tert-butyl 2-amino-4-methyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 英文名称: tert-butyl 2-amino-4-methyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate
• 英文别名: Tert-butyl 2-amino-4-methyl-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxylate；tert-butyl 2-amino-4-methyl-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxylate
• 化学式: C₁₄H₂₁NO₂S
• mdl: MFCD25731495
• 分子量: 267.392
• InChiKey: STIFDTOMLBKKNS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.642
• 拓扑面积：
  80.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl 2-amino-4-methyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate 在 calcium carbonate 作用下， 以 吡啶 、 二氯甲烷 、 水 为溶剂， 反应 3.0h， 生成 tert-butyl 2-(3-(3-methoxyphenyl)thioureido)-4-methyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate
  参考文献：
  名称：

  Discovery, structure-activity relationship study and biological evaluation of 2-thioureidothiophene-3-carboxylates as a novel class of C-X-C chemokine receptor 2 (CXCR2) antagonists

  摘要：

  The C-X-C motif ligand 8 and C-X-C chemokine receptor 2 (CXCL8-CXCR2) axis is involved in pathogenesis of various diseases including inflammation and cancers. Various CXCR2 antagonists are under development for several diseases. Our previous high-throughput cell-based assay specific for CXCR2 has identified a pyrimidine-based compound CX797 acting on CXCR2 down-stream signaling. A lead optimization campaign through scaffold-hopping strategy led to a series of 2-thioureidothiophene-3-carboxylates (TUTP) as novel CXCR2 antagonists. Structure-activity relationship study of TUTPs led to the identification of compound 52 that significantly inhibited CXCR2-mediated beta-arrestin recruitment signaling (IC50 = 1.1 +/- 0.01 mu M) with negligible effect on CXCL8-mediated cAMP signaling and calcium flux. Similar to the known CXCR2 antagonist SB265610, compound 52 inhibited CXCL8-CXCR2 induced phosphorylation of ERK1/2. TUTP compounds also inhibited CXCL8-mediated cell migration and showed synergy with doxorubicin in ovarian cancer cells, thereby supporting TUTPs as promising compounds for cancer treatment. (C) 2020 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2020.112387
• 作为产物：
  描述：

  氰乙酸叔丁酯 、 2-甲基环己酮 在 吗啉 、 sulfur 作用下， 反应 48.0h， 以73%的产率得到tert-butyl 2-amino-4-methyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate
  参考文献：
  名称：

  Discovery, structure-activity relationship study and biological evaluation of 2-thioureidothiophene-3-carboxylates as a novel class of C-X-C chemokine receptor 2 (CXCR2) antagonists

  摘要：

  The C-X-C motif ligand 8 and C-X-C chemokine receptor 2 (CXCL8-CXCR2) axis is involved in pathogenesis of various diseases including inflammation and cancers. Various CXCR2 antagonists are under development for several diseases. Our previous high-throughput cell-based assay specific for CXCR2 has identified a pyrimidine-based compound CX797 acting on CXCR2 down-stream signaling. A lead optimization campaign through scaffold-hopping strategy led to a series of 2-thioureidothiophene-3-carboxylates (TUTP) as novel CXCR2 antagonists. Structure-activity relationship study of TUTPs led to the identification of compound 52 that significantly inhibited CXCR2-mediated beta-arrestin recruitment signaling (IC50 = 1.1 +/- 0.01 mu M) with negligible effect on CXCL8-mediated cAMP signaling and calcium flux. Similar to the known CXCR2 antagonist SB265610, compound 52 inhibited CXCL8-CXCR2 induced phosphorylation of ERK1/2. TUTP compounds also inhibited CXCL8-mediated cell migration and showed synergy with doxorubicin in ovarian cancer cells, thereby supporting TUTPs as promising compounds for cancer treatment. (C) 2020 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2020.112387

文献信息

• Discovery, structure-activity relationship study and biological evaluation of 2-thioureidothiophene-3-carboxylates as a novel class of C-X-C chemokine receptor 2 (CXCR2) antagonists
  作者：Ding Xue、Wenmin Chen、Nouri Neamati

  DOI：10.1016/j.ejmech.2020.112387

  日期：2020.10

  The C-X-C motif ligand 8 and C-X-C chemokine receptor 2 (CXCL8-CXCR2) axis is involved in pathogenesis of various diseases including inflammation and cancers. Various CXCR2 antagonists are under development for several diseases. Our previous high-throughput cell-based assay specific for CXCR2 has identified a pyrimidine-based compound CX797 acting on CXCR2 down-stream signaling. A lead optimization campaign through scaffold-hopping strategy led to a series of 2-thioureidothiophene-3-carboxylates (TUTP) as novel CXCR2 antagonists. Structure-activity relationship study of TUTPs led to the identification of compound 52 that significantly inhibited CXCR2-mediated beta-arrestin recruitment signaling (IC50 = 1.1 +/- 0.01 mu M) with negligible effect on CXCL8-mediated cAMP signaling and calcium flux. Similar to the known CXCR2 antagonist SB265610, compound 52 inhibited CXCL8-CXCR2 induced phosphorylation of ERK1/2. TUTP compounds also inhibited CXCL8-mediated cell migration and showed synergy with doxorubicin in ovarian cancer cells, thereby supporting TUTPs as promising compounds for cancer treatment. (C) 2020 Elsevier Masson SAS. All rights reserved.