(S)-2-(4-bromophenylsulfonamido)-3-(1H-indol-3-yl)propanoic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (S)-2-(4-bromophenylsulfonamido)-3-(1H-indol-3-yl)propanoic acid
• 英文别名: 2-(4-Bromobenzenesulfonamido)-3-(1H-indol-3-YL)propanoic acid；(2S)-2-[(4-bromophenyl)sulfonylamino]-3-(1H-indol-3-yl)propanoic acid
• 化学式: C₁₇H₁₅BrN₂O₄S
• 分子量: 423.287
• InChiKey: BFYSIYWEMZAFCB-INIZCTEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  108
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-噻吩甲胺 、 (S)-2-(4-bromophenylsulfonamido)-3-(1H-indol-3-yl)propanoic 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 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 以60%的产率得到(S)-2-(4-bromophenylsulfonamido)-3-(1H-indol-3-yl)-N-(thiophen-2-ylmethyl)propanamide
  参考文献：
  名称：

  Synthesis and Structure–Activity Relationships of Arylsulfonamides as AIMP2-DX2 Inhibitors for the Development of a Novel Anticancer Therapy

  摘要：

  AIMP2-DX2, a splicing variant of AIMP2, is up-regulated in lung cancer, possesses oncogenic activity, and results in tumorigenesis. Specifically inhibiting the interaction between AIMP2-DX2 and HSP70 to suppress AIMP2-DX2-dependent cancers with small molecules is considered a promising avenue for cancer therapeutics. Optimization of hit BC-DXI-04 (IC50 = 40.1 mu M) provided new potent sulfonamide based AIMP2-DX2 inhibitors. Among these, BC-DXI-843 showed improved inhibition against AIMP2-DX2 (IC50 = 0.92 mu M) with more than 100-fold selectivity over AIMP2 in a luciferase assay. Several binding assays indicated that this compound effectively induces cancer cell apoptosis by specifically interrupting the interaction between DX2 and HSP70, which leads to the degradation of DX2 via Siah1-mediated ubiquitination. More importantly, BC-DXI-843 demonstrated in vivo efficacy in a tumor xenograft mouse model (H460 cells) at a dosage of 50 mg/kg, suggesting it as a promising lead for development of novel therapeutics targeting AIMP2-DX2 in lung cancer.

  DOI：

  10.1021/acs.jmedchem.9b01961
• 作为产物：
  描述：

  4-溴苯磺酰氯 、 L-色氨酸 在 sodium hydroxide 作用下， 以 水 为溶剂， 以54%的产率得到(S)-2-(4-bromophenylsulfonamido)-3-(1H-indol-3-yl)propanoic acid
  参考文献：
  名称：

  Synthesis and Structure–Activity Relationships of Arylsulfonamides as AIMP2-DX2 Inhibitors for the Development of a Novel Anticancer Therapy

  摘要：

  AIMP2-DX2, a splicing variant of AIMP2, is up-regulated in lung cancer, possesses oncogenic activity, and results in tumorigenesis. Specifically inhibiting the interaction between AIMP2-DX2 and HSP70 to suppress AIMP2-DX2-dependent cancers with small molecules is considered a promising avenue for cancer therapeutics. Optimization of hit BC-DXI-04 (IC50 = 40.1 mu M) provided new potent sulfonamide based AIMP2-DX2 inhibitors. Among these, BC-DXI-843 showed improved inhibition against AIMP2-DX2 (IC50 = 0.92 mu M) with more than 100-fold selectivity over AIMP2 in a luciferase assay. Several binding assays indicated that this compound effectively induces cancer cell apoptosis by specifically interrupting the interaction between DX2 and HSP70, which leads to the degradation of DX2 via Siah1-mediated ubiquitination. More importantly, BC-DXI-843 demonstrated in vivo efficacy in a tumor xenograft mouse model (H460 cells) at a dosage of 50 mg/kg, suggesting it as a promising lead for development of novel therapeutics targeting AIMP2-DX2 in lung cancer.

  DOI：

  10.1021/acs.jmedchem.9b01961

文献信息

• NOVEL COMPOUND HAVING ANTICANCER ACTIVITY, AND METHOD FOR PRODUCING SAME
  申请人：Medicinal Bioconvergence Research Center

  公开号：EP3939968A1

  公开（公告）日：2022-01-19

  The present invention pertains to a novel compound having anticancer activity, and a method for producing same, and more specifically, to a novel compound that exhibits excellent anticancer activity by inhibiting the expression of AIMP2-DX2, and a method for producing same. The compound represented by chemical formula 1 according to the present invention is highly effective in inhibiting the expression of AIMP2-DX2, and thus can be very advantageously used for the development of agents for treating various diseases, in particular cancer, caused by AIMP2-DX2.

  本发明涉及一种具有抗癌活性的新型化合物及其生产方法，更具体地说，涉及一种通过抑制 AIMP2-DX2 的表达而表现出优异抗癌活性的新型化合物及其生产方法。根据本发明的化学式 1 所代表的化合物在抑制 AIMP2-DX2 的表达方面非常有效，因此可以非常有利地用于开发治疗由 AIMP2-DX2 引起的各种疾病，特别是癌症的药物。
• [EN] NOVEL COMPOUND HAVING ANTICANCER ACTIVITY, AND METHOD FOR PRODUCING SAME<br/>[FR] NOUVEAU COMPOSÉ AYANT UNE ACTIVITÉ ANTICANCÉREUSE, ET PROCÉDÉ DE PRODUCTION ASSOCIÉ<br/>[KO] 항암활성을 갖는 신규한 화합물 및 이의 제조방법
  申请人：MEDICINAL BIOCONVERGENCE RES CT

  公开号：WO2020204548A1

  公开（公告）日：2020-10-08

  본 발명은 항암활성을 갖는 신규한 화합물 및 이의 제조방법에 관한 것으로, 보다 상세하게는 AIMP2-DX2의 발현을 억제하여 우수한 항암활성을 나타내는 신규한 화합물 및 이의 제조방법에 관한 것이다. 본 발명에 따른 상기 화학식 1로 표시되는 화합물은 AIMP2-DX2의 발현을 저해하는 효과가 매우 우수하여, AIMP2-DX2에 의해 유발되는 다양한 질환들, 특히 암 치료제 개발에 매우 유용하게 활용될 수 있다.