(2-amino-5-chlorophenyl)(2-furyl)methanone | 60514-58-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (2-amino-5-chlorophenyl)(2-furyl)methanone
• 英文别名: 2-amino-5-chlorophenyl 2-furyl ketone；4-chloro-2-(2'-furoyl)aniline；(2-Amino-5-chlorophenyl)-(furan-2-yl)methanone
• CAS: 60514-58-1
• 化学式: C₁₁H₈ClNO₂
• 分子量: 221.643
• InChiKey: OXZKFTFVOCOOMQ-UHFFFAOYSA-N

物化性质

• 熔点：
  113-114 °C
• 沸点：
  408.4±40.0 °C(Predicted)
• 密度：
  1.346±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 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：
  56.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (2-amino-5-chlorophenyl)(2-furyl)methanone 在 氨 、 sodium hydride 、 碳酸氢钠 作用下， 以 甲醇 、 氯仿 为溶剂， 反应 6.91h， 生成 WZ-148
  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
• 作为产物：
  描述：

  2-氨基-5-氯苯甲酸 在 sodium hydroxide 、 正丁基锂 作用下， 以 乙醇 为溶剂， 反应 8.5h， 生成 (2-amino-5-chlorophenyl)(2-furyl)methanone
  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

• A novel class of sodium/calcium exchanger inhibitor: design, synthesis, and structure–activity relationships of 3,4-dihydro-2(1H)-quinazolinone derivatives
  作者：Hirohiko Hasegawa、Masami Muraoka、Mikiko Ohmori、Kazuki Matsui、Atsuyuki Kojima

  DOI：10.1016/j.bmc.2005.03.019

  日期：2005.6

  Design, synthesis, and structure-activity relationships of 3,4-dihydro-2(1H)-quinazolinone derivatives as inhibitors of the sodium/calcium (Na(+)/Ca(2+)) exchanger are discussed. These studies, based on a lead compound 9a, which was identified in our library, involved systematic modification of three regions and revealed that (1) the 3,4-dihydro-2(1H)-quinazolinone having a tertiary amino alkyl side

  设计，合成，和构效关系的3,4-dihydro-2（1H）-quinazolinone衍生物作为钠/钙（Na（+）/ Ca（2+））交换剂的抑制剂进行了讨论。这些研究基于在我们的图书馆中鉴定出的先导化合物9a，涉及三个区域的系统修饰，并揭示了（1）3,4-二氢-2（1H）-喹唑啉酮在3位对活性至关重要，（2）非取代的苯环最适合高活性，并且（3）引入4-取代的哌啶部分增强了活性，特别是4-苄基哌啶-1-基显示出很强的活性。抑制活性。基于这些SAR研究，发现了一种结构新颖且高效的Na（+）/ Ca（2+）交换剂12g（SM-15811）抑制剂。特别是，SM-15811直接抑制Na（+）依赖的Ca（2+）流入，通过具有高效力的心肌细胞中的Na（+）/ Ca（2+）交换剂。该活性比先导化合物9a和SM-15811对心肌缺血再灌注损伤具有保护作用的效力强了将近两个数量级。这些Na（+）/ Ca（2+
• Discovery of a novel potent Na + /Ca 2+ exchanger inhibitor: design, synthesis and structure–activity relationships of 3,4-dihydro-2(1 H )-quinazolinone derivatives
  作者：Hirohiko Hasegawa、Masami Muraoka、Kazuki Matsui、Atsuyuki Kojima

  DOI：10.1016/s0960-894x(03)00744-3

  日期：2003.10

  Design, synthesis and structure-activity relationships for 3,4-dihydro-2(1H)-quinazolinone derivatives with the inhibitory activities of the Na(+)/Ca(2+) exchanger are discussed. These studies based on lead compound 1a lead to the discovery of a structurally novel and highly potent inhibitor against the Na(+)/Ca(2+) exchanger 4f (SM-15811), which directly inhibited the Na(+)-dependent Ca(2+) influx

  设计，合成和构效关系的3,4-dihydro-2（1H）-喹唑啉酮衍生物具有Na（+）/ Ca（2+）交换器的抑制活性。这些基于铅化合物1a的研究导致发现了一种结构新颖且高效的Na（+）/ Ca（2+）交换子4f（SM-15811）抑制剂，该抑制剂直接抑制Na（+）依赖性Ca （2+）通过Na（+）/ Ca（2+）交换剂流入具有高效力的心肌细胞。
• The Synthesis of Substituted 2-Aminophenyl Heterocyclic Ketones
  作者：R. I. Fryer、P. Zhang、R. Rios

  DOI：10.1080/00397919308013295

  日期：1993.4

  Abstract The synthesis of substituted 2-aminophenyl heterocyclic ketones, key intermediates to the preparation of 1,4-benzodiazepines has been achieved in one step and in good, yield from the corresponding anthranilic acid, by treatment with heterocyclic lithium reagents and chlorotrimethylsilane.

  摘要 取代的2-氨基苯基杂环酮是制备1,4-苯二氮卓类的关键中间体，通过杂环锂试剂和氯三甲基硅烷处理，一步合成，相应的邻氨基苯甲酸收率良好。
• US3950526A
  申请人：——

  公开号：US3950526A

  公开（公告）日：1976-04-13
• US4647560A
  申请人：——

  公开号：US4647560A

  公开（公告）日：1987-03-03