1-[4-氨基-7-(3-羟基丙基)-5-(4-甲基苯基)-7H-吡咯并[2,3-D]嘧啶-6-基]-2-氟乙酮 | 821794-92-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 中文名称: 1-[4-氨基-7-(3-羟基丙基)-5-(4-甲基苯基)-7H-吡咯并[2,3-D]嘧啶-6-基]-2-氟乙酮
• 英文名称: Fmk
• 英文别名: 1-[4-Amino-7-(3-hydroxypropyl)-5-(4-methylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-2-fluoroethanone；1-[4-amino-7-(3-hydroxypropyl)-5-(4-methylphenyl)pyrrolo[2,3-d]pyrimidin-6-yl]-2-fluoroethanone
• CAS: 821794-92-7
• 化学式: C₁₈H₁₉FN₄O₂
• 分子量: 342.373
• InChiKey: IKLGYJACVCXYIL-UHFFFAOYSA-N

物化性质

• 密度：
  1.36
• 溶解度：
  不溶于水； DMSO 中≥17.1 mg/mL；乙醇中≥28.7 mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  94
• 氢给体数：
  2
• 氢受体数：
  6

制备方法与用途

生物活性

FMK 是一种不可逆的 RSK2 抑制剂，能够共价修饰 RSK 的 C 末端区域。

体外研究

将 ARVMs 用 3 μM FMK 预处理可减轻 Ser386 磷酸化水平的增加，但对 Thr577 磷酸化水平的增加没有抑制作用。尽管 FMK 在测试的蛋白质激酶中仅抑制了少数几种，如 Src、Lck、Yes 和 Eph-A2 以及 S6K1，但它确实抑制了蛋白酪氨酸激酶。当 N-末端激酶结构域通过独立于 C-末端结构域的机制激活时，FMK 不会抑制 RSK。

在哺乳动物细胞中，FMK 高度特异地失活 RSK1 和 RSK2 的 CTD 自动磷酸化活性。用特定的小分子 RSK 抑制剂 FMK 靶向 RSK2 可减轻 FGFR3 引起的 Ba/F3 细胞无依赖性细胞因子生长。FMK 抑制由 FGFR3 介导的 Ba/F3 细胞无依赖性增殖。

反应信息

• 作为产物：
  描述：

  Ethanone, 1-[4-amino-7-[3-[[(1,1-dimethylethyl)dimethylsilyl]oxy]propyl]-5-(4-methylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-2-fluoro- 在 盐酸 、 碳酸氢钠 、 sodium chloride 作用下， 以 四氢呋喃 、 水 、 乙酸乙酯 为溶剂， 反应 3.0h， 生成 1-[4-氨基-7-(3-羟基丙基)-5-(4-甲基苯基)-7H-吡咯并[2,3-D]嘧啶-6-基]-2-氟乙酮
  参考文献：
  名称：

  WO2007/38613

  摘要：

  公开号：

文献信息

• METHOD FOR PRODUCING INSULIN-PRODUCING CELLS
  申请人：Kataoka Corporation

  公开号：EP3882339A1

  公开（公告）日：2021-09-22

  It is a main object of the present invention to provide a process for producing an insulin-producing cell from a somatic cell without performing artificial gene transfer, an insulin-producing cell obtained from the process, or a composition comprising a combination of chemical substances that can be used for the process. The present invention can include, for example: a process for producing an insulin-producing cell from a somatic cell by direct differentiation induction, comprising a step of culturing a somatic cell in the presence of an RSK inhibitor; an insulin-producing cell obtained from the process; and a composition for producing an insulin-producing cell from a somatic cell by directly inducing differentiation, comprising an RSK inhibitor. The insulin-producing cells obtained according to the present invention are useful in regenerative medicine and the like.

  本发明的主要目的是提供一种在不进行人工基因转移的情况下从体细胞制备胰岛素分泌细胞的工艺、从该工艺中获得的胰岛素分泌细胞或由可用于该工艺的化学物质组合而成的组合物。例如，本发明可包括：通过直接诱导分化从体细胞产生胰岛素分泌细胞的工艺，包括在 RSK 抑制剂存在下培养体细胞的步骤；从该工艺中获得的胰岛素分泌细胞；以及通过直接诱导分化从体细胞产生胰岛素分泌细胞的组合物，包括 RSK 抑制剂。根据本发明获得的胰岛素分泌细胞可用于再生医学等领域。
• METHOD FOR PRODUCING INSULIN-PRODUCING CELLS, AND COMPOSITION
  申请人：Kataoka Corporation

  公开号：EP3882340A1

  公开（公告）日：2021-09-22

  It is a main object of the present invention to provide a new producing method capable of efficiently performing direct conversion or induction from a somatic cell to an insulin-producing cell. The present invention can include, for example, a process for producing an insulin-producing cell by direct differentiation induction from a somatic cell, comprising a step of culturing a somatic cell in a serum-free differentiation induction medium, or a step of culturing a somatic cell in a differentiation induction medium containing 5 µg/mL or more of insulin. According to the present invention, insulin-producing cells having a high insulin secretion ability can be produced directly and efficiently from a somatic cell. The insulin-producing cells obtained according to the present invention are useful in regenerative medicine and the like.

  本发明的主要目的是提供一种新的生产方法，能够有效地将体细胞直接转化或诱导为胰岛素生产细胞。例如，本发明可包括通过从体细胞直接分化诱导产生胰岛素分泌细胞的工艺，包括在无血清分化诱导培养基中培养体细胞的步骤，或在含有 5 µg/mL 或更多胰岛素的分化诱导培养基中培养体细胞的步骤。根据本发明，可直接有效地从体细胞制备出具有高胰岛素分泌能力的胰岛素分泌细胞。根据本发明获得的胰岛素分泌细胞可用于再生医学等领域。
• Autophagy inducers for treatment of CNS conditions
  申请人：Northwestern University

  公开号：US11241436B2

  公开（公告）日：2022-02-08

  The invention provides a compound of formula (I): wherein R1, R2, R3, and R4 are as defined herein, ginsenoside Rg2 of structure (II): or a combination thereof, for use in treating or preventing a condition responsive to the induction of autophagy in a brain of a mammal in need thereof.

  本发明提供了一种式（I）：其中 R1、R2、R3 和 R4 如本文所定义的化合物，结构（II）：或其组合的人参皂苷 Rg2，用于治疗或预防需要其的哺乳动物大脑中对自噬诱导有反应的病症。
• METHODS OF TREATING CANCER WITH AN INHIBITOR OF ZNF827
  申请人：Children's Medical Research Institute

  公开号：EP3982977A1

  公开（公告）日：2022-04-20
• Selective serine/threonine kinase inhibitors
  申请人：Taunton Jack

  公开号：US20070082884A1

  公开（公告）日：2007-04-12

  Inhibition of protein kinases having one or more cysteine residues within the ATP binding site is effected by contacting the kinase, per se or in a cell or subject, with an inhibitory-effective amount of a compound having a heterocyclic core structure comprised of two or more fused rings containing at least one nitrogen ring atom, and an electrophilic substituent that is capable of reacting with a cysteine residue within the ATP binding site of a kinase. Preferred compounds include certain pyrrolopyrimidines and oxindoles having such an electrophilic substituent and optionally an aromatic or heteroaromatic substituent that is capable of interacting with a threonine or smaller residue located in the gatekeeper position of the kinase. Kinases lacking such cysteine residues may be engineered or modified so that they are capable of being inhibited by such compounds by replacing a valine or other amino acid residue within the ATP binding site by a cysteine residue.