RG 13022 | 136831-48-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: RG 13022
• 英文别名: 3-(3,4-Dimethoxyphenyl)-2-(3-pyridinyl)-2-propenenitrile；3-(3,4-dimethoxyphenyl)-2-pyridin-3-ylprop-2-enenitrile
• CAS: 136831-48-6
• 化学式: C₁₆H₁₄N₂O₂
• 分子量: 266.299
• InChiKey: DBGZNJVTHYFQJI-UHFFFAOYSA-N

物化性质

• 熔点：
  116.0 to 120.0 °C
• 沸点：
  423.8±45.0 °C(Predicted)
• 密度：
  1.172±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于DMSO或乙醇：可溶
• 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)：
  2.6
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  55.1
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• WGK Germany：
  3
• 安全说明：
  S22,S24/25
• 危险性防范说明：
  P261,P280,P301+P312,P302+P352,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  存储于-20°C阴凉干燥处。

制备方法与用途

生物活性

RG 13022 (Tyrphostin RG13022)抑制免疫沉淀反应中EGF receptor的自磷酸化，IC50值为4 µM。

靶点

Target	Value
EGFR	4 μM

体外研究

RG13022能抑制由EGF刺激引起的癌细胞增殖。在无细胞反应中，它能够抑制免疫沉淀物中EGF受体的自磷酸化，IC50值为4 µM。RG13022以剂量依赖的方式抑制HER 14细胞通过50 ng/mL EGF的集落形成和DNA合成，其IC50值分别为1 μM和3 μM。此外，RG-13022不仅能抑制EGF诱导的生长，还能抑制由胰岛素、胰岛素样生长因子I、胰岛素样生长因子II或转化生长因子α刺激引起的生长。研究还表明，RG-13022可以完全阻断雌激素诱导的EGF受体磷酸化及雌激素介导的细胞增殖，这提示活性酪氨酸激酶（TK）途径对于雌激素作用是必需的。

体内研究

RG13022能抑制裸鼠肿瘤的生长，并延长这些携带肿瘤的裸鼠的寿命。

反应信息

• 作为产物：
  描述：

  3-吡啶乙腈 、 3,4-二甲氧基苯甲醛 在 哌啶 作用下， 以 乙醇 为溶剂， 生成 RG 13022
  参考文献：
  名称：

  (Arene)Ru(II) complexes of epidermal growth factor receptor inhibiting tyrphostins with enhanced selectivity and cytotoxicity in cancer cells

  摘要：

  Ru(eta(6)-arene) complexes of epidermal growth factor receptor (EGFR) inhibiting tyrphostins 1a and 1b were prepared, characterized and tested for DNA interaction and bioactivity in four human tumor cell lines. The intrinsic cytotoxicity and cell line selectivity of o-hydroxyanisol la was greatly enhanced in its Ru(eta(6)-p-cymene) complex 2a and in its Ru(eta(6)-toluene) complex 3a. Complex 2a was particularly efficacious against multi-drug resistant EGFR(+) MCF-7/Topo breast carcinoma cells and also against mTOR-dependent EGER( -) HL-60 leukemia cells. Complex 3a showed enhanced activity only against 518A2 melanoma cells and HL-60 cells, which are both known to express the mTOR protein. DNA was strongly metallated (ca. 1.7-2%) by all new Ru complexes without undergoing topological changes. Apparently, by complexation to Ru fragments tyrphostin derivatives can address additional biological targets in a manner instrumental to antitumoral strategies. (C) 2010 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2010.01.040

文献信息

• BCRP/ABCG2 INHIBITOR
  申请人：Yamazaki Ryuta

  公开号：US20090253656A1

  公开（公告）日：2009-10-08

  The present invention is directed to a breast cancer resistance protein (BCRP/ABCG2) inhibitor. The BCRP inhibitor contains, as an active ingredient, an acrylonitrile derivative represented by formula (1): wherein one of R 1 and R 2 represents a cyano group and the other represents a hydrogen atom; Ar 1 represents a group selected from among the groups represented by formulas (2) to (4): and Ar 2 represents an aromatic hydrocarbon group having a condensed ring which may be substituted by a halogen atom, or a group selected from among the groups represented by the following formulas (5) to (15): or a salt thereof.

