1H-indole-2,3-dione-3-(1,3-benzoxazol-2-ylhydrazone) | 91837-56-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 1H-indole-2,3-dione-3-(1,3-benzoxazol-2-ylhydrazone)
• 英文别名: 3-[2-(1,3-benzoxazol-2-yl)hydrazinyl]indol-2-one
• CAS: 91837-56-8
• 化学式: C₁₅H₁₀N₄O₂
• 分子量: 278.27
• InChiKey: NWUCBUGDPJNKAC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  21.0
• 可旋转键数：
  2.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  79.52
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  1H-indole-2,3-dione-3-(1,3-benzoxazol-2-ylhydrazone) 、 zinc(II) chloride 以 乙醇 为溶剂， 生成 {Zn(N-(2-benzoxazolyl)-N'-(2oxo-3-indolinylidene)hydrazine)Cl2(H2O)}
  参考文献：
  名称：

  Atre, Vasudha; Raju, V. Jaya Tyaga; Ratnam, K. Jeeva, Indian Journal of Chemistry, Section A: Inorganic, Physical, Theoretical and Analytical, 1984, vol. 23, # 8, p. 691 - 693

  摘要：

  DOI：
• 作为产物：
  描述：

  2-吲哚酮 、 2-肼基-1,3-苯并噁唑 在 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 3.0h， 以36%的产率得到1H-indole-2,3-dione-3-(1,3-benzoxazol-2-ylhydrazone)
  参考文献：
  名称：

  PO‐322 exerts potent immunosuppressive effects in vitro and in vivo by selectively inhibiting SGK1 activity

  摘要：

  Background and PurposeImmunosuppressive drugs have shown great promise in treating autoimmune diseases in recent years. A series of novel oxazole derivatives were screened for their immunosuppressive activity. PO‐322 [1H‐indole‐2,3‐dione 3‐(1,3‐benzoxazol‐2‐ylhydrazone)] was identified as the most effective of these compounds. Here, we have investigated the mechanism(s) underlying the inhibition of T‐cell proliferation in vitro by PO‐322, as well as its effects on the delayed‐type hypersensitivity (DTH) response and imiquimod‐induced dermatitis in vivo.Experimental ApproachT‐cell proliferation and apoptosis were analysed with flow cytometry. Cell viability was assessed with a CCK‐8 assay. Protein kinase activity was assessed by SelectScreen Kinase Profiling Services. The phosphorylation of signal‐regulated molecules was measured by Western blot. Cytokine levels were determined by elisa. The effect of PO‐322 on DTH and imiquimod‐induced dermatitis was evaluated in BALB/c mice.Key ResultsPO‐322 inhibited human T‐cell proliferation with anti‐CD3/anti‐CD28 mAbs or alloantigen without significant cytotoxicity. Importantly, PO‐322 was a selective inhibitor of the serum‐ and glucocorticoid‐regulated kinase 1 (SGK1) and decreased NDRG1 phosphorylation but not p70S6K, STAT5, Akt, or ERK1/2 phosphorylation. Furthermore, PO‐322 inhibited IFN‐γ, IL‐6, and IL‐17 expression but not IL‐10 expression. Finally, treatment with PO‐322 was safe and effective for ameliorating the DTH response and imiquimod‐induced dermatitis in mice.Conclusions and ImplicationsPO‐322 exerted immunosuppressive activity in vitro and in vivo by selectively inhibiting SGK1 activity. PO‐322 represents a potential lead compound for the design and development of new drugs for the treatment of autoimmune diseases.

  DOI：

  10.1111/bph.14926

文献信息

• Atre, Vasudha; Raju, V. Jaya Tyaga; Ratnam, K. Jeeva, Indian Journal of Chemistry, Section A: Inorganic, Physical, Theoretical and Analytical, 1984, vol. 23, # 8, p. 691 - 693
  作者：Atre, Vasudha、Raju, V. Jaya Tyaga、Ratnam, K. Jeeva、Ganorkar, M. C.

  DOI：——

  日期：——
• PO‐322 exerts potent immunosuppressive effects in vitro and in vivo by selectively inhibiting SGK1 activity
  作者：Yi Lai、Xing‐Yan Luo、Hui‐Jie Guo、Si‐Yu Wang、Jing Xiong、Shu‐Xia Yang、Li‐Mei Li、Qiang Zou、Chun‐Fen Mo、Yan‐Tang Wang、Yang Liu

  DOI：10.1111/bph.14926

  日期：2020.4

  Background and PurposeImmunosuppressive drugs have shown great promise in treating autoimmune diseases in recent years. A series of novel oxazole derivatives were screened for their immunosuppressive activity. PO‐322 [1H‐indole‐2,3‐dione 3‐(1,3‐benzoxazol‐2‐ylhydrazone)] was identified as the most effective of these compounds. Here, we have investigated the mechanism(s) underlying the inhibition of T‐cell proliferation in vitro by PO‐322, as well as its effects on the delayed‐type hypersensitivity (DTH) response and imiquimod‐induced dermatitis in vivo.Experimental ApproachT‐cell proliferation and apoptosis were analysed with flow cytometry. Cell viability was assessed with a CCK‐8 assay. Protein kinase activity was assessed by SelectScreen Kinase Profiling Services. The phosphorylation of signal‐regulated molecules was measured by Western blot. Cytokine levels were determined by elisa. The effect of PO‐322 on DTH and imiquimod‐induced dermatitis was evaluated in BALB/c mice.Key ResultsPO‐322 inhibited human T‐cell proliferation with anti‐CD3/anti‐CD28 mAbs or alloantigen without significant cytotoxicity. Importantly, PO‐322 was a selective inhibitor of the serum‐ and glucocorticoid‐regulated kinase 1 (SGK1) and decreased NDRG1 phosphorylation but not p70S6K, STAT5, Akt, or ERK1/2 phosphorylation. Furthermore, PO‐322 inhibited IFN‐γ, IL‐6, and IL‐17 expression but not IL‐10 expression. Finally, treatment with PO‐322 was safe and effective for ameliorating the DTH response and imiquimod‐induced dermatitis in mice.Conclusions and ImplicationsPO‐322 exerted immunosuppressive activity in vitro and in vivo by selectively inhibiting SGK1 activity. PO‐322 represents a potential lead compound for the design and development of new drugs for the treatment of autoimmune diseases.