N-(4-methylbenzoyl)-L-leucine | 166597-76-8

• 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: N-(4-methylbenzoyl)-L-leucine
• 英文别名: N-(p-methylbenzoyl)-L-leucine；(2S)-4-methyl-2-[(4-methylbenzoyl)amino]pentanoic acid
• CAS: 166597-76-8
• 化学式: C₁₄H₁₉NO₃
• mdl: MFCD16377986
• 分子量: 249.31
• InChiKey: MUPAOMLUTMORSO-LBPRGKRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.428
• 拓扑面积：
  66.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(4-methylbenzoyl)-L-leucine 在 lithium hydroxide 、 N,N'-二异丙基碳二亚胺 作用下， 以 乙二醇二甲醚 、 二氯甲烷 为溶剂， 反应 35.5h， 生成 1-(tert-butyloxycarbonylamino)-3-[N-(4-methylbenzoyl)-L-leucyl-L-prolyl-amino]propane
  参考文献：
  名称：

  新型蓝肽衍生的胰蛋白酶样丝氨酸蛋白酶低分子量抑制剂

  摘要：

  本文涉及利用具有有趣生物活性的蓝细菌的次级代谢产物氰肽作为新的先导结构的新型低分子量凝血酶抑制剂的设计、合成和抑制试验。从铜绿素 98-B (1) 作为先导结构开始，我们开发并合成了新的、选择性作用的丝氨酸蛋白酶抑制剂（RA-1005 和 RA-1009，它们是进一步结构-活性研究的合适靶点。

  DOI：

  10.1002/ardp.200300765
• 作为产物：
  描述：

  L-亮氨酸苄基酯 在 palladium on activated charcoal 、 氢气 、 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 甲醇 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 N-(4-methylbenzoyl)-L-leucine
  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

• Dual space divergence in small molecule quasiracemates: benzoyl leucine and phenylalanine assemblies
  作者：Katelyn N. Koch、Aaron J. Teo、Kraig A. Wheeler

  DOI：10.1039/d3cc06212k

  日期：——

  Small molecule quasiracemates developed with two points of structural difference were prepared using benzoyl leucine and phenylalanine molecular frameworks and CH₃/Cl or H/CF₃ pendant groups.

  利用苯甲酰基亮氨酸和苯丙氨酸分子框架以及 CH3/Cl 或 H/CF3 下垂基团，制备出了具有两点结构差异的小分子类冰酸盐。
• Synthesis and Structure–Activity Relationships of Arylsulfonamides as AIMP2-DX2 Inhibitors for the Development of a Novel Anticancer Therapy
  作者：Aneesh Sivaraman、Dae Gyu Kim、Deepak Bhattarai、Minkyoung Kim、Hwa Young Lee、Semi Lim、Jiwon Kong、Ja-il Goo、Seunghwan Shim、Seungbeom Lee、Young-Ger Suh、Yongseok Choi、Sunghoon Kim、Kyeong Lee

  DOI：10.1021/acs.jmedchem.9b01961

  日期：2020.5.28

  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.
• New Cyanopeptide-Derived Low Molecular Weight Inhibitors of trypsin-like Serine Proteases
  作者：Gregor Radau、Sonja Schermuly、Alexandra Fritsche

  DOI：10.1002/ardp.200300765

  日期：2003.8

  and inhibition tests of new low molecular weight thrombin inhibitors utilizing cyanopeptides, the secondary metabolites of cyanobacteria with interesting biological activities, as new lead structures. Starting with aeruginosin 98‐B (1) as a lead structure, we have developed and synthesised new, selective acting inhibitors of serine proteases (RA‐1005 and RA‐1009, which are suitable targets for further

  本文涉及利用具有有趣生物活性的蓝细菌的次级代谢产物氰肽作为新的先导结构的新型低分子量凝血酶抑制剂的设计、合成和抑制试验。从铜绿素 98-B (1) 作为先导结构开始，我们开发并合成了新的、选择性作用的丝氨酸蛋白酶抑制剂（RA-1005 和 RA-1009，它们是进一步结构-活性研究的合适靶点。