tert-butyl 4-(4-(ethoxycarbonyl)-1-(4-isopropylphenyl)-1H-pyrazol-5-yl)piperidine-1-carboxylate | 957247-54-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: tert-butyl 4-(4-(ethoxycarbonyl)-1-(4-isopropylphenyl)-1H-pyrazol-5-yl)piperidine-1-carboxylate
• 英文别名: tert-butyl-4-(4-(ethoxycarbonyl)-1-(4-isopropylphenyl)-1H-pyrazol-5-yl)piperidine-1-carboxylate；Tert-butyl 4-[4-(ethoxycarbonyl)-1-[4-(propan-2-YL)phenyl]-1H-pyrazol-5-YL]piperidine-1-carboxylate；tert-butyl 4-[4-ethoxycarbonyl-2-(4-propan-2-ylphenyl)pyrazol-3-yl]piperidine-1-carboxylate
• CAS: 957247-54-0
• 化学式: C₂₅H₃₅N₃O₄
• mdl: MFCD14776524
• 分子量: 441.571
• InChiKey: JFVGXLBARVKIOE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  32
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  73.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(4-(ethoxycarbonyl)-1-(4-isopropylphenyl)-1H-pyrazol-5-yl)piperidine-1-carboxylate 在 4-二甲氨基吡啶 、 乙醇 、 N,N'-二环己基碳二亚胺 、 sodium hydroxide 作用下， 以 二氯甲烷 为溶剂， 反应 68.0h， 生成 tert-butyl-4-(4-((3,5-dimethylphenyl)carbamoyl)-1-(4-isopropylphenyl)-1H-pyrazol-5-yl)piperidine-1-carboxylate
  参考文献：
  名称：

  Compounds and methods for treating cancer by inhibiting the urokinase receptor

  摘要：

  提供了用于治疗或预防与结合尿激酶受体相关的癌症的化合物和方法。这些化合物影响的生物过程包括细胞迁移、细胞生长、细胞粘附、血管生成、癌细胞入侵、细胞凋亡、肿瘤形成、肿瘤进展、转移、细胞外基质降解、周细胞蛋白水解、纤溶酶原激活、细胞外蛋白酶水平变化以及VEGF受体水平变化。

  公开号：

  US09745288B2
• 作为产物：
  描述：

  tert-butyl 4-(2,2-dimethyl-4,6-dioxo-1,3-dioxane-5-carbonyl)piperidine-1-carboxylate 在 乙酸酐 、 碳酸氢钠 作用下， 以 二氯甲烷 为溶剂， 反应 144.0h， 生成 tert-butyl 4-(4-(ethoxycarbonyl)-1-(4-isopropylphenyl)-1H-pyrazol-5-yl)piperidine-1-carboxylate
  参考文献：
  名称：

  Virtual Screening Targeting the Urokinase Receptor, Biochemical and Cell-Based Studies, Synthesis, Pharmacokinetic Characterization, and Effect on Breast Tumor Metastasis

  摘要：

  Virtual screening targeting the urokinase receptor (uPAR) led to (+/-)-3-(benzo[d][1,3]dioxol-5-yl)-N-(benzo[d][1,3]dioxol-5-ylmethyl)-4-phenylbutan-1-amine 1 (IPR-1) and N-(3,5-dimethylphenyl)-1-(4-isopropylphenyl)-5-(piperidin-4-yl)-1H-pyrazole-4-carboxamide 3 (IPR-69). Synthesis of an analogue of!, namely, 2 (IPR-9), and 3 led to breast MDA-MB-231 invasion, migration and adhesion assays with IC50 near 30 mu M. Both compounds blocked angiogenesis with IC50 of 3 mu M. Compounds 2 and 3 inhibited cell growth with IC50 of 6 and 18 mu M and induced apoptosis. Biochemical assays revealed leadlike properties for 3, but not 2. Compound 3 administered orally reached peak concentration of nearly 40 mu M with a half-life of about 2 h. In NOD-S CID mice inoculated with breast TMD-231 cells in their mammary fat pads, compound 3 showed a 20% reduction in tumor volumes and less extensive metastasis was observed for the treated mice. The suitable pharmacokinetic properties of 3 and the encouraging preliminary results in metastasis make it an ideal starting point for next generation compounds.

  DOI：

  10.1021/jm200782y

文献信息

• Compounds and methods for treating cancer by inhibiting the urokinase receptor
  申请人：Meroueh Samy O.

