4,5-dimethyl-thiophene-2-carboxylic acid methylamide | 399043-16-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 英文名称: 4,5-dimethyl-thiophene-2-carboxylic acid methylamide
• 英文别名: N,4,5-trimethylthiophene-2-carboxamide
• CAS: 399043-16-4
• 化学式: C₈H₁₁NOS
• mdl: MFCD01578277
• 分子量: 169.247
• InChiKey: JMHSGUYUAOQLDN-UHFFFAOYSA-N

物化性质

• 沸点：
  264.3±40.0 °C(Predicted)
• 密度：
  1.114±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.375
• 拓扑面积：
  57.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4,5-dimethyl-thiophene-2-carboxylic acid methylamide 在 氢氧化钾 、 叔丁基锂 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 12.5h， 生成 4,5-Dimethyl-3-[3-(trifluoromethyl)benzoyl]thiophene-2-carboxylic acid
  参考文献：
  名称：

  2-Amino-3-aroyl-4,5-alkylthiophenes:  Agonist Allosteric Enhancers at Human A₁ Adenosine Receptors

  摘要：

  2-Amino-3-benzoylthiophenes are allosteric enhancers (AE) of agonist activity at the A(1) adenosine receptor. The present report describes syntheses and assays of the AE activity at the human A(1)AR (hA(1)AR) of a panel of compounds consisting of nine 2-amino-3-aroylthiophenes (3a-i), eight 2-amino-3-benzoyl-4,5-dimethylthiophenes (12a-h), three 3-aroyl-2-carboxy-4,5-dimethylthiophenes (15a-c), 10 2-amino-3-benzoyl-5,6-dihydro-4H-cyclopenta[b]thiophenes (17a-j), 14 2-amino-3-benzoyl-4,5,6,7-tetrahydrobenzo[b]thiophenes (18a-n), and 15 2-amino-3-benzoyl-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophenes (19a-o). An in vitro assay employing the A(1)AR agonist [I-125]ABA and membranes from CHO-K1 cells stably expressing the hA(1)AR measured, as an index of AE activity, the ability of a candidate AE to stabilize the agonist-A(1)AR-G protein ternary complex. Compounds 3a-i had little or no AE activity, and compounds 12a-h had only modest activity, evidence that AE activity depended absolutely on the presence of at least a methyl group at C-4 and C-5. Compounds 17a-c lacked AE activity, suggesting the 2-amino group is essential. Polymethylene bridges linked thiophene C-4 and C-5 of compounds 17a-j, 18a-n, and 19a-o. AE activity increased with the size of the -(CH2)(n)- bridge, n = 3 < n = 4 < n = 5. The 3-carbethoxy substituents of 17a, 18a, and 19a did not support AE activity, but a 3-aroyl group did. Bulky (or hydrophobic) substituents at the meta and para positions of the 3-benzoyl group and also 3-naphthoyl groups greatly enhanced activity. Thus, the hA(1)AR contains an allosteric binding site able to accommodate 3-aroyl substituents that are bulky and/or hydrophobic but not necessarily planar. A second region in the allosteric binding site interacts constructively with alkyl substituents at thiophene C-4 and/or C-5.

  DOI：

  10.1021/jm010081p
• 作为产物：
  描述：

  1-(4,5-二甲基-2-噻吩)乙酮 在 五氯化磷 、 盐酸羟胺 、 barium carbonate 作用下， 以 乙醚 、 乙醇 为溶剂， 反应 8.75h， 生成 4,5-dimethyl-thiophene-2-carboxylic acid methylamide
  参考文献：
  名称：

  2-Amino-3-aroyl-4,5-alkylthiophenes:  Agonist Allosteric Enhancers at Human A₁ Adenosine Receptors

