LDN193189 | 1062368-39-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: LDN193189
• 英文别名: 4-[6-(4-piperazin-1-ylphenyl)pyrazolo[1,5-a]pyridin-3-yl]-quinoline；4-[6-[4-(1-Piperazinyl)phenyl]pyrazolo[1,5-a]pyridin-3-yl]quinoline；4-[6-(4-piperazin-1-ylphenyl)pyrazolo[1,5-a]pyridin-3-yl]quinoline
• CAS: 1062368-39-1
• 化学式: C₂₆H₂₃N₅
• 分子量: 405.502
• InChiKey: HMVOWZJWAKWRRX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  31
• 可旋转键数：
  3
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  45.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  N-Boc-4-[6-(4-piperazin-1-ylphenyl)pyrazolo[1,5-a]pyridin-3-yl]-quinoline 在 盐酸 、 甲醇 作用下， 以 1,4-二氧六环 为溶剂， 以12%的产率得到LDN193189
  参考文献：
  名称：

  [EN] INHIBITORS OF THE BMP SIGNALING PATHWAY
  [FR] INHIBITEURS DE LA VOIE DE SIGNALISATION BMP

  摘要：

  本发明提供了BMP信号通路的小分子抑制剂。这些化合物可用于调节细胞生长、分化、增殖和凋亡，因此可用于治疗与BMP信号通路相关的疾病或症状，包括炎症、心血管疾病、血液学疾病、癌症和骨骼疾病，以及调节细胞分化和/或增殖。

  公开号：

  WO2009114180A1

文献信息

• INHIBITORS OF THE BMP SIGNALING PATHWAY
  申请人：Yu Paul B.

  公开号：US20110053930A1

  公开（公告）日：2011-03-03

  The present invention provides small molecule inhibitors of BMP signaling. These compounds may be used to modulate cell growth, differentiation, proliferation, and apoptosis, and thus may be useful for treating diseases or conditions associated with BMP signaling, including inflammation, cardiovascular disease, hematological disease, cancer, and bone disorders, as well as for modulating cellular differentiation and/or proliferation.

  本发明提供了BMP信号通路的小分子抑制剂。这些化合物可以用于调节细胞生长、分化、增殖和凋亡，因此可能有用于治疗与BMP信号通路相关的疾病或病症，包括炎症、心血管疾病、血液疾病、癌症和骨骼疾病，以及调节细胞分化和/或增殖。
• METHOD FOR INDUCING DIFFERENTIATION OF INSULIN-PRODUCING CELLS
  申请人：Tokyo Institute of Technology

  公开号：EP3147356A1

  公开（公告）日：2017-03-29

  It is an object of the present invention to provide a method for efficiently directing differentiation into insulin-producing cells in a xeno-free culture system. According to the present invention, there is provided a method for directed differentiation into insulin-producing cells, comprising culturing stem cells in the following steps (1) to (5): (1) a step of culturing stem cells in a medium comprising an activator of activin receptor-like kinase-4/-7 and a GSK3 inhibitor and then culturing in a medium comprising an activator of activin receptor-like kinase-4/-7; (2) a step of culturing the cells obtained in step (1) in a medium comprising a hedgehog signaling inhibitor and an FGF; (3) a step of culturing the cells obtained in step (2) in a medium comprising a retinoic acid receptor agonist, a hedgehog signaling inhibitor and a BMP signaling inhibitor; (4) a step of culturing the cells obtained in step (3) in a medium comprising a TGF-β type I activin receptor-like kinase-4/-5/-7 inhibitor and a BMP signaling inhibitor; and (5) a step of culturing the cells obtained in step (4) in a medium comprising a phosphodiesterase inhibitor.

  本发明的目的是提供一种在无异种培养体系中有效引导分化成胰岛素分泌细胞的方法。根据本发明，提供了一种定向分化为胰岛素分泌细胞的方法，包括按以下步骤（1）至（5）培养干细胞：(1)在含有活化素受体样激酶-4/-7激活剂和GSK3抑制剂的培养基中培养干细胞，然后在含有活化素受体样激酶-4/-7激活剂的培养基中培养；(2)在含有刺猬信号转导抑制剂和FGF的培养基中培养步骤(1)中获得的细胞；(3) 在含有维甲酸受体激动剂、刺猬信号抑制剂和 BMP 信号抑制剂的培养基中培养步骤(2)中获得的细胞； (4) 在含有 TGF-β I 型激活素受体样激酶-4/-5/-7 抑制剂和 BMP 信号抑制剂的培养基中培养步骤(3)中获得的细胞；以及 (5) 在含有磷酸二酯酶抑制剂的培养基中培养步骤(4)中获得的细胞。
• Treating soft tissue via controlled drug release
  申请人：University of Pittsburgh—Of the Commonwealth System of Higher Education

  公开号：US10179111B2

  公开（公告）日：2019-01-15

  Methods for inhibiting tissue ossification or calcification in a subject, comprising administering a therapeutically effective amount of BMP I inhibitor-loaded microparticles to a subject in need thereof, wherein the administration provides local and sustained release of the BMP I inhibitor thereby inhibiting tissue ossification or calcification.

  抑制受试者组织骨化或钙化的方法，包括向有需要的受试者施用治疗有效量的 BMP I 抑制剂负载微粒，其中施用可提供 BMP I 抑制剂的局部和持续释放，从而抑制组织骨化或钙化。
• Method for inducing differentiation of insulin-producing cells
  申请人：TOKYO INSTITUTE OF TECHNOLOGY

  公开号：US10457916B2

  公开（公告）日：2019-10-29

  It is an object of the present invention to provide a method for efficiently directing differentiation into insulin-producing cells in a xeno-free culture system. According to the present invention, there is provided a method for directed differentiation into insulin-producing cells, comprising culturing stem cells in the following steps (1) to (5): (1) a step of culturing stem cells in a medium comprising an activator of activin receptor-like kinase-4/-7 and a GSK3 inhibitor and then culturing in a medium comprising an activator of activin receptor-like kinase-4/-7; (2) a step of culturing the cells obtained in step (1) in a medium comprising a hedgehog signaling inhibitor and an FGF; (3) a step of culturing the cells obtained in step (2) in a medium comprising a retinoic acid receptor agonist, a hedgehog signaling inhibitor and a BMP signaling inhibitor; (4) a step of culturing the cells obtained in step (3) in a medium comprising a TGF-β type I activin receptor-like kinase-4/-5/-7 inhibitor and a BMP signaling inhibitor; and (5) a step of culturing the cells obtained in step (4) in a medium comprising a phosphodiesterase inhibitor.

  本发明的目的是提供一种在无异种培养体系中有效引导分化成胰岛素分泌细胞的方法。根据本发明，提供了一种定向分化为胰岛素分泌细胞的方法，包括按以下步骤（1）至（5）培养干细胞：(1)在含有活化素受体样激酶-4/-7激活剂和GSK3抑制剂的培养基中培养干细胞，然后在含有活化素受体样激酶-4/-7激活剂的培养基中培养；(2)在含有刺猬信号转导抑制剂和FGF的培养基中培养步骤(1)中获得的细胞；(3) 在含有维甲酸受体激动剂、刺猬信号抑制剂和 BMP 信号抑制剂的培养基中培养步骤(2)中获得的细胞； (4) 在含有 TGF-β I 型激活素受体样激酶-4/-5/-7 抑制剂和 BMP 信号抑制剂的培养基中培养步骤(3)中获得的细胞；以及 (5) 在含有磷酸二酯酶抑制剂的培养基中培养步骤(4)中获得的细胞。
• Structure–activity relationship study of bone morphogenetic protein (BMP) signaling inhibitors
  作者：Gregory D. Cuny、Paul B. Yu、Joydev K. Laha、Xuechao Xing、Ji-Feng Liu、Carol S. Lai、Donna Y. Deng、Chetana Sachidanandan、Kenneth D. Bloch、Randall T. Peterson

  DOI：10.1016/j.bmcl.2008.06.052

  日期：2008.8

  A structure-activity relationship study of dorsomorphin, a previously identified inhibitor of SMAD 1/5/8 phosphorylation by bone morphogenetic protein (BMP) type 1 receptors ALK2, 3, and 6, revealed that increased inhibitory activity could be accomplished by replacing the pendent 4-pyridine ring with 4-quinoline. The activity contributions of various nitrogen atoms in the core pyrazolo[1,5-a]pyrimidine ring were also examined by preparing and evaluating pyrrolo[1,2-a] pyrimidine and pyrazolo[1,5-a] pyridine derivatives. In addition, increased mouse liver microsome stability was achieved by replacing the ether substituent on the pendent phenyl ring with piperazine. Finally, an optimized compound 13 (LDN-193189 or DM-3189) demonstrated moderate pharmacokinetic characteristics (e.g., plasma t(1/2) = 1.6 h) following intraperitoneal administration in mice. These studies provide useful molecular probes for examining the in vivo pharmacology of BMP signaling inhibition. (c) 2008 Elsevier Ltd. All rights reserved.