4-chloro-2-(3'-thienylcarbonyl)aniline | 80517-38-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-chloro-2-(3'-thienylcarbonyl)aniline
• 英文别名: (2-Amino-5-chlorophenyl)-thiophen-3-ylmethanone
• CAS: 80517-38-0
• 化学式: C₁₁H₈ClNOS
• 分子量: 237.71
• InChiKey: HWGKEBNARZBZKF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  71.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-chloro-2-(3'-thienylcarbonyl)aniline 在 lithium aluminium tetrahydride 、 三氯化铝 、 碳酸氢钠 作用下， 生成 4-Chloro-2-(thiophen-3-ylmethyl)aniline
  参考文献：
  名称：

  Hunziker; Fischer; Kipfer, European Journal of Medicinal Chemistry, 1981, vol. 16, # 5, p. 391 - 398

  摘要：

  DOI：
• 作为产物：
  描述：

  4'-氯代新戊酰苯胺 在 sodium hydroxide 、 重铬酸吡啶 、 正丁基锂 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 11.0h， 生成 4-chloro-2-(3'-thienylcarbonyl)aniline
  参考文献：
  名称：

  Syntheses of 5-thienyl and 5-furyl-substituted benzodiazepines: probes of the pharmacophore for benzodiazepine receptor agonists

  摘要：

  The synthesis of 5-thienyl- and 5-furyl-substituted benzodiazepines is described. These compounds were employed to probe the lipophilic pocket (L(3)) of the benzodiazepine receptor (BzR) and to determine the effect of occupation of L(3) on biological activity. Of the new analogs synthesized, the 5-(2-thienyl)-benzodiazepines 6a and 7a displayed high affinity for the BzR (IC50 28 and 18 nM, respectively) and exhibited both anticonvulsant (ED(50) approximate to 9 and 3 mg/kg) and muscle relaxant (ED(50) approximate to 10 and 7 mg/kg) activity. The 5-(3-thienyl)benzodiazepines 6d and 7d displayed only moderate affinity for the BzR (IC50 140 and 110 nM) and exhibited no biological activity (no anticonvulsant or muscle relaxant activity) at doses up to 40 mg/kg. The 5-(2-furyl)benzodiazepines (6b, 7b, 19b and 20b) exhibit low affinities for the BzR. These in vitro and in vivo findings are consistent with our model suggesting that pocket L(3) is very sensitive to lipophilic effects. Thus, decreasing the lipophilicity of functional groups which occupy this region decreases ligand affinity at BzR. The 2'-halogen (F or Cl) substituent of the 5-phenylbenzodiazepines increases ligand affinity in vitro because the active conformation of the phenyl N(4)=C(5)-C(1')=C(2') moiety is syn rather than anti. The syn conformation permits the 2'-halogen (F or Cl) atom to interact at the hydrogen bonding site H-2 and form a stable three-centered hydrogen bond in the proposed ligand binding cleft. The 3-thienyl and 2-furyl groups decrease the lipophilicity of the substituent which occupies L(3) but do not form a hydrogen bond at H-2, thus resulting in a diminished affinity at BzR.

  DOI：

  10.1016/0223-5234(96)88259-6

文献信息

• Enantioselective Copper-Catalyzed Borylative Cyclization with Cyclic Imides
  作者：Andrew Whyte、Alexa Torelli、Bijan Mirabi、Mark Lautens

  DOI：10.1021/acs.orglett.9b03144

  日期：2019.10.18

  enantioselective borylative cyclization cascade utilizing cyclic imides has been developed. We employ a highly enantioselective borylcupration process that includes a 1,2-addition to a cyclic imide. The products contain a valuable hemiaminal and boronate handle for further elaborations within a congested framework. This work demonstrates the utility of cyclic imides as simple precursors to unlock access to sought-after

  已经开发了利用环状酰亚胺的对映选择性硼化环化级联反应。我们采用高度对映体选择性的硼基缩合工艺，该工艺包括向环状酰亚胺中添加1,2。该产品包含有价值的Hemiaminal和硼酸盐处理，可在拥挤的框架内进行进一步的处理。这项工作证明了环酰亚胺作为简单的前体的用途，可以用来解锁对广受欢迎的多环二氢吲哚的获取。此外，该报告强调了利用反应性催化中间体开发原本不反应的官能团的能力。
• KOIDZUMI, EHKIO;SIRAKAVA, NORIO;TOMIOKA, XIROMI;TAKEHUTI, MASAKI;OKADA, M+
  作者：KOIDZUMI, EHKIO、SIRAKAVA, NORIO、TOMIOKA, XIROMI、TAKEHUTI, MASAKI、OKADA, M+

  DOI：——

  日期：——
• HUNZIKER, F.;FISCHER, R.;KIPFER, P.;SCHMUTZ, J.;BUERKI, H. R.;FICHENBERGE+, EUR. J. MED. CHEM.-CHIM. THER., 1981, 16, N 5, 391-398
  作者：HUNZIKER, F.、FISCHER, R.、KIPFER, P.、SCHMUTZ, J.、BUERKI, H. R.、FICHENBERGE+

  DOI：——

  日期：——
• Hunziker; Fischer; Kipfer, European Journal of Medicinal Chemistry, 1981, vol. 16, # 5, p. 391 - 398
  作者：Hunziker、Fischer、Kipfer、et al.

  DOI：——

  日期：——
• Syntheses of 5-thienyl and 5-furyl-substituted benzodiazepines: probes of the pharmacophore for benzodiazepine receptor agonists
  作者：W Zhang、R Liu、Q Huang、P Zhang、KF Koehler、B Harris、P Skolnick、JM Cook

  DOI：10.1016/0223-5234(96)88259-6

  日期：1995.1

  The synthesis of 5-thienyl- and 5-furyl-substituted benzodiazepines is described. These compounds were employed to probe the lipophilic pocket (L(3)) of the benzodiazepine receptor (BzR) and to determine the effect of occupation of L(3) on biological activity. Of the new analogs synthesized, the 5-(2-thienyl)-benzodiazepines 6a and 7a displayed high affinity for the BzR (IC50 28 and 18 nM, respectively) and exhibited both anticonvulsant (ED(50) approximate to 9 and 3 mg/kg) and muscle relaxant (ED(50) approximate to 10 and 7 mg/kg) activity. The 5-(3-thienyl)benzodiazepines 6d and 7d displayed only moderate affinity for the BzR (IC50 140 and 110 nM) and exhibited no biological activity (no anticonvulsant or muscle relaxant activity) at doses up to 40 mg/kg. The 5-(2-furyl)benzodiazepines (6b, 7b, 19b and 20b) exhibit low affinities for the BzR. These in vitro and in vivo findings are consistent with our model suggesting that pocket L(3) is very sensitive to lipophilic effects. Thus, decreasing the lipophilicity of functional groups which occupy this region decreases ligand affinity at BzR. The 2'-halogen (F or Cl) substituent of the 5-phenylbenzodiazepines increases ligand affinity in vitro because the active conformation of the phenyl N(4)=C(5)-C(1')=C(2') moiety is syn rather than anti. The syn conformation permits the 2'-halogen (F or Cl) atom to interact at the hydrogen bonding site H-2 and form a stable three-centered hydrogen bond in the proposed ligand binding cleft. The 3-thienyl and 2-furyl groups decrease the lipophilicity of the substituent which occupies L(3) but do not form a hydrogen bond at H-2, thus resulting in a diminished affinity at BzR.