2-methylbenzothiophene-3-carboxylic acid chloride | 17375-83-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻吩类
• 英文名称: 2-methylbenzothiophene-3-carboxylic acid chloride
• 英文别名: 3-Chlorcarbonyl-2-methyl-benzothiophen；2-methyl-benzo[b]thiophene-3-carbonyl chloride；2-Methylbenzo[b]thiophene-3-carbonyl chloride；2-methyl-1-benzothiophene-3-carbonyl chloride
• CAS: 17375-83-6
• 化学式: C₁₀H₇ClOS
• 分子量: 210.684
• InChiKey: SNBWUNMFYNJTSL-UHFFFAOYSA-N

物化性质

• 沸点：
  324.6±22.0 °C(Predicted)
• 密度：
  1.353±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  45.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-methylbenzothiophene-3-carboxylic acid chloride 在 2,6-二甲基吡啶 、 N-氯代丁二酰亚胺 、 三甲基铝 、 过氧化苯甲酰 作用下， 以 1,4-二氧六环 、 四氯化碳 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 2-[4-methoxy-3-[2-(4-methylpiperidin-1-yl)ethoxy]phenyl]-3H-[1]benzothiolo[2,3-c]pyrrol-1-one
  参考文献：
  名称：

  5-HT2C antagonists based on fused heterotricyclic templates: Design, synthesis and biological evaluation

  摘要：

  Design, synthesis and properties of a new tricyclic series of selective 5-HT2C receptor antagonists are reported. Conformational analysis of a 2-phenyl-dihydropyrrolone scaffold suggested that ring fusion, locking coplanarity between the rings of this moiety, might be tolerated by the 5-HT2C receptor. An interesting effect of this is the change of the nature of the carbon-carbon double bond of the lactam ring from vinylic to aromatic. The changes were found to result in a favourable profile at both, receptor and in vivo level. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.10.034
• 作为产物：
  描述：

  2-methylbenzo[b]thiophene-3-carboxylic acid 在 氯化亚砜 、 N,N-二甲基甲酰胺 作用下， 以 甲苯 为溶剂， 反应 2.0h， 生成 2-methylbenzothiophene-3-carboxylic acid chloride
  参考文献：
  名称：

  2-(Quinuclidin-3-yl)pyrido[4,3-b]indol-1-ones and isoquinolin-1-ones. Potent conformationally restricted 5-HT3 receptor antagonists

  摘要：

  Several series of N-(quinuclidin-3-yl)aryl and heteroaryl-fused pyridones were synthesized and evaluated for 5-HT3 receptor affinity. In the heteroaryl series, 2-(quinuclidin-3-yl)tetrahydropyrido-[4,3-b]indol-1-one (8a) and the 4,5-alkano-bridged analogues (14 and 15) displayed high 5-HT3 receptor affinity with pK(i) values > 9. The (3S)-quinuclidinyl isomers had > 10 fold higher affinity than the (3R)-isomers. In a series of 2-quinuclidin-3-yl)isoquinolin-1-ones, derivatives substituted with small lipophilic groups (25b-e) and with 4,5-alkano-bridges (34-36) also displayed high affinity. In particular, the hexahydro-1H-benz[de]isoquinolinone (S,S)-37 was the highest affinity 5-HT3 receptor ligand prepared (pK(i) 10.4). A number of the high affinity ligands were shown to be potent 5-HT3 receptor antagonists in vivo as determined by inhibition of the B-J reflex in the anesthetized rat. Again, (S,S)-37 was the most active agent tested (ID50 0.02 mug/kg iv), and this compound was also potent in blocking cisplatin-induced emesis in both the ferret and the dog. Computer modeling studies were performed, and previously reported 5-HT3 receptor antagonist pharmacophore models were refined to include a key lipophilic binding domain.

  DOI：

  10.1021/jm00070a008

文献信息

• 2-(Quinuclidin-3-yl)pyrido[4,3-b]indol-1-ones and isoquinolin-1-ones. Potent conformationally restricted 5-HT3 receptor antagonists
  作者：Robin D. Clark、Aaron B. Miller、Jacob Berger、David B. Repke、Klaus K. Weinhardt、Bruce A. Kowalczyk、Richard M. Eglen、Douglas W. Bonhaus、Chi Ho Lee

  DOI：10.1021/jm00070a008

  日期：1993.9

  Several series of N-(quinuclidin-3-yl)aryl and heteroaryl-fused pyridones were synthesized and evaluated for 5-HT3 receptor affinity. In the heteroaryl series, 2-(quinuclidin-3-yl)tetrahydropyrido-[4,3-b]indol-1-one (8a) and the 4,5-alkano-bridged analogues (14 and 15) displayed high 5-HT3 receptor affinity with pK(i) values > 9. The (3S)-quinuclidinyl isomers had > 10 fold higher affinity than the (3R)-isomers. In a series of 2-quinuclidin-3-yl)isoquinolin-1-ones, derivatives substituted with small lipophilic groups (25b-e) and with 4,5-alkano-bridges (34-36) also displayed high affinity. In particular, the hexahydro-1H-benz[de]isoquinolinone (S,S)-37 was the highest affinity 5-HT3 receptor ligand prepared (pK(i) 10.4). A number of the high affinity ligands were shown to be potent 5-HT3 receptor antagonists in vivo as determined by inhibition of the B-J reflex in the anesthetized rat. Again, (S,S)-37 was the most active agent tested (ID50 0.02 mug/kg iv), and this compound was also potent in blocking cisplatin-induced emesis in both the ferret and the dog. Computer modeling studies were performed, and previously reported 5-HT3 receptor antagonist pharmacophore models were refined to include a key lipophilic binding domain.
• 5-HT2C antagonists based on fused heterotricyclic templates: Design, synthesis and biological evaluation
  作者：Dieter Hamprecht、Fabrizio Micheli、Giovanna Tedesco、Daniele Donati、Marcella Petrone、Silvia Terreni、Martyn Wood

  DOI：10.1016/j.bmcl.2006.10.034

  日期：2007.1

  Design, synthesis and properties of a new tricyclic series of selective 5-HT2C receptor antagonists are reported. Conformational analysis of a 2-phenyl-dihydropyrrolone scaffold suggested that ring fusion, locking coplanarity between the rings of this moiety, might be tolerated by the 5-HT2C receptor. An interesting effect of this is the change of the nature of the carbon-carbon double bond of the lactam ring from vinylic to aromatic. The changes were found to result in a favourable profile at both, receptor and in vivo level. (c) 2006 Elsevier Ltd. All rights reserved.