CYM-5478 | 870762-83-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: CYM-5478
• 英文别名: 1-[2-(1-Benzyl-2,5-dimethylpyrrol-3-yl)-2-oxoethyl]-5-(trifluoromethyl)pyridin-2-one
• CAS: 870762-83-7
• 化学式: C₂₁H₁₉F₃N₂O₂
• 分子量: 388.389
• InChiKey: RGSGTUIDJXHTTO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  42.3
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  CYM-5478 、 1-((4-azido)phenylthio)pyrrolidine-2,5-dione 在 2-((-2-(3-(3,5-bis(trifluoromethyl)phenyl)thioureido)cyclohexyl)carbamoyl)-3,4,5,6-tetrachlorobenzoic acid 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 48.0h， 以62%的产率得到1-(2-(4-((4-azidophenyl)thio)-1-benzyl-2,5-dimethyl-1H-pyrrol-3-yl)-2-oxoethyl)-5-(trifluoromethyl)pyridin-2(1H)-one
  参考文献：
  名称：

  A conjugate Lewis base-Brønsted acid catalyst for the sulfenylation of nitrogen containing heterocycles under mild conditions

  摘要：

  一种新的Lewis碱/Brønsted酸方法允许在极其温和的条件下对N-杂环化合物进行磺化。

  DOI：

  10.1039/c6cc09998j
• 作为产物：
  描述：

  1-(1-benzyl-2,5-dimethyl-1H-pyrrol-3-yl)-2-chloroethan-1-one 、 2-羟基-5-三氟甲基吡啶 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 以27%的产率得到CYM-5478
  参考文献：
  名称：

  A sphingosine 1-phosphate receptor 2 selective allosteric agonist

  摘要：

  Molecular probe tool compounds for the Sphingosine 1-phosphate receptor 2 (S1PR2) are important for investigating the multiple biological processes in which the S1PR2 receptor has been implicated. Amongst these are NF-kappa B-mediated tumor cell survival and fibroblast chemotaxis to fibronectin. Here we report our efforts to identify selective chemical probes for S1PR2 and their characterization. We employed high throughput screening to identify two compounds which activate the S1PR2 receptor. SAR optimization led to compounds with high nanomolar potency. These compounds, XAX-162 and CYM-5520, are highly selective and do not activate other SIP receptors. Binding of CYM-5520 is not competitive with the antagonist JTE-013. Mutation of receptor residues responsible for binding to the zwitterionic headgroup of sphingosine 1-phosphate (S1P) abolishes S1P activation of the receptor, but not activation by CYM-5520. Competitive binding experiments with radiolabeled S1P demonstrate that CYM-5520 is an allosteric agonist and does not displace the native ligand. Computational modeling suggests that CYM-5520 binds lower in the orthosteric binding pocket, and that co-binding with SIP is energetically well tolerated. In summary, we have identified an allosteric S1PR2 selective agonist compound. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.06.012

文献信息

• PHARMACEUTICAL COMPOSITION INCLUDING MIGRATORY FACTOR FOR GUIDING PLURIPOTENT STEM CELLS TO INJURY
  申请人：Clio, Inc.

  公开号：EP2962698A1

  公开（公告）日：2016-01-06

  The purpose of the present invention is to identify a migratory factor that guides pluripotent stem cells (Muse cells) useful in new medical applications to damage, and to provide a pharmaceutical composition that includes the migratory factor for promoting tissue regeneration in regenerative medicine that makes use of Muse cells. In the present invention, a receptor that is specifically expressed in Muse cells rather than non-Muse cells was identified, and it was confirmed that a ligand for this receptor can function as a migratory factor. In the present invention, sphingosine-1-phosphate (S1P) was identified as a migratory factor, and thus, the present invention pertains to a pharmaceutical composition for guiding pluripotent stem cells to damage, the composition including SIP as an active ingredient.

