N-(3-(4-methoxybenzyloxy)phenyl)-2-(3-(morpholinomethyl)phenyl)thieno[3,2-b]pyridin-7-amine | 1228103-44-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并吡啶类
• 英文名称: N-(3-(4-methoxybenzyloxy)phenyl)-2-(3-(morpholinomethyl)phenyl)thieno[3,2-b]pyridin-7-amine
• 英文别名: N-[3-[(4-methoxyphenyl)methoxy]phenyl]-2-[3-(morpholin-4-ylmethyl)phenyl]thieno[3,2-b]pyridin-7-amine
• CAS: 1228103-44-3
• 化学式: C₃₂H₃₁N₃O₃S
• 分子量: 537.682
• InChiKey: HIEOKPHEZZCGSL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  39
• 可旋转键数：
  9
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  84.1
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-(3-(4-methoxybenzyloxy)phenyl)-2-(3-(morpholinomethyl)phenyl)thieno[3,2-b]pyridin-7-amine 在 盐酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 15.0h， 以99%的产率得到3-(2-(3-(morpholinomethyl)phenyl)thieno[3,2-b]pyridine-7-ylamino)phenol
  参考文献：
  名称：

  LCB 03-0110, a Novel Pan-Discoidin Domain Receptor/c-Src Family Tyrosine Kinase Inhibitor, Suppresses Scar Formation by Inhibiting Fibroblast and Macrophage Activation

  摘要：

  伤口愈合通常会引起炎症反应，并伴有组织纤维化，其中活化的巨噬细胞和肌成纤维细胞是主要参与者。虽然这是疤痕和各种纤维化病理的基础机制，但目前尚无有效的干预措施。我们发现了噻吩并吡啶衍生物（3-(2-(3-(吗啉甲基)苯基)噻吩[3,2-b]吡啶-7-基氨基)苯酚（LCB 03-0110）是盘状蛋白结构域受体家族酪氨酸激酶的强效抑制剂，并发现该化合物可强烈抑制多种酪氨酸激酶，包括c-Src家族、脾酪氨酸激酶、布鲁顿酪氨酸激酶和血管内皮生长因子受体2，这些激酶对于免疫细胞信号传导和炎症反应至关重要。LCB 03-0110抑制

  DOI：

  10.1124/jpet.111.187328
• 作为产物：
  描述：

  吗啉 、 3-(7-(3-(4-methoxybenzyloxy)phenylamino)thieno[3,2-b]pyridin-2-yl)benzaldehyde 在 sodium acetate 、 三乙酰氧基硼氢化钠 作用下， 以 二氯甲烷 为溶剂， 反应 5.33h， 以48%的产率得到N-(3-(4-methoxybenzyloxy)phenyl)-2-(3-(morpholinomethyl)phenyl)thieno[3,2-b]pyridin-7-amine
  参考文献：
  名称：

  LCB 03-0110, a Novel Pan-Discoidin Domain Receptor/c-Src Family Tyrosine Kinase Inhibitor, Suppresses Scar Formation by Inhibiting Fibroblast and Macrophage Activation

  摘要：

  伤口愈合通常会引起炎症反应，并伴有组织纤维化，其中活化的巨噬细胞和肌成纤维细胞是主要参与者。虽然这是疤痕和各种纤维化病理的基础机制，但目前尚无有效的干预措施。我们发现了噻吩并吡啶衍生物（3-(2-(3-(吗啉甲基)苯基)噻吩[3,2-b]吡啶-7-基氨基)苯酚（LCB 03-0110）是盘状蛋白结构域受体家族酪氨酸激酶的强效抑制剂，并发现该化合物可强烈抑制多种酪氨酸激酶，包括c-Src家族、脾酪氨酸激酶、布鲁顿酪氨酸激酶和血管内皮生长因子受体2，这些激酶对于免疫细胞信号传导和炎症反应至关重要。LCB 03-0110抑制

  DOI：

  10.1124/jpet.111.187328

文献信息

• ANTI-INFLAMMATORY COMPOUND HAVING INHIBITORY ACTIVITY AGAINST MULTIPLE TYROSINE KINASES AND PHARMACEUTICAL COMPOSITION CONTAINING SAME
  申请人：Yang Beom-Seok

  公开号：US20130072482A1

  公开（公告）日：2013-03-21

  The present invention is for the anti-inflammatory compounds that have an inhibitory activity against protein tyrosine kinases and their pharmaceutical composition(s) containing the compound as the active ingredient. Since the compounds of the present invention can inhibit multiple protein kinases associated with inflammatory diseases and immune disorders, they are useful for their prevention or treatment.

