AG 83 | 118409-64-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: AG 83
• 英文别名: (3,5-dihydroxybenzylidene)malononitrile；1,1-dicyano-2-(3,5-dihydroxyphenyl)ethylene；2-[(3,5-Dihydroxyphenyl)methylidene]propanedinitrile
• CAS: 118409-64-6
• 化学式: C₁₀H₆N₂O₂
• 分子量: 186.17
• InChiKey: CEQLJWDOOOWWJE-UHFFFAOYSA-N

物化性质

• 熔点：
  260 °C
• 沸点：
  445.6±30.0 °C(Predicted)
• 密度：
  1.428±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  88
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-(3,5-dimethoxybenzylidene)malononitrile 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 以29%的产率得到AG 83
  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

• Polyhydroxylated Phenylacrylic Acid Derivatives as New Anti-tumor Agents
  作者：Sajjat Hussoin、George B. FitzGerald、Michael M. Wick

  DOI：10.1002/jps.2600800503

  日期：1991.5

  Preliminary evidence indicates that antitumor agents containing the o-dihydroxybenzene moiety exhibit enhanced antitumor activity toward malignant cells of high oxidative potential, such as melanoma cells. Based on this consideration, 11 hydroxybenzene acrylic acid derivatives of differing redox potential were prepared as potential substrates for the melanoma specific enzyme tyrosinase, that might

  初步证据表明，含有邻二羟基苯部分的抗肿瘤药对黑色素瘤细胞等具有高氧化潜能的恶性细胞表现出增强的抗肿瘤活性。基于此考虑，制备了具有不同氧化还原电势的11种羟苯丙烯酸衍生物作为黑素瘤特异性酶酪氨酸酶的潜在底物，其可能表现出一般的抗肿瘤活性并增强了对黑素瘤细胞的细胞毒性。这些化合物中的五个[α-氰基-β-（4-羟基苯基）-，α-氰基-β-（3,4-二羟基苯基）-和α-氰基-β-（3,4,5-三羟基苯基）丙烯酸发现酪氨酸酶（THPPA）和3,4-二羟基-和3,4,5-三羟基苯并氰基乙酰胺]是酪氨酸酶的底物，Km值为0.08至4.13 mM，Vmax值为0.18至3.02。这些数据表明，随着羟基数目的增加，氧化速率增加，并且氰酰胺比相应的氰酸的反应更快，其中二氰化物的反应性最低。相反，氰酰胺作为底物的效果不如氰酸。体外研究表明，除两种化合物外，所有化合物均对L1210（IC50范围为21-980 m
• Benzylidene-malononitrile derivatives for the inhibition of proliferative processes in mammalian cells
  申请人：YISSUM RESEARCH DEVELOPMENT COMPANY OF THE HEBREW UNIVERSITY OF JERUSALEM

  公开号：EP0322738A2

  公开（公告）日：1989-07-05

  There are provided pharmaceutical compositions containing as an active ingredient a compound of the general formula (I): wherein R₁ and R₂ are each independently CN, CONH₂ or COOH or one of R₁ and R₂ may be -CSNH₂ or, when R₁ is CN, R₂ can also be the group R₃ is H, CH₃ or OH, R₄, R₅, R₆, R₇ are each independently H, OH, C₁₋₅ alkyl, C₁₋₅ alkoxy. NH₂, CHO, halogen, NO₂ or COOH, or R₄ and R₅ together may represent a group -O-CH₂-O-; provided that: (a) when R₄ and R₇ are each OH, R₃, R₅ and R₆ are each H and one of R₁ and R₂ is CN, then the other of R₁ and R₂ cannot be CONH₂; and (b) when R₃ and R₇ are each H, R₅ is OH and R₄ and R₆ are both H or both C₁₋₅ alkyl, then R₁ is CN and R₂ is CN or the group or a pharmaceutically acceptable salt thereof. There are also provided some novel compounds of formula (I) above. The compositions and compounds according to the invention are efficient protein-tyrosine kinase inhibitors and are suitable for the inhibition of proliferative processes in mammalian cells.