  该发明涉及一种乳腺癌耐药蛋白（BCRP/ABCG2）抑制剂。该BCRP抑制剂包含以下化合物作为活性成分，其化学式为（1）：其中R1和R2中的一个代表氰基，另一个代表氢原子；Ar1代表从以下化学式（2）至（4）中选出的一种基团：Ar2代表一种含有可能被卤素原子取代的融合环的芳香烃基团，或者从以下化学式（5）至（15）中选出的一种基团：或其盐。
• BCRP/ABCG3 Inhibitor
  申请人：Kabushiki Kaisha Yakult Honsha

  公开号：EP2332905A1

  公开（公告）日：2011-06-15

  A BCRP inhibitor comprising, as an active ingredient, an acrylonitrile derivative represented by formula (1): wherein one of R1 and R2 represents a cyano group and the other represents a hydrogen atom; Ar1 represents a group selected from among the groups represented by formulas (2) to (4): wherein R7 and R8, which are identical to or different from each other, each represent a hydrogen atom, a halogen atom, or a lower alkoxy group; A represents an oxygen atom, a sulfur atom, or NR9; and R9 represents a hydrogen atom or a lower alkyl group; Ar2 represents a group selected from among the groups represented by formulas (5) to (15): wherein R3 represents a hydrogen atom, an oxygen atom (as N-oxide), a lower alkyl group, a lower alkoxy group, a halogen atom, a nitro group, a methylsulfanyl group, a lower hydroxyalkyl group, an aromatic hydrocarbon group which may have a substituent, or NR5 (R6) R5 and R6, which are identical to or different from each other, each represent a hydrogen atom, a lower alkyl group which may have a substituent, a lower hydroxyalkyl group, or an aromatic hydrocarbon group which may have a substituent or heterocyclic group; R5 and R6 may form, with their adjacent nitrogen atom, a heterocyclic ring which may have a substituent; and the hydroxyl group of the lower hydroxyalkyl group or the heterocyclic ring substituted by a hydroxyl group or a lower hydroxyalkyl group may form an ester bond with a phosphoric acid group or a salt thereof or with an acyl group which may have a substituent; R4 represents a hydrogen atom, a lower alkyl group, a phenyl group which may have a substituent, or a benzyl group; X represents a carbon atom, CH, or a nitrogen atom, provided that when A is an oxygen atom, X is not a nitrogen atom; and A, R7, R8, and R9 have the same meanings as defined above; or a salt thereof.

  一种 BCRP 抑制剂，其活性成分包括由式（1）表示的丙烯腈衍生物： 其中 R1 和 R2 中的一个代表氰基，另一个代表氢原子； Ar1 代表选自式（2）至（4）所代表基团中的一个基团： 其中彼此相同或不同的 R7 和 R8 各自代表氢原子、卤素原子或低级烷氧基； A 代表氧原子、硫原子或 NR9；以及 R9 代表氢原子或低级烷基； Ar2 代表选自式 (5) 至 (15) 所代表基团中的一个基团： 其中 R3 代表氢原子、氧原子（作为 N-氧化物）、低级烷基、低级烷氧基、卤素原子、硝基、甲硫 基、低级羟烷基、可具有取代基的芳香烃基或 NR5 (R6) 彼此相同或不同的 R5 和 R6 分别代表一个氢原子、一个可带取代基的低级烷基、一个低级羟烷基或一个可带取代基或杂环基的芳香烃基；R5 和 R6 可与相邻的氮原子形成一个可带取代基的杂环；下羟烷基的羟基或被羟基或下羟烷基取代的杂环可与磷酸基团或其盐或可带有取代基的酰基形成酯键； R4 代表氢原子、低级烷基、可能具有取代基的苯基或苄基； X 代表碳原子、CH 或氮原子，但当 A 是氧原子时，X 不是氮原子；以及 A、R7、R8 和 R9 具有与上述定义相同的含义；或其盐。
• STYRYL-SUBSTITUTED MONOCYCLIC AND BICYCLIC HETEROARYL COMPOUNDS WHICH INHIBIT EGF RECEPTOR TYROSINE KINASE
  申请人：RHONE-POULENC RORER INTERNATIONAL (HOLDINGS) INC.

  公开号：EP0525109A1

  公开（公告）日：1993-02-03
• EP0525109A4
  申请人：——

  公开号：EP0525109A4

  公开（公告）日：1993-06-30
• BCRP/ABCG2 Inhibitor
  申请人：Kabushiki Kaisha Yakult Honsha

  公开号：EP2332905B1

  公开（公告）日：2017-03-01