5-(氨基甲基)-3-噻吩羧酸 | 503469-38-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 中文名称: 5-(氨基甲基)-3-噻吩羧酸
• 英文名称: 5-aminomethyl-thiophene-3-carboxylic acid
• 英文别名: 5-(Aminomethyl)thiophene-3-carboxylic acid
• CAS: 503469-38-3
• 化学式: C₆H₇NO₂S
• 分子量: 157.193
• InChiKey: CGZIAHDHOVMWQN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.3
• 重原子数：
  10
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  91.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  9-芴甲基-N-琥珀酰亚胺基碳酸酯 、 5-(氨基甲基)-3-噻吩羧酸 在 碳酸氢钠 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 3.0h， 生成 5[(9H-fluoren-9-ylmethoxycarbonylamino)methyl]-thiophene-3-carboxylic acid
  参考文献：
  名称：

  Identification of Potent and Selective Small-Molecule Inhibitors of Caspase-3 through the Use of Extended Tethering and Structure-Based Drug Design

  摘要：

  The design, synthesis, and in vitro activities of a series of potent and selective small-molecule inhibitors of caspase-3 are described. From extended tethering, a salicylic acid fragment was identified as having binding affinity for the S-4 pocket of caspase-3. X-ray crystallography and molecular modeling of the initial tethering hit resulted in the synthesis of 4, which reversibly inhibited caspase-3 with a K-i = 40 nM. Further optimization led to the identification of a series of potent and selective inhibitors with K-i values in the 20-50 nM range. One of the most potent compounds in this series, 66b, inhibited caspase-3 with a K-i = 20 nM and selectivity of 8-500-fold for caspase-3 vs a panel of seven caspases (1, 2, and 4-8). A high-resolution X-ray cocrystal structure of 4 and 66b supports the predicted binding modes of our compounds with caspase-3.

  DOI：

  10.1021/jm020230j
• 作为产物：
  描述：

  ((4-bromothiophene-2-yl)methoxy)(tert-butyl)dimethylsilane 在 palladium on activated charcoal lithium hydroxide 、 正丁基锂 、 sodium azide 、 四溴化碳 、 四丁基氟化铵 、 氢气 、 溶剂黄146 、 三苯基膦 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 正己烷 、 N,N-二甲基甲酰胺 为溶剂， -78.0~50.0 ℃ 、206.84 kPa 条件下， 反应 18.5h， 生成 5-(氨基甲基)-3-噻吩羧酸
  参考文献：
  名称：

  Identification of Potent and Selective Small-Molecule Inhibitors of Caspase-3 through the Use of Extended Tethering and Structure-Based Drug Design

  摘要：

  The design, synthesis, and in vitro activities of a series of potent and selective small-molecule inhibitors of caspase-3 are described. From extended tethering, a salicylic acid fragment was identified as having binding affinity for the S-4 pocket of caspase-3. X-ray crystallography and molecular modeling of the initial tethering hit resulted in the synthesis of 4, which reversibly inhibited caspase-3 with a K-i = 40 nM. Further optimization led to the identification of a series of potent and selective inhibitors with K-i values in the 20-50 nM range. One of the most potent compounds in this series, 66b, inhibited caspase-3 with a K-i = 20 nM and selectivity of 8-500-fold for caspase-3 vs a panel of seven caspases (1, 2, and 4-8). A high-resolution X-ray cocrystal structure of 4 and 66b supports the predicted binding modes of our compounds with caspase-3.

  DOI：

  10.1021/jm020230j

文献信息

• INACTIVATORS OF TOXOPLASMA GONDII ORNITHINE AMINOTRANSFERASE FOR TREATING TOXOPLASMOSIS AND MALARIA
  申请人：Northwestern University

  公开号：US20180098952A1

  公开（公告）日：2018-04-12

  Disclosed are methods, compounds, and compositions for treating infection by an Apicomplexan parasite that include administering a compound that selectively inactivates ornithine aminotransferase of the Apicomplexan parasite. Specifically, the methods, compounds, compounds may be utilized for treating infection by Toxoplasma gondii and toxoplasmosis and for treating infection by Plasmodium falciparum and malaria. The compounds disclosed herein are observed to selectively inactivate Toxoplasma gondii ornithine aminotransferase (TgOAT) relative to human OAT and relative to human γ-aminobutyric aminotransferase (GABA-AT).

  揭示了一种治疗具有选择性灭活裂殖孢子虫的鸟氨基转移酶的化合物、方法和组合物。具体来说，这些方法、化合物可用于治疗弓形虫和弓形虫病感染，以及治疗疟原虫和疟疾感染。本文披露的化合物被观察到相对于人类鸟氨基转移酶和人类γ-氨基丁酸氨基转移酶（GABA-AT）具有选择性地灭活弓形虫鸟氨基转移酶（TgOAT）。
• 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。
• Inactivators of Toxoplasma gondii ornithine aminotransferase for treating toxoplasmosis and malaria
  申请人：Northwestern University

  公开号：US10632088B2

  公开（公告）日：2020-04-28

  Disclosed are methods, compounds, and compositions for treating infection by an Apicomplexan parasite that include administering a compound that selectively inactivates ornithine aminotransferase of the Apicomplexan parasite. Specifically, the methods, compounds, compounds may be utilized for treating infection by Toxoplasma gondii and toxoplasmosis and for treating infection by Plasmodium falciparum and malaria. The compounds disclosed herein are observed to selectively inactivate Toxoplasma gondii ornithine aminotransferase (TgOAT) relative to human OAT and relative to human γ-aminobutyric aminotransferase (GABA-AT).

  本发明公开了治疗弓形虫感染的方法、化合物和组合物，其中包括施用选择性灭活弓形虫鸟氨酸氨基转移酶的化合物。具体来说，这些方法、化合物可用于治疗弓形虫感染和弓形虫病，以及恶性疟原虫感染和疟疾。据观察，相对于人类鸟氨酸氨基转移酶（OAT）和人类γ-氨基丁酸氨基转移酶（GABA-AT），本文公开的化合物可选择性地灭活弓形虫鸟氨酸氨基转移酶（TgOAT）。
• Inactivators of toxoplasma gondii ornithine aminotransferase for treating toxoplasmosis and malaria
  申请人：Northwestern University

  公开号：US11207283B2

  公开（公告）日：2021-12-28

  Disclosed are methods, compounds, and compositions for treating infection by an Apicomplexan parasite that include administering a compound that selectively inactivates ornithine aminotransferase of the Apicomplexan parasite. Specifically, the methods, compounds, compounds may be utilized for treating infection by Toxoplasma gondii and toxoplasmosis and for treating infection by Plasmodium falciparum and malaria. The compounds disclosed herein are observed to selectively inactivate Toxoplasma gondii ornithine aminotransferase (TgOAT) relative to human OAT and relative to human γ-aminobutyric aminotransferase (GABA-AT).

  本发明公开了治疗弓形虫感染的方法、化合物和组合物，其中包括施用选择性灭活弓形虫鸟氨酸氨基转移酶的化合物。具体来说，这些方法、化合物可用于治疗弓形虫感染和弓形虫病，以及恶性疟原虫感染和疟疾。据观察，相对于人类鸟氨酸氨基转移酶（OAT）和人类γ-氨基丁酸氨基转移酶（GABA-AT），本文公开的化合物可选择性地灭活弓形虫鸟氨酸氨基转移酶（TgOAT）。
• SPIRO-HYDANTOIN COMPOUNDS USEFUL AS ANTI-INFLAMMATORY AGENTS
  申请人：Bristol-Myers Squibb Company

  公开号：EP1432700B1

  公开（公告）日：2009-11-04