  提供了含有通式(I)化合物作为活性成分的药物组合物： 其中 R₁ 和 R₂ 各自独立地为 CN、CONH₂ 或 COOH，或者 R₁ 和 R₂ 中的一个可以是 -CSNH₂，或者当 R₁ 是 CN 时，R₂ 也可以是基团 R₃ 是 H、CH₃ 或 OH、 R₄、R₅、R₆、R₇各自独立地为 H、OH、C₁₋₅烷基、C₁₋₅烷氧基。NH₂、CHO、卤素、NO₂或 COOH，或 R₄ 和 R₅ 可共同代表一个基团 -O-CH₂-O-； 条件是(a) 当 R₄ 和 R₇ 均为 OH，R₃、R₅ 和 R₆ 均为 H，且 R₁ 和 R₂ 中的一个为 CN 时，则 R₁ 和 R₂ 中的另一个不能为 CONH₂；(b) 当 R₃ 和 R₇ 分别为 H、R₅ 为 OH 且 R₄ 和 R₆ 均为 H 或均为 C₁₋₅ 烷基时，则 R₁ 为 CN，R₂ 为 CN 或基团 或其药学上可接受的盐。 还提供了一些上述式 (I) 的新型化合物。 根据本发明的组合物和化合物是高效的蛋白酪氨酸激酶抑制剂，适用于抑制哺乳动物细胞的增殖过程。
• Cosmestic composition
  申请人：UNILEVER PLC

  公开号：EP0572167A1

  公开（公告）日：1993-12-01

  A composition suitable for topical application to mammalian skin and hair for inducing, maintaining or increasing hair growth comprises a hair growth promoter chosen from glutamic acid derivatives and salts thereof. The composition preferably also comprises an activity enhancer which may be chosen from hair growth stimulants, penetration enhancers and cationic polymers.

  一种适用于哺乳动物皮肤和毛发的外用组合物，可诱导、维持或增加毛发生长，其中包括一种毛发生长促进剂，选自谷氨酸衍生物及其盐类。该组合物最好还包含一种活性增强剂，它可以选自毛发生长刺激剂、渗透增强剂和阳离子聚合物。
• Cosmetic composition containing DOPA derivatives
  申请人：UNILEVER PLC

  公开号：EP0580409A2

  公开（公告）日：1994-01-26

  A composition for topical application to human hair or skin contains a chemical analogue of dihydroxyphenyl alanine (DOPA). This chemical analogue can be absorbed by skin or by a hair follicle and metabolised in-vivo, thus leading to the formation of melanin in skin or to the growth of melanin-pigmented hair. Consequently the composition can give controlled skin darkening to mimic sun-induced tanning or can bring about the growth of dar hair in place of the grey or white hair.

  一种用于人体毛发或皮肤局部涂抹的组合物含有一种二羟基苯丙氨酸（DOPA）的化学类似物。这种化学类似物可被皮肤或毛囊吸收并在体内代谢，从而导致皮肤黑色素的形成或黑色素毛发的生长。因此，这种成分可以控制皮肤变黑，模拟日光引起的晒黑，或使灰发或白发长出黑发。
• Cosmetic composition containing hair-growth promoter
  申请人：UNILEVER PLC

  公开号：EP0571198A1

  公开（公告）日：1993-11-24

  A composition suitable for topical application to mammalian skin and hair for inducing, maintaining or increasing hair growth comprises a hair growth promoter chosen from glutamine derivatives and salts thereof. The composition preferably also comprises an activity enhancer which may be chosen from hair growth stimulants, penetration enhancers and cationic polymers.

  一种适用于哺乳动物皮肤和毛发的外用组合物，可诱导、维持或增加毛发生长，其中包括一种毛发生长促进剂，选自谷氨酰胺衍生物及其盐类。该组合物最好还包含一种活性增强剂，它可以选自毛发生长刺激剂、渗透增强剂和阳离子聚合物。