoic acid
• 英文别名: 3-amino-4-propan-2-yloxybenzoic acid
• 化学式: C₁₀H₁₃NO₃
• mdl: MFCD12771614
• 分子量: 195.218
• InChiKey: YIAGHMRDAHWMKF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 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：

  3-Amino-4-(propan-2-yloxy)benzoic acid 在 氯化亚砜 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 生成 methyl 3-benzamido-4-propan-2-yloxybenzoate
  参考文献：
  名称：

  Structure-Based Design and Synthesis of Novel Inhibitors Targeting HDAC8 from Schistosoma mansoni for the Treatment of Schistosomiasis

  摘要：

  Schistosomiasis is a major neglected parasitic disease that affects more than 265 million people worldwide and for which the control strategy consists of mass treatment with the only available drug, praziquantel. In this study, a series of new benzohydroxamates were prepared as potent inhibitors of Schistosoma mansoni histone deacetylase 8 (smHDAC8). Crystallographic analysis provided insights into the: inhibition mode of smHDAC8 activity by these 3-amidobenzohydroxamates. The newly designed inhibitors were evaluated in screens for enzyme inhibitory activity against schistosome and human HDACs. Twenty-seven compounds were found to be active in the nanomolar range, and some of them showed selectivity toward smHDAC8 over the major human HDACs (I and 6). The active benzohydroxamates were additionally screened for lethality against the schistosome larval stage using a fluorescence-based assay. Four of these showed significant dose-dependent killing of the schistosome larvae and markedly impaired egg laying of adult worm pairs maintained in culture.

  DOI：

  10.1021/acs.jmedchem.5b01478

文献信息

• S1P1 AGONIST AND APPLICATION THEREOF
  申请人：Shijiazhuang Sagacity New Drug Development Co., Ltd.

  公开号：EP3492465A1

  公开（公告）日：2019-06-05

  The present invention relates to a class of tricyclic compounds and an application thereof as a sphingosine 1-phosphate type 1 (S1P1) receptor agonist. The invention specifically relates to a compound represented by formula (II), and a tautomer and pharmaceutically acceptable salt of same.

  本发明涉及一类三环化合物及其作为 1 型鞘磷脂（S1P1）受体激动剂的应用。本发明具体涉及由式（II）代表的化合物及其同系物和药学上可接受的盐。
• Concurrent Optimizations of Efficacy and Blood–Brain Barrier Permeability in New Macrocyclic LRRK2 Inhibitors for Potential Parkinson’s Disease Therapeutics
  作者：Kewon Kim、Ahyoung Jang、Hochul Shin、Inhae Ye、Ji Eun Lee、Taeho Kim、Hwangseo Park、Sungwoo Hong

  DOI：10.1021/acs.jmedchem.4c00520

  日期：——

  quest for effective LRRK2 inhibitors has been impeded by the formidable challenge of crossing the blood–brain barrier (BBB). We leveraged structure-based de novo design and developed robust three-dimensional quantitative structure–activity relationship (3D-QSAR) models to predict BBB permeability, enhancing the likelihood of the inhibitor’s brain accessibility. Our strategy involved the synthesis of macrocyclic

  富含亮氨酸重复激酶 2 (LRRK2) 活性升高与帕金森病 (PD) 的发病机制有关。跨越血脑屏障（BBB）的巨大挑战阻碍了对有效 LRRK2 抑制剂的探索。我们利用基于结构的从头设计，开发了稳健的三维定量结构-活性关系 (3D-QSAR) 模型来预测 BBB 通透性，从而提高抑制剂进入大脑的可能性。我们的策略涉及通过将 HG-10-102-01 的两个末端氮原子与 2 至 4 个单元的烷基链连接来合成大环分子，为创新的 LRRK2 抑制剂设计奠定基础。通过对生化功效和血脑屏障渗透性进行细致的计算和合成优化，14 种合成候选物中的 9 种表现出有效的低纳摩尔抑制和显着的血脑屏障渗透性。对体外和体内有效性的进一步评估以及药理学分析表明8是有前途的 PD 治疗新先导化合物。
• Indole derivatives as S1P1 receptor agonists
  申请人：Glaxo Group Limited

  公开号：EP2206710B1

  公开（公告）日：2012-07-04
• SPIRO COMPOUND AND USE THEREOF
  申请人：Medshine Discovery Inc.

  公开号：EP3590929B1

  公开（公告）日：2021-09-15
• Structure-Based Design and Synthesis of Novel Inhibitors Targeting HDAC8 from <i>Schistosoma mansoni</i> for the Treatment of Schistosomiasis
  作者：Tino Heimburg、Alokta Chakrabarti、Julien Lancelot、Martin Marek、Jelena Melesina、Alexander-Thomas Hauser、Tajith B. Shaik、Sylvie Duclaud、Dina Robaa、Frank Erdmann、Matthias Schmidt、Christophe Romier、Raymond J. Pierce、Manfred Jung、Wolfgang Sippl

  DOI：10.1021/acs.jmedchem.5b01478

  日期：2016.3.24

  Schistosomiasis is a major neglected parasitic disease that affects more than 265 million people worldwide and for which the control strategy consists of mass treatment with the only available drug, praziquantel. In this study, a series of new benzohydroxamates were prepared as potent inhibitors of Schistosoma mansoni histone deacetylase 8 (smHDAC8). Crystallographic analysis provided insights into the: inhibition mode of smHDAC8 activity by these 3-amidobenzohydroxamates. The newly designed inhibitors were evaluated in screens for enzyme inhibitory activity against schistosome and human HDACs. Twenty-seven compounds were found to be active in the nanomolar range, and some of them showed selectivity toward smHDAC8 over the major human HDACs (I and 6). The active benzohydroxamates were additionally screened for lethality against the schistosome larval stage using a fluorescence-based assay. Four of these showed significant dose-dependent killing of the schistosome larvae and markedly impaired egg laying of adult worm pairs maintained in culture.