(R)-2-(5-bromo-thiophene-2-sulfonylamino)-3-(1H-indol-3-yl)propionic acid | 203640-36-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (R)-2-(5-bromo-thiophene-2-sulfonylamino)-3-(1H-indol-3-yl)propionic acid
• 英文别名: (R)-2-(5-bromothiophene-2-sulfonamido)-3-(1H-indol-3-yl)propanoic acid；(R)-2-(5-Bromo-thiophene-2-sulfonylamino)-3-(1H-indol-3-yl)-propionic acid；(2R)-2-[(5-bromothiophen-2-yl)sulfonylamino]-3-(1H-indol-3-yl)propanoic acid
• CAS: 203640-36-2
• 化学式: C₁₅H₁₃BrN₂O₄S₂
• 分子量: 429.315
• InChiKey: HZSOMFPFWOJMFV-GFCCVEGCSA-N

物化性质

• 沸点：
  668.6±65.0 °C(Predicted)
• 密度：
  1.739±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  136
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (R)-2-(5-bromo-thiophene-2-sulfonylamino)-3-(1H-indol-3-yl)propionic acid 在 N-甲基吗啉 、 盐酸 、 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.67h， 生成 (2R)-2-(5-((4-butylphenyl)ethynyl)thiophene-2-sulfonamido)-N-hydroxy-3-(1H-indol-3-yl)propanamide
  参考文献：
  名称：

  Synthesis and biological evaluation in U87MG glioma cells of (ethynylthiophene)sulfonamido-based hydroxamates as matrix metalloproteinase inhibitors

  摘要：

  Matrix metalloproteinases (MMPs) are important factors in gliomas since these enzymes facilitate invasion into the surrounding brain and participate in neovascularization. In particular, the gelatinases (MMP-2 and MMP-9), and more recently MMP-25, have been shown to be highly expressed in gliomas and have been associated with disease progression. Thus, inhibition of these MMPs may represent a promising non-cytotoxic approach to glioma treatment. We report herein the synthesis and biological evaluation of a series of 4-butylphenyl(ethynylthiophene)sulfonamido-based hydroxamates. Among the new compounds tested, a promising derivative, 5a, was identified, which exhibits nanomolar inhibition of MMP-2, MMP-9, and MMP-25, but weak inhibitory activity toward other members of the MMP family. This compound also exhibited anti-invasive activity of U87MG glioblastoma cells at nanomolar concentrations, without affecting cell viability. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.03.033
• 作为产物：
  描述：

  5-溴噻吩-2-磺酰氯 、 D-色氨酸 在 sodium carbonate 作用下， 以 丙酮 为溶剂， 反应 1.75h， 以74%的产率得到(R)-2-(5-bromo-thiophene-2-sulfonylamino)-3-(1H-indol-3-yl)propionic acid
  参考文献：
  名称：

  [EN] COMPOUNDS AND METHODS FOR THE TREATMENT OF PAIN AND OTHER DISORDERS
  [FR] COMPOSÉS ET MÉTHODES DE TRAITEMENT DE LA DOULEUR ET D'AUTRES TROUBLES

  摘要：

  本发明一般涉及制药剂，特别是金属蛋白酶抑制剂化合物。更具体地说，本发明提供了一类新的双重作用MMP-2和MMP-9抑制化合物，其在与目前已知的MMP-2和MMP-9抑制剂相比，表现出增强的效力、代谢稳定性和/或降低的毒性，用于治疗疼痛和其他疾病。此外，本发明涉及一种治疗疼痛、成瘾和/或戒断症状的方法，包括向患者投予一种疼痛减轻有效量的当前化合物。

  公开号：

  WO2012118498A1

文献信息

• Compounds and methods for the treatment of pain and other diseases
  申请人：Sucholeiki Irving

  公开号：US20110230452A1

  公开（公告）日：2011-09-22

  The present invention relates generally to pharmaceutical agents, and in particular, to metalloprotease inhibitor compounds. More particularly, the present invention provides a new class of dual acting MMP-2 and MMP-9 inhibiting compounds that exhibit increased potency, metabolic stability and/or reduced toxicity in relation to currently known MMP-2 and MMP-9 inhibitors for the treatment of pain and other diseases. Additionally, the present invention relates to methods for treating pain, addiction and/or withdrawal symptoms in a patient comprising administering to the patient a pain-reducing effective amount of a present compound.