  本发明涉及具有抑制蛋白酪氨酸激酶活性的抗炎化合物及其含有该化合物作为活性成分的药物组合物。由于本发明的化合物可以抑制与炎症性疾病和免疫紊乱相关的多种蛋白激酶，因此它们对于预防或治疗这些疾病是有用的。
• ANTI-INFLAMMATORY COMPOUND HAVING INHIBITORY ACTIVITY AGAINST MULTIPLE TYROSINE KINASES, AND PHARMACEUTICAL COMPOSITION CONTAINING SAME
  申请人：Korea Institute of Science and Technology

  公开号：EP2578590A2

  公开（公告）日：2013-04-10

  The present invention is for the anti-inflammatory compounds that have an inhibitory activity against protein tyrosine kinases and their pharmaceutical composition(s) containing the compound as the active ingredient. Since the compounds of the present invention can inhibit multiple protein kinases associated with inflammatory diseases and immune disorders, they are useful for their prevention or treatment.

  本发明涉及对蛋白酪氨酸激酶具有抑制活性的抗炎化合物及其含有该化合物作为活性成分的药物组合物。由于本发明的化合物可抑制与炎症性疾病和免疫紊乱有关的多种蛋白激酶，因此可用于预防或治疗这些疾病。
• EP2578590B1
  申请人：——

  公开号：EP2578590B1

  公开（公告）日：2017-08-16
• US9062066B2
  申请人：——

  公开号：US9062066B2

  公开（公告）日：2015-06-23
• LCB 03-0110, a Novel Pan-Discoidin Domain Receptor/c-Src Family Tyrosine Kinase Inhibitor, Suppresses Scar Formation by Inhibiting Fibroblast and Macrophage Activation
  作者：Xiaoyan Sun、Trong Nhat Phan、Seung Hee Jung、Sun Young Kim、Jong Un Cho、Hyangsook Lee、Sung Ho Woo、Tae Kyo Park、Beom-Seok Yang

  DOI：10.1124/jpet.111.187328

  日期：2012.3

  Wound healing generally induces an inflammatory response associated with tissue fibrosis in which activated macrophage and myofibroblast cells are primarily involved. Although this is known to be the underlying mechanism for scarring and various fibrotic pathologies, no effective intervention is currently available. We identified (3-(2-(3-(morpholinomethyl)phenyl)thieno[3,2-b]pyridin-7-ylamino)phenol (LCB 03-0110), a thienopyridine derivative, as a potent inhibitor of discoidin domain receptor family tyrosine kinases and discovered that this compound strongly inhibits several tyrosine kinases, including the c-Src family, spleen tyrosine kinase, Bruton's tyrosine kinase, and vascular endothelial growth factor receptor 2, which are important for immune cell signaling and inflammatory reactions. LCB 03-0110 suppressed the proliferation and migration of primary dermal fibroblasts induced by transforming growth factor β1 and type I collagen, and this result correlated with the inhibition ability of the compound against enhanced expression of α-smooth muscle actin and activation of Akt1 and focal adhesion kinase. In J774A.1 macrophage cells activated by lipopolysaccharide LCB 03-0110 inhibited cell migration and nitric oxide, inducible nitric-oxide synthase, cyclooxygenase 2, and tumor necrosis factor-α synthesis. LCB 03-0110 applied topically to full excisional wounds on rabbit ears suppressed the accumulation of myofibroblast and macrophage cells in the healing wound and reduced hypertrophic scar formation after wound closing, without delaying the wound closing process. Taken together, the pharmacological activities of LCB 03-0110 suggest that it could be an effective agent for suppressing fibroinflammation by simultaneously targeting activated fibroblasts and macrophages.

  伤口愈合通常会引起炎症反应，并伴有组织纤维化，其中活化的巨噬细胞和肌成纤维细胞是主要参与者。虽然这是疤痕和各种纤维化病理的基础机制，但目前尚无有效的干预措施。我们发现了噻吩并吡啶衍生物（3-(2-(3-(吗啉甲基)苯基)噻吩[3,2-b]吡啶-7-基氨基)苯酚（LCB 03-0110）是盘状蛋白结构域受体家族酪氨酸激酶的强效抑制剂，并发现该化合物可强烈抑制多种酪氨酸激酶，包括c-Src家族、脾酪氨酸激酶、布鲁顿酪氨酸激酶和血管内皮生长因子受体2，这些激酶对于免疫细胞信号传导和炎症反应至关重要。LCB 03-0110抑制