{4-[(E)-3-(3,4-Dichloro-phenyl)-3-oxo-propenyl]-phenoxy}-acetic acid | 31824-95-0

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: {4-[(E)-3-(3,4-Dichloro-phenyl)-3-oxo-propenyl]-phenoxy}-acetic acid
• 英文别名: 2-[4-[3-(3,4-Dichlorophenyl)-3-oxoprop-1-enyl]phenoxy]acetic acid
• CAS: 31824-95-0
• 化学式: C₁₇H₁₂Cl₂O₄
• 分子量: 351.186
• InChiKey: HYBWERCTQJOGFB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2918990090

反应信息

• 作为反应物：
  描述：

  {4-[(E)-3-(3,4-Dichloro-phenyl)-3-oxo-propenyl]-phenoxy}-acetic acid 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二甲基亚砜 、 乙腈 为溶剂， 反应 72.0h， 生成
  参考文献：
  名称：

  Monochalcoplatin：一种主动转运，可快速还原且高度有效的PtIV抗癌前药

  摘要：

  最近，作为下一代铂基抗肿瘤药的候选药物，Pt IV前药引起了广泛的关注。在这里我们报告发现和评估monochalcoplatin，一种单羧基化的Pt IV前药，是迄今为止最具细胞毒性的Pt IV前药之一。与它的二羧基化对应物查尔铂相比，单查铂在癌细胞中有效且迅速地积累，这并不归因于其亲脂性。前药迅速减少，引起DNA损伤，并诱导细胞凋亡，从而在顺铂敏感和耐药细胞中均具有优异的细胞毒性，IC 50值在纳摩尔范围内。这些IC 50该值比顺铂高422倍。一项详细的机理研究表明，monochalcoplatin通过转运蛋白介导的过程主动进入细胞。此外，单氯铂在体内结直肠肿瘤模型中显示出显着的抗肿瘤活性。我们的研究表明一种可行的策略，用于设计更有效的Pt IV前药，以通过调节细胞摄取途径和激活过程来克服耐药性。

  DOI：

  10.1002/anie.201804314
• 作为产物：
  描述：

  3,4-二氯苯乙酮 、 4-甲酰苯氧基乙酸 在 potassium hydroxide 作用下， 以 甲醇 为溶剂， 反应 12.0h， 以80%的产率得到{4-[(E)-3-(3,4-Dichloro-phenyl)-3-oxo-propenyl]-phenoxy}-acetic acid
  参考文献：
  名称：

  Chalcoplatin, a dual-targeting and p53 activator-containing anticancer platinum(iv) prodrug with unique mode of action

  摘要：

  一举两得：一种p53激活剂与顺铂结合成为单一的抗癌药物，使细胞毒性协同改善。

  DOI：

  10.1039/c4cc10409a

文献信息

• Derivatives of phenoxy acetic acid and phenoxymethyltetrazole having antitumor activity
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0947494A1

  公开（公告）日：1999-10-06

  The present intention relates to the use derivatives of phenoxy acetic acid and of phenoxymethyl tetrazole of formula (I) wherein: the -O-C(R1)(R2)-(CH2)p-A group can be in ortho, meta or para position; A is selected from -COOH, -COO-(C1-C4)alkyl, -CN or a group of formula in which R' is hydrogen or (C1-C4)alkyl; or the group A-(CH2)p-C(R1)(R2)- is selected from phenyl, benzyl or (indolyl)methyl, which may be subsituted by R4 groups; p is 0, 1 or 2; R1 and R2 are independently selected from hydrogen or (C1-C8)alkyl or they form, together with the carbon atom to which they are linked, a (C3-C7)cycloalkyl group; R4 are from 0 to 2 substituents independently selected from chlorine, bromine, iodine, fluorine, linear or branched (C1-C8)alkyl, hydroxy, (C1-C4)alkoxy, (C1-C4)acyl groups; or the group in formula (I) is a naphtyl group which may be on its turn substituted by R4 groups; n is an integer from 1 to 4; m is 0 or 1; B is selected from linear or branched C1-C10 alkyl, -CO-C(R3)=CH-R, -CH=C(R3)-CO-Ar, -CO-CH(R3)-CH2-R or CO-CH(R3)-CH2-NR5R6 when m is 0 or is -CH=C(R3)-CO-Ar when m is 1; R is selected from hydrogen, -Ar or -CO-Ar; R3 is hydrogen or a (C1-C8)alkyl group; R5 and R6 are independently a (C1-C4)alkyl group or they form, together with the nitrogen atom to which they are linked, a piperidino, piperazino, (C1-C8)alkylpiperazino, morpholino or thiomorpholino group; Ar is a phenyl group which can be unsubstituted or substituted with from 1 to 3 groups independently selected from chlorine, bromine, iodine, fluorine, linear or branched (C1-C8)alkyl, hydroxy, (C1-C4)alkoxy, (C1-C4)acyl groups, stereoisomers thereof or salts thereof with pharmaceuticaly acceptable acids or basis, for the preparation of a medicament having MDM2 antagonistic activity, new compounds of the above formula, and pharmaceutical compositions containing at least one of those compounds.

  本发明涉及苯氧乙酸和苯氧甲基四唑的衍生物的使用，其化学式为（I）：其中：-O-C（R1）（R2）-（CH2）p-A基团可以处于邻位、间位或对位；A从-COOH，-COO-（C1-C4）烷基，-CN或式中R'为氢或（C1-C4）烷基的基团中选择；或式中A-（CH2）p-C（R1）（R2）-的基团从苯基，苄基或（吲哚基）甲基中选择，可以被R4基取代；p为0、1或2；R1和R2独立选择自氢或（C1-C8）烷基，或与它们链接的碳原子一起形成（C3-C7）环烷基；R4是从0到2个取代基，可独立选择自氯、溴、碘、氟、线性或支链（C1-C8）烷基、羟基、（C1-C4）烷氧基、（C1-C4）酰基基团；或式（I）中的基团是一个萘基，可以被R4基取代；n是1到4的整数；m为0或1；B从线性或支链C1-C10烷基，-CO-C（R3）=CH-R，-CH=C（R3）-CO-Ar，-CO-CH（R3）-CH2-R或CO-