  本发明的目的是鉴定一种可引导多能干细胞（缪斯细胞）在新的医疗应用中发挥作用的迁移因子，并提供一种包含该迁移因子的药物组合物，用于促进再生医学中利用缪斯细胞的组织再生。在本发明中，确定了一种在缪斯细胞而非非缪斯细胞中特异表达的受体，并证实该受体的配体可作为迁移因子发挥作用。在本发明中，鞘氨醇-1-磷酸（S1P）被确定为一种迁移因子，因此，本发明涉及一种用于引导多能干细胞受损的药物组合物，该组合物包括作为活性成分的SIP。
• Pharmaceutical composition including migratory factor for guiding pluripotent stem cells to damage
  申请人：CLIO, INC.

  公开号：US10034889B2

  公开（公告）日：2018-07-31

  The purpose of the present invention is to identify a migratory factor that guides pluripotent stem cells (Muse cells) useful in new medical applications to damage, and to provide a pharmaceutical composition that includes the migratory factor for promoting tissue regeneration in regenerative medicine that makes use of Muse cells. In the present invention, a receptor that is specifically expressed in Muse cells rather than non-Muse cells was identified, and it was confirmed that a ligand for this receptor can function as a migratory factor. In the present invention, sphingosine-1-phosphate (S1P) was identified as a migratory factor, and thus, the present invention pertains to a pharmaceutical composition for guiding pluripotent stem cells to damage, the composition including S1P as an active ingredient.

  本发明的目的是鉴定一种可引导多能干细胞（缪斯细胞）在新的医疗应用中发挥作用的迁移因子，并提供一种包含该迁移因子的药物组合物，用于促进再生医学中利用缪斯细胞的组织再生。在本发明中，确定了一种在缪斯细胞而非非缪斯细胞中特异表达的受体，并证实该受体的配体可作为迁移因子发挥作用。在本发明中，鞘氨醇-1-磷酸（S1P）被确定为一种迁移因子，因此，本发明涉及一种引导多能干细胞受损的药物组合物，该组合物包括作为活性成分的S1P。
• PHARMACEUTICAL COMPOSITION INCLUDING MIGRATORY FACTOR FOR GUIDING PLURIPOTENT STEM CELLS TO DAMAGE
  申请人：CLIO INC.

  公开号：US20160354393A1

  公开（公告）日：2016-12-08

  The purpose of the present invention is to identify a migratory factor that guides pluripotent stem cells (Muse cells) useful in new medical applications to damage, and to provide a pharmaceutical composition that includes the migratory factor for promoting tissue regeneration in regenerative medicine that makes use of Muse cells. In the present invention, a receptor that is specifically expressed in Muse cells rather than non-Muse cells was identified, and it was confirmed that a ligand for this receptor can function as a migratory factor. In the present invention, sphingosine-1-phosphate (S1P) was identified as a migratory factor, and thus, the present invention pertains to a pharmaceutical composition for guiding pluripotent stem cells to damage, the composition including S1P as an active ingredient.
• US9446033B2
  申请人：——

  公开号：US9446033B2

  公开（公告）日：2016-09-20
• [DE] VERWENDUNG VON MODULATOREN DER SPHINGOSIN-1-PHOSPHAT-SIGNALTRANSDUKTION<br/>[EN] USE OF SPHINGOSINE-1-PHOSPHATE SIGNAL TRANSDUCTION MODULATORS<br/>[FR] UTILISATION DE MODULATEURS DE LA TRANSDUCTION DU SIGNAL DE LA SPHINGOSINE-1-PHOSPHATE
  申请人：UNIV DUISBURG ESSEN

  公开号：WO2019170796A1

  公开（公告）日：2019-09-12

  Die Erfindung betrifft die Verwendung eines Modulators der Sphingosin-1-phosphat-Signaltransduktion zur Herstellung eines Arzneimittels zur Behandlung einer Erkrankung oder Störung, die mit Sphingosin-1-phosphat und dessen Rezeptoren im Zusammenhang steht, wobei die Erkrankung oder Störung ausgewählt ist aus der Gruppe umfassend Erkrankungen oder Störungen des Knochengewebes, des Fettgewebes und/oder des Glukose-Stoffwechsels, sowie entsprechende Arzneimittel.