H-89 Dihydrochloride

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: H-89 Dihydrochloride
• 英文别名: N-[2-[[(E)-3-(4-bromophenyl)prop-2-enyl]amino]ethyl]isoquinoline-5-sulfonamide;dihydrochloride
• 化学式: C20H22BrCl2N3O2S
• 分子量: 519.3
• InChiKey: GELOGQJVGPIKAM-WTVBWJGASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.42
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  79.5
• 氢给体数：
  4
• 氢受体数：
  5

文献信息

• NOOTROPIC AGENT
  申请人：DAIICHI PHARMACEUTICAL CO., LTD.

  公开号：EP1022029A1

  公开（公告）日：2000-07-26

  A drug which improves cerebral neurotransmission based on interaction of long-term activation of a protein kinase C pathway and long-term activation of presynaptic nicotinic acetylcholine (nACh) receptors, and on an accompanying increase in the amount of released glutamate, which activates cerebral neurotransmission over a prolonged period. The substances of the present invention serve as excellent nootropics. They are particularly useful for the therapy of dementia caused by hydrocephalus, or by subdural hemorrhage.

  一种基于长期激活蛋白激酶 C 途径和长期激活突触前烟碱乙酰胆碱（nACh）受体的相互作用，以及伴随的谷氨酸释放量的增加而改善脑神经递质的药物，可长期激活脑神经递质。本发明的物质是一种极好的促智剂。它们尤其适用于治疗由脑积水或硬脑膜下出血引起的痴呆症。
• METHOD OF PRODUCING PANCREATIC HORMONE-PRODUCING CELLS
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP2604685A1

  公开（公告）日：2013-06-19

  The present invention aims to provide a production method of pancreatic hormone-producing cells in a form more mimicking the pancreatogenesis. A method of producing pancreatic hormone-producing cells, comprising subjecting stem cells to the following steps (1) - (6) : (1) a step of cultivating stem cells in a medium containing a Rho kinase inhibitor (2) a step of cultivating the cells obtained in the aforementioned step (1) in a medium containing a GSK3 inhibitor (3) a step of cultivating the cells obtained in the aforementioned step (2) in a medium containing GSK3 inhibitor and an activator of activin receptor-like kinase-4,7 (4) a step of forming a cell mass from the cells obtained in the aforementioned (3), and cultivating the cell mass in a suspension state in a medium (5) a step of cultivating the cells obtained in the aforementioned step (4) in a medium containing a retinoic acid receptor agonist, an inhibitor of AMP-activated protein kinase and/or activin receptor-like kinase-2,3,6, an inhibitor of activin receptor-like kinase-4,5,7 and a cell growth factor (6) a step of cultivating the cells obtained in the aforementioned step (5).

  本发明旨在提供一种生产胰腺激素分泌细胞的方法，其形式更模拟胰腺的生成。 一种生产胰腺激素产生细胞的方法，包括使干细胞经受以下步骤(1)-(6)： (1) 在含有 Rho 激酶抑制剂的培养基中培养干细胞的步骤 (2) 在含有 GSK3 抑制剂的培养基中培养上述步骤(1)中获得的细胞的步骤 (3) 在含有 GSK3 抑制剂和活化素受体样激酶激活剂-4,7 的培养基中培养上述步骤（2）中获得的细胞的步骤 (4) 将上述步骤(3)中获得的细胞形成细胞团，并在培养基中以悬浮状态培养该细胞团的步骤 (5) 在含有维甲酸受体激动剂、AMP 活化蛋白激酶和/或活化因子受体样激酶-2,3,6 的抑制剂、活化因子受体样激酶-4,5,7 的抑制剂和细胞生长因子的培养基中培养上述步骤（4）中获得的细胞的步骤 (6) 培养上述步骤（5）中获得的细胞。
• METHOD FOR PRODUCING CORNEAL ENDOTHELIAL CELL
  申请人：Keio University

  公开号：EP2765188A1

  公开（公告）日：2014-08-13

  The present invention aims to provide a method of efficiently producing corneal endothelial cells, particularly from corneal stroma or iPS cell-derived neural crest stem cells, a method of producing corneal endothelial cells stably in a large amount by inducing more efficient differentiation of stem cells into corneal endothelial cells, and a medicament containing corneal endothelial cells. A method of inducing differentiation of stem cells into corneal endothelial cells, which includes a step of culturing the stem cells in a differentiation induction medium containing a GSK3 inhibitor (preferably a GSK3β inhibitor) and retinoic acid, preferably the differentiation induction medium further containing at least one kind selected from the group consisting of TGFb2, insulin and a ROCK inhibitor, and the like.