  本发明通常涉及制药剂，特别是金属蛋白酶抑制剂化合物。更具体地，本发明提供了一类新的双重作用MMP-2和MMP-9抑制化合物，这些化合物在与目前已知的MMP-2和MMP-9抑制剂相比具有增强的效力、代谢稳定性和/或降低的毒性，用于治疗疼痛和其他疾病。此外，本发明涉及一种治疗疼痛、成瘾和/或戒断症状的方法，包括向患者施用一定量的具有减轻疼痛作用的本发明化合物。
• [EN] COMPOUNDS AND METHODS FOR THE TREATMENT OF DEGENERATIVE DISORDERS<br/>[FR] COMPOSÉS ET MÉTHODES DE TRAITEMENT DE MALADIES DÉGÉNÉRATIVES
  申请人：AQUILUS PHARMACEUTICALS INC

  公开号：WO2020154243A1

  公开（公告）日：2020-07-30

  The present disclosure relates generally to alkyne containing pharmaceutical agents, and in particular, to phenylethynyl-thiophene based compounds. More particularly, the present disclosure provides a class of compounds that can inhibit and/or attenuate apoptosis via caspase 3 for the treatment of various degenerative disorders. Additionally, the present disclosure relates to methods for treating specific degenerative disorders such as amyotrophic lateral sclerosis (ALS), Huntington's disease, epilepsy, spinal cord injury, complication due to diabetes, multiple sclerosis (MS), muscular dystrophy (MD), Parkinson's disease (PD), irritable bowel syndrome (IBS) and Alzheimer's disease (AD) in a patient comprising administering to the patient an effective amount of a present compound.

  本公开涉及含炔基的药物代理，特别是基于苯基乙炔基噻吩的化合物。更具体地说，本公开提供了一类化合物，可以通过卡斯帕赛3抑制和/或减轻细胞凋亡，用于治疗各种退行性疾病。此外，本公开还涉及治疗特定退行性疾病的方法，例如肌萎缩侧索硬化症（ALS）、亨廷顿病、癫痫、脊髓损伤、糖尿病并发症、多发性硬化症（MS）、肌萎缩症（MD）、帕金森病（PD）、肠易激综合征（IBS）和阿尔茨海默病（AD），包括向患者施用本发明化合物的有效量。
• [EN] COMPOUNDS AND METHODS FOR THE TREATMENT OF PAIN AND OTHER DISORDERS<br/>[FR] COMPOSÉS ET MÉTHODES DE TRAITEMENT DE LA DOULEUR ET D'AUTRES TROUBLES
  申请人：SUCHOLEIKI IRVING

  公开号：WO2012118498A1

  公开（公告）日：2012-09-07

  The present invention relates generally to pharmaceutical agents, and in particular, to metalloprotease inhibitor compounds. More particularly, the present invention provides a new class of dual acting MMP-2 and MMP-9 inhibiting compounds that exhibit increased potency, metabolic stability and/or reduced toxicity in relation to currently known MMP-2 and MMP-9 inhibitors for the treatment of pain and other diseases. Additionally, the present invention relates to methods for treating pain, addiction and/or withdrawal symptoms in a patient comprising administering to the patient a pain-reducing effective amount of a present compound.

  本发明一般涉及制药剂，特别是金属蛋白酶抑制剂化合物。更具体地说，本发明提供了一类新的双重作用MMP-2和MMP-9抑制化合物，其在与目前已知的MMP-2和MMP-9抑制剂相比，表现出增强的效力、代谢稳定性和/或降低的毒性，用于治疗疼痛和其他疾病。此外，本发明涉及一种治疗疼痛、成瘾和/或戒断症状的方法，包括向患者投予一种疼痛减轻有效量的当前化合物。
• COMPOUNDS AND METHODS FOR THE TREATMENT OF PAIN AND OTHER DISEASES
  申请人：Sucholeiki Irving

  公开号：US20110257222A1

  公开（公告）日：2011-10-20

  The present invention relates generally to alkyne containing pharmaceutical agents, and in particular, to phenylethynyl-thiophene based metalloprotease inhibitor compounds. More particularly, the present invention provides a new class of MMP inhibiting compounds that exhibit increased potency, metabolic stability and/or reduced toxicity in relation to currently known MMP inhibitors for the treatment of pain and other diseases such as cancer. Additionally, the present invention relates to methods for treating pain in a patient comprising administering to the patient a pain-reducing effective amount of a present compound.

  本发明通常涉及含炔基的药物，特别是基于苯基乙炔基硫苯基的金属蛋白酶抑制剂化合物。更具体地说，本发明提供了一种新型MMP抑制剂化合物，其在治疗疼痛和其他疾病（如癌症）方面表现出增强的效力、代谢稳定性和/或降低的毒性，相对于目前已知的MMP抑制剂。此外，本发明还涉及治疗患者疼痛的方法，包括向患者施用一种当前化合物的减痛有效量。
• [EN] COMPOUNDS AND METHODS FOR THE TREATMENT OF PAIN AND OTHER DISEASES<br/>[FR] COMPOSÉS ET PROCÉDÉS POUR LE TRAITEMENT DE LA DOULEUR ET D'AUTRES MALADIES
  申请人：AQUILUS PHARMACEUTICALS INC

  公开号：WO2010075287A3

  公开（公告）日：2010-10-28