  公开号：US09745288B2

  公开（公告）日：2017-08-29

  Compounds and methods for treating or preventing cancer associated with binding to the urokinase receptor are provided. Biological processes affected by the compounds include cell migration, cell growth, cell adhesion, angiogenesis, cancer cell invasion, apoptosis, tumor formation, tumor progression, metastasis, degradation of the extracellular matrix, pericellular proteolysis, activation of plasminogen, changes in the levels of an extracellular protease, and changes in the levels of a VEGF receptor.

  提供了用于治疗或预防与结合尿激酶受体相关的癌症的化合物和方法。这些化合物影响的生物过程包括细胞迁移、细胞生长、细胞粘附、血管生成、癌细胞入侵、细胞凋亡、肿瘤形成、肿瘤进展、转移、细胞外基质降解、周细胞蛋白水解、纤溶酶原激活、细胞外蛋白酶水平变化以及VEGF受体水平变化。
• COMPOUNDS AND METHODS FOR TREATING CANCER BY INHIBITING THE UROKINASE RECEPTOR
  申请人：Meroueh Samy O.

  公开号：US20150051247A1

  公开（公告）日：2015-02-19

  Compounds and methods for treating or preventing cancer associated with binding to the urokinase receptor are provided. Biological processes affected by the compounds include cell migration, cell growth, cell adhesion, angiogenesis, cancer cell invasion, apoptosis, tumor formation, tumor progression, metastasis, degradation of the extracellular matrix, pericellular proteolysis, activation of plasminogen, changes in the levels of an extracellular protease, and changes in the levels of a VEGF receptor.

  本发明提供了用于治疗或预防与结合尿激酶受体相关的癌症的化合物和方法。这些化合物影响的生物过程包括细胞迁移、细胞生长、细胞黏附、血管生成、癌细胞侵袭、细胞凋亡、肿瘤形成、肿瘤进展、转移、细胞外基质降解、周细胞蛋白酶解、纤溶酶原激活、细胞外蛋白酶水平变化以及VEGF受体水平变化。
• [EN] COMPOUNDS AND METHODS FOR TREATING CANCER BY INHIBITING THE UROKINASE RECEPTOR<br/>[FR] COMPOSÉS ET MÉTHODES DE TRAITEMENT DU CANCER PAR L'INHIBITION DU RÉCEPTEUR DE L'UROKINASE
  申请人：UNIV INDIANA RES & TECH CORP

  公开号：WO2013025939A9

  公开（公告）日：2013-04-11
• US9745288B2
  申请人：——

  公开号：US9745288B2

  公开（公告）日：2017-08-29
• Virtual Screening Targeting the Urokinase Receptor, Biochemical and Cell-Based Studies, Synthesis, Pharmacokinetic Characterization, and Effect on Breast Tumor Metastasis
  作者：Fang Wang、Jing Li、Anthony L. Sinn、W. Eric Knabe、May Khanna、Inha Jo、Jayne M. Silver、Kyungsoo Oh、Liwei Li、George E. Sandusky、George W. Sledge、Harikrishna Nakshatri、David R. Jones、Karen E. Pollok、Samy O. Meroueh

  DOI：10.1021/jm200782y

  日期：2011.10.27

  Virtual screening targeting the urokinase receptor (uPAR) led to (+/-)-3-(benzo[d][1,3]dioxol-5-yl)-N-(benzo[d][1,3]dioxol-5-ylmethyl)-4-phenylbutan-1-amine 1 (IPR-1) and N-(3,5-dimethylphenyl)-1-(4-isopropylphenyl)-5-(piperidin-4-yl)-1H-pyrazole-4-carboxamide 3 (IPR-69). Synthesis of an analogue of!, namely, 2 (IPR-9), and 3 led to breast MDA-MB-231 invasion, migration and adhesion assays with IC50 near 30 mu M. Both compounds blocked angiogenesis with IC50 of 3 mu M. Compounds 2 and 3 inhibited cell growth with IC50 of 6 and 18 mu M and induced apoptosis. Biochemical assays revealed leadlike properties for 3, but not 2. Compound 3 administered orally reached peak concentration of nearly 40 mu M with a half-life of about 2 h. In NOD-S CID mice inoculated with breast TMD-231 cells in their mammary fat pads, compound 3 showed a 20% reduction in tumor volumes and less extensive metastasis was observed for the treated mice. The suitable pharmacokinetic properties of 3 and the encouraging preliminary results in metastasis make it an ideal starting point for next generation compounds.