  本发明旨在提供一种高效生产角膜内皮细胞的方法，特别是由角膜基质或iPS细胞衍生的神经嵴干细胞生产角膜内皮细胞的方法，一种通过诱导干细胞更有效地分化为角膜内皮细胞而大量稳定生产角膜内皮细胞的方法，以及一种含有角膜内皮细胞的药物。 一种诱导干细胞分化为角膜内皮细胞的方法，它包括在含有GSK3抑制剂（最好是GSK3β抑制剂）和维甲酸的分化诱导培养基中培养干细胞的步骤，最好是分化诱导培养基进一步含有至少一种选自TGFb2、胰岛素和ROCK抑制剂等组成的组的物质。
• MK2/3 INHIBITORS TO TREAT METABOLIC DISTURBANCES OF OBESITY
  申请人：The Trustees of Columbia University in the City of New York

  公开号：EP3072555A1

  公开（公告）日：2016-09-28

  The present invention relates to methods of treating or preventing a metabolic disorder in a subject, methods of treating or preventing coronorary artery disease in a subject with a metabolic disorder, as well as methods of reducing hepatic glucose production in a subject. Such methods include, but are not limited to, the administration to the subject of inhibitors of CaMKII, IP3Rs, calcineurin, p38, MK2/3, or any combination thereof. The invention also provides methods of identifying a compound that inhibits the activity of CaMKII, IP3Rs, calcineurin, p38, or MK2/3, or reduces the activity and/or activation of CaMKII, IP3Rs, calcineurin, p38, or MK2/3.

  本发明涉及治疗或预防受试者代谢紊乱的方法，治疗或预防代谢紊乱受试者冠状动脉疾病的方法，以及减少受试者肝糖生成的方法。这些方法包括但不限于向受试者施用 CaMKII、IP3Rs、钙神经蛋白、p38、MK2/3 或其任意组合的抑制剂。本发明还提供了鉴定抑制 CaMKII、IP3Rs、钙调磷酸酶、p38 或 MK2/3 活性，或降低 CaMKII、IP3Rs、钙调磷酸酶、p38 或 MK2/3 活性和/或活化的化合物的方法。
• METHOD FOR PRODUCING THERAPEUTIC CORNEAL ENDOTHELIAL SUBSTITUTE CELL SPHERE
  申请人：Keio University

  公开号：EP3231863A1

  公开（公告）日：2017-10-18

  The problem of the present invention is to provide a method of efficiently producing therapeutic alternative corneal endothelial cells, particularly, a method capable of stably producing them in a condition suitable for intraocular transplantation (in the anterior chamber) in a large amount. Furthermore, the present invention aims to provide a composition for transplantation, which is preferable for intraocular administration, particularly, into the anterior chamber. A therapeutic alternative corneal endothelial cell sphere can be produced by culturing stem cells in suspension in a differentiation induction medium containing a GSK3 inhibitor, retinoic acid and a ROCK inhibitor. Addition of a viscoelastic substance during intraocular (into the anterior chamber) transplantation of the sphere or cultured corneal endothelial cells dispersed into single cells can increase the number of adherent cells after transplantation.

  本发明的问题是提供一种高效生产治疗性替代角膜内皮细胞的方法，特别是一种能够在适合眼内移植（前房）的条件下大量稳定生产角膜内皮细胞的方法。此外，本发明旨在提供一种用于移植的组合物，该组合物最好用于眼内给药，特别是用于前房。通过在含有 GSK3 抑制剂、维甲酸和 ROCK 抑制剂的分化诱导培养基中培养悬浮干细胞，可生产出治疗性替代角膜内皮细胞球。在眼内（前房）移植球体或分散成单细胞的培养角膜内皮细胞时，加入粘弹性物质可增加移植后附着细胞的数量。