  摘要：

  2-Amino-3-benzoylthiophenes are allosteric enhancers (AE) of agonist activity at the A(1) adenosine receptor. The present report describes syntheses and assays of the AE activity at the human A(1)AR (hA(1)AR) of a panel of compounds consisting of nine 2-amino-3-aroylthiophenes (3a-i), eight 2-amino-3-benzoyl-4,5-dimethylthiophenes (12a-h), three 3-aroyl-2-carboxy-4,5-dimethylthiophenes (15a-c), 10 2-amino-3-benzoyl-5,6-dihydro-4H-cyclopenta[b]thiophenes (17a-j), 14 2-amino-3-benzoyl-4,5,6,7-tetrahydrobenzo[b]thiophenes (18a-n), and 15 2-amino-3-benzoyl-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophenes (19a-o). An in vitro assay employing the A(1)AR agonist [I-125]ABA and membranes from CHO-K1 cells stably expressing the hA(1)AR measured, as an index of AE activity, the ability of a candidate AE to stabilize the agonist-A(1)AR-G protein ternary complex. Compounds 3a-i had little or no AE activity, and compounds 12a-h had only modest activity, evidence that AE activity depended absolutely on the presence of at least a methyl group at C-4 and C-5. Compounds 17a-c lacked AE activity, suggesting the 2-amino group is essential. Polymethylene bridges linked thiophene C-4 and C-5 of compounds 17a-j, 18a-n, and 19a-o. AE activity increased with the size of the -(CH2)(n)- bridge, n = 3 < n = 4 < n = 5. The 3-carbethoxy substituents of 17a, 18a, and 19a did not support AE activity, but a 3-aroyl group did. Bulky (or hydrophobic) substituents at the meta and para positions of the 3-benzoyl group and also 3-naphthoyl groups greatly enhanced activity. Thus, the hA(1)AR contains an allosteric binding site able to accommodate 3-aroyl substituents that are bulky and/or hydrophobic but not necessarily planar. A second region in the allosteric binding site interacts constructively with alkyl substituents at thiophene C-4 and/or C-5.

  DOI：

  10.1021/jm010081p

文献信息

• 2-amino-3-aroyl-4,5 alkylthiophenes: agonist allosteric enhancers at human A1 adenosine receptors
  申请人：——

  公开号：US20030078248A1

  公开（公告）日：2003-04-24

  The present invention relates to a compound of formula (I): 1 wherein: R 3 is selected from the group consisting of 1-napthyl, 2-napthyl and cycloalkylphenyl; and R 4 and R 5 taken together form a ring having from 5 to 10 carbon atoms. Additionally, the invention provides a therapeutic method for preventing or treating a pathological condition or symptom in a mammal subject, such as a human, wherein increased angiogenesis is desired, comprising administering to a mammal in need of such therapy an effective amount of the aforementioned thiophene selective adenosine A 1 allosteric enhancer.

  本发明涉及以下式（I）的化合物：其中：R3选择自1-萘基、2-萘基和环烷基苯基所组成的群；以及R4和R5一起形成含有5到10个碳原子的环。此外，本发明提供了一种治疗方法，用于预防或治疗哺乳动物主体（如人类）中的病理状况或症状，其中需要增加血管生成，包括向需要此类治疗的哺乳动物中施用上述噻吩选择性腺苷A1受体变构增强剂的有效量。
• 2-Amino-3-aroyl-4,5 alkylthiophenes: agonist allosteric enhancers at human A1 adenosine receptors
  申请人：——

  公开号：US20040180948A1

  公开（公告）日：2004-09-16

  The present invention relates to a compound of formula (I): 1 wherein: R 3 is selected from the group consisting of 1-napthyl, 2-napthyl and cycloalkylphenyl; and R 4 and R 5 taken together form a ring having from 5 to 10 carbon atoms. Additionally, the invention provides a therapeutic method for preventing or treating a pathological condition or symptom in a mammal subject, such as a human, wherein increased angiogenesis is desired, comprising administering to a mammal in need of such therapy an effective amount of the aforementioned thiophene selective adenosine A 1 allosteric enhancer.

  本发明涉及一种式（I）的化合物：1其中：R3选自1-萘基，2-萘基和环烷基苯基的群组；以及R4和R5一起形成一个具有5至10个碳原子的环。此外，本发明提供了一种治疗方法，用于预防或治疗哺乳动物受体中的病理状况或症状，例如人类，其中需要增加血管生成，包括向需要此种治疗的哺乳动物中注射上述噻吩选择性腺苷A1异构增强剂的有效剂量。
• Heterobicyclic metalloprotease inhibitors
  申请人：Hochgurtel Matthias

  公开号：US20080221083A1

  公开（公告）日：2008-09-11

  The present invention relates generally to amide containing heterobicyclic containing pharmaceutical agents, and in particular, to amide containing heterobicyclic metalloprotease inhibiting compounds. More particularly, the present invention provides a new class of heterobicyclic MMP-3 and/or MMP-13 inhibiting compounds, that exhibit an increased potency and selectivity in relation to currently known MMP-13 and MMP-3 inhibitors.
• US7019027B2
  申请人：——

  公开号：US7019027B2

  公开（公告）日：2006-03-28