5-(2-cyanophenylamino)-3-methyl-5-oxopentanoic acid | 1273782-76-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-(2-cyanophenylamino)-3-methyl-5-oxopentanoic acid
• 英文别名: 5-(2-cyanoanilino)-3-methyl-5-oxopentanoic acid
• CAS: 1273782-76-5
• 化学式: C₁₃H₁₄N₂O₃
• 分子量: 246.266
• InChiKey: DIMISFDDUBMGRR-UHFFFAOYSA-N

物化性质

• 沸点：
  541.1±35.0 °C(Predicted)
• 密度：
  1.24±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  90.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-氨基-9-乙基咔唑 、 5-(2-cyanophenylamino)-3-methyl-5-oxopentanoic acid 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 20.0h， 以40%的产率得到N-(2-cyanophenyl)-N'-(9-ethyl-9H-carbazol-3-yl)-3-methylpentanediamide
  参考文献：
  名称：

  Identification of novel quinazolinedione derivatives as RORγt inverse agonist

  摘要：

  Novel small molecules were synthesized and evaluated as retinoic acid receptor-related orphan receptor-gamma t (ROR gamma t) inverse agonists for the treatment of inflammatory and autoimmune diseases. A hit compound, 1, was discovered by high-throughput screening of our compound library. The structure-activity relationship (SAR) study of compound 1 showed that the introduction of a chlorine group at the 3-position of 4-cyanophenyl moiety increased the potency and a 3-methylpentane-1,5-diamide linker is favorable for the activity. The carbazole moiety of 1 was also optimized; a quinazolinedione derivative 18i suppressed the increase of IL-17A mRNA level in the lymph node of a rat model of experimental autoimmune encephalomyelitis (EAE) upon oral administration. These results indicate that the novel quinazolinedione derivatives have great potential as orally available small-molecule ROR gamma t inverse agonists for the treatment of Th17-driven autoimmune diseases. A U-shaped bioactive conformation of this chemotype with ROR gamma t protein was also observed. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2017.12.039
• 作为产物：
  描述：

  3-甲基戊二酸酐 、 2-氨基苯甲腈 以 四氢呋喃 为溶剂， 反应 46.0h， 以to give 5-(2-cyanophenylamino)-3-methyl-5-oxopentanoic acid (2.230 g, 9.06 mmol, 91%) as a white powder的产率得到5-(2-cyanophenylamino)-3-methyl-5-oxopentanoic acid
  参考文献：
  名称：

  CONDENSED HETEROCYCLIC COMPOUND

  摘要：

  本发明提供了一种具有RORγt抑制作用的融合杂环化合物。本发明涉及一种由式(I')表示的化合物：其中每个符号如规范中所定义，前提是2-（2-（（4-氰基苯基）氨基）-2-氧代乙氧基）-N-（9-乙基-9H-咔唑-3-基）乙酰胺和N-（4-氰基苯基）-N'-(9-乙基-9H-咔唑-3-基)-3-甲基戊二酰胺被排除，或其盐。

  公开号：

  US20140228409A1

文献信息

• Condensed heterocyclic compound
  申请人：Takeda Pharmaceutical Company Limited

  公开号：US09120776B2

  公开（公告）日：2015-09-01

  The present invention provides a fused heterocyclic compound having an RORγt inhibitory action. The present invention relates to a compound represented by the formula (I′): wherein each symbol is as defined in the specification, provided that 2-(2-((4-cyanophenyl)amino)-2-oxoethoxy)-N-(9-ethyl-9H-carbazol-3-yl)acetamide and N-(4-cyanophenyl)-N′-(9-ethyl-9H-carbazol-3-yl)-3-methylpentanediamide are excluded, or a thereof.

  本发明提供了一种具有RORγt抑制作用的融合杂环化合物。本发明涉及一种由式(I')表示的化合物：其中每个符号如规范中所定义，前提是2-(2-((4-氰基苯基)氨基)-2-氧代乙氧基)-N-(9-乙基-9H-咔唑-3-基)乙酰胺和N-(4-氰基苯基)-N'-(9-乙基-9H-咔唑-3-基)-3-甲基戊二酰胺被排除，或者其衍生物。
• CONDENSED HETEROCYCLIC COMPOUND
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP2759533B1

  公开（公告）日：2017-08-02
• US9120776B2
  申请人：——

  公开号：US9120776B2

  公开（公告）日：2015-09-01
• Identification of novel quinazolinedione derivatives as RORγt inverse agonist
  作者：Yoshiyuki Fukase、Ayumu Sato、Yoshihide Tomata、Atsuko Ochida、Mitsunori Kono、Kazuko Yonemori、Keiko Koga、Toshitake Okui、Masashi Yamasaki、Yasushi Fujitani、Hideyuki Nakagawa、Ryoukichi Koyama、Masaharu Nakayama、Robert Skene、Bi-Ching Sang、Isaac Hoffman、Junya Shirai、Satoshi Yamamoto

  DOI：10.1016/j.bmc.2017.12.039

  日期：2018.2

  Novel small molecules were synthesized and evaluated as retinoic acid receptor-related orphan receptor-gamma t (ROR gamma t) inverse agonists for the treatment of inflammatory and autoimmune diseases. A hit compound, 1, was discovered by high-throughput screening of our compound library. The structure-activity relationship (SAR) study of compound 1 showed that the introduction of a chlorine group at the 3-position of 4-cyanophenyl moiety increased the potency and a 3-methylpentane-1,5-diamide linker is favorable for the activity. The carbazole moiety of 1 was also optimized; a quinazolinedione derivative 18i suppressed the increase of IL-17A mRNA level in the lymph node of a rat model of experimental autoimmune encephalomyelitis (EAE) upon oral administration. These results indicate that the novel quinazolinedione derivatives have great potential as orally available small-molecule ROR gamma t inverse agonists for the treatment of Th17-driven autoimmune diseases. A U-shaped bioactive conformation of this chemotype with ROR gamma t protein was also observed. (C) 2017 Elsevier Ltd. All rights reserved.