酪氨酸磷酸化抑制剂 | 122520-86-9

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - 酪氨酸类衍生物
• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 中文名称: 酪氨酸磷酸化抑制剂
• 英文名称: tyrphostin 47
• 英文别名: Tyrphostin A47；(E)-2-cyano-3-(3,4-dihydroxyphenyl)prop-2-enethioamide
• CAS: 122520-86-9
• 化学式: C₁₀H₈N₂O₂S
• 分子量: 220.252
• InChiKey: ZGHQGWOETPXKLY-XVNBXDOJSA-N

物化性质

• 熔点：
  213 °C
• 沸点：
  474.5±55.0 °C(Predicted)
• 密度：
  1.512±0.06 g/cm3(Predicted)
• 溶解度：
  DMSO：50 mg/mL，透明，橙色
• 稳定性/保质期：

  遵照规定使用和储存，则不会分解。

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  122
• 氢给体数：
  3
• 氢受体数：
  4

安全信息

• 危险品标志：
  Xi
• 安全说明：
  S26,S36
• 危险类别码：
  R36/37/38
• WGK Germany：
  3

反应信息

• 作为产物：
  描述：

  3,4-二羟基苯甲醛 、 2-氰基硫代乙酰胺 在 哌啶 作用下， 以 乙醇 为溶剂， 以41%的产率得到酪氨酸磷酸化抑制剂
  参考文献：
  名称：

  Tyrphostins I: synthesis and biological activity of protein tyrosine kinase inhibitors

  摘要：

  A novel class of low molecular weight protein tyrosine kinase inhibitors is described. These compounds constitute a systematic series of molecules with a progressive increase in affinity toward the substrate site of the EGF receptor kinase domain. These competitive inhibitors also effectively block the EGF-dependent autophosphorylation of the receptor. The potent EGF receptor kinase blockers examined were found to competitively inhibit the homologous insulin receptor kinase at 10(2)-10(3) higher inhibitor concentrations in spite of the significant homology between these protein tyrosine kinases. These results demonstrate the ability to synthesize selective tyrosine kinase inhibitors. The most potent EGF receptor kinase inhibitors also inhibit the EGF-dependent proliferation of A431/clone 15 cells with little or no effect on EGF independent cell growth. These results demonstrate the potential use of protein tyrosine kinase inhibitors as selective antiproliferative agents for proliferative diseases caused by the hyperactivity of protein tyrosine kinases. We have suggested the name "tyrphostins" for this class of antiproliferative compounds which act as protein tyrosine kinase blockers.

  DOI：

  10.1021/jm00130a020

文献信息

• COMPOSITIONS AND METHODS FOR THE TREATMENT OF PATHOLOGICAL CONDITION(S) RELATED TO GPR35 AND/OR GPR35-HERG COMPLEX
  申请人：Deng Huayun

  公开号：US20120022116A1

  公开（公告）日：2012-01-26

  Disclosed are compositions and methods for the prevention and/or treatment of diseases which are pathophysiologically related to GPR35, and/or GPR35-hERG signaling complex. For example, disclosed are compounds for preventing and/or treating diseases which are pathophysiologically related to GPR35 in a subject. The compounds having a formula (I), (II) or (III):

  揭示了与GPR35及/或GPR35-hERG信号复合物在病理生理上相关的疾病的预防和/或治疗的组合物和方法。例如，揭示了用于预防和/或治疗与GPR35在受试者中病理生理相关的疾病的化合物。这些化合物具有以下公式(I)、(II)或(III)：
• [EN] 2,6-BIS(((1H-BENZO[D]IMIDAZOL-2-YL)THIO)METHYL)PYRIDINE AND N2,N6-DIBENZYLPYRIDINE-2,6-DICARBOXAMIDE DERIVATIVES AND RELATED COMPOUNDS AS PHOSPHOINOSITIDE 3-KINASE (PI3K) INHIBITORS FOR TREATING CANCER<br/>[FR] DÉRIVÉS DE 2,6-BIS(((1H-BENZO[D]IMIDAZOL-2-YL)THIO)MÉTHYL)PYRIDINE ET DE N2,N6-DIBENZYLPYRIDINE-2,6-DICARBOXAMIDE ET COMPOSÉS ASSOCIÉS EN TANT QU'INHIBITEURS DE PHOSPHOINOSITIDE 3-KINASE (PI3K) DANS LE TRAITEMENT DU CANCER
  申请人：BIOMEDICAL RES FOUNDATION OF THE ACADEMY OF ATHENS BRFAA

  公开号：WO2020039097A1

  公开（公告）日：2020-02-27

  2,6-bis(((lH-benzo[d]imidazol-2-yl)thio)methyl)pyridine and N2, N6-dibenzylpyridine-2, 6-dicarboxamide derivatives and related compounds as phosphoinositide 3-kinase (PI3K) inhibitors for treating cancer. The present invention relates to pharmaceutically active 2,6- bis(((lH-benzo[d]imidazol-2-yl)thio)methyl)pyridine, N2,N6- dibenzylpyridine-2, 6-dicarboxamide and N2,N6-bis(3-hydroxyphenyl) pyridine-2, 6-dicarboxamide, as well as to derivatives thereof, and to structurally related compounds. These compounds are phosphoinositide 3-kinase inhibitors (PI3K) and useful in treating or preventing cancerous diseases. The invention further relates methods of manufacturing such compounds as well as to pharmaceutical compositions and formulations comprising such compounds, optionally together with other pharmaceutically active compounds. The invention further relates to a method for determining the activity of PI3Kalpha or PI3Kalpha mutants, which method includes: a) providing a solid phase which is functionalized by immobilization of GST-GRPl-molecules onto the solid phase, b) performing a PI3Kalpha or PI3Kalpha mutant catalyzed enzyme reaction to convert PIP2 to PIP3, c) adding competitor PIP3 carrying a detectable label or reporter molecule, and d) determining enzyme activity based on the amount of PIP3 obtained in step b) which competes with competitor PIP3 for binding to the functionalized solid phase.

  2,6-双(((1H-苯并[d]咪唑-2-基)硫)甲基)吡啶和N2，N6-二苄基吡啶-2,6-二甲酰胺衍生物及相关化合物作为治疗癌症的磷脂酰肌醇3-激酶（PI3K）抑制剂。本发明涉及具有药用活性的2,6-双(((1H-苯并[d]咪唑-2-基)硫)甲基)吡啶，N2，N6-二苄基吡啶-2,6-二甲酰胺和N2，N6-双(3-羟基苯基)吡啶-2,6-二甲酰胺，以及其衍生物和结构相关化合物。这些化合物是磷脂酰肌醇3-激酶抑制剂（PI3K），可用于治疗或预防癌症性疾病。本发明还涉及制造这类化合物的方法，以及包含这类化合物的药物组合物和配方，可选地与其他药用活性化合物一起使用。本发明还涉及一种确定PI3Kalpha或PI3Kalpha突变体活性的方法，该方法包括：a)提供通过将GST-GRPl分子固定在固相上而功能化的固相，b)执行PI3Kalpha或PI3Kalpha突变体催化的酶反应将PIP2转化为PIP3，c)添加携带可检测标签或报告分子的竞争物PIP3，d)根据步骤b)中获得的与竞争物PIP3竞争与功能化固相结合的PIP3的数量确定酶活性。
• [EN] NOVEL COMPOUNDS FOR USE IN TREATING OR PREVENTING CANCEROUS DISEASES<br/>[FR] NOUVEAUX COMPOSÉS UTILISABLES DANS LE TRAITEMENT OU LA PRÉVENTION DE MALADIES CANCÉREUSES
  申请人：BIOMEDICAL RES FOUND OF THE ACAD OF ATHENS

  公开号：WO2017005919A1

  公开（公告）日：2017-01-12

  The invention relates to new compounds of formula (I) that are useful in medicine, specifically in treating or preventing cancerous diseases in a mammal, to pharmaceutical compositions comprising such compounds, optionally together with other pharmaceutically active compounds, or to pharmaceutical formulations comprising such compounds or pharmaceutical compositions. The invention further relates to methods of making these compounds.

  本发明涉及公式（I）的新化合物，该化合物在医学上具有用途，特别是在哺乳动物中治疗或预防癌症性疾病，以及包含这些化合物的药物组合物，可选地与其他药物活性化合物一起，或包含这些化合物或药物组合物的药物制剂。本发明还涉及制备这些化合物的方法。
• Styryl compounds which inhibit EGF receptor protein tyrosine kinase
  申请人：Yissum Research Development Company of the Hebrew University of Jerusalem

  公开号：US05217999A1

  公开（公告）日：1993-06-08

  A method of inhibiting cell proliferation in a patient suffering from such disorder comprising administering to said patient an effective amount of a composition comprising, in admixture with a pharmaceutically acceptable carrier, a compound, or a pharmaceutically acceptable salt thereof, which is a substituted styrene compound which can also be a naphthalene, an indane or a benzoxazine; including nitrile and molononitrile compounds, and pharmaceutical compositions comprising, in admixture with a pharmaceutically acceptable carrier, a pharmaceutically-effective amount of such compound.

  一种抑制患有该疾病患者细胞增殖的方法，包括向该患者施用与药学上可接受的载体混合的有效量的组合物，所述组合物包括一种取代苯乙烯化合物，该化合物也可以是萘、茚、苯并噁嗪，包括腈和莫洛腈化合物，以及与药学上可接受的载体混合的药物组合物，其中包括该化合物的药学有效量。
• Methods and Agents for Inhibiting Dynamin-Dependent Endocytosis
  申请人：McCluskey Adam

  公开号：US20070225363A1

  公开（公告）日：2007-09-27

  There are disclosed methods for inhibiting dynamin-dependent endocytosis in cells comprising treating the cells with an effective amount of a compound of formula (I), or a dimeric tyrphostin, physiologically acceptable salt, or prodrug thereof. Compounds useful in the methods described are also provided. The inhibition of dynamin-dependent endocytosis of cells is applicable to the treatment of epilepsy and neurological disorders and conditions.

  本文揭示了抑制细胞中依赖于动力蛋白的内吞作用的方法，其中包括使用化合物(I)、二聚酪氨酸酪氨酸激酶抑制剂、生理可接受的盐或前药的有效量处理细胞。本文还提供了适用于所述方法的化合物。抑制细胞中依赖于动力蛋白的内吞作用适用于治疗癫痫和神经系统疾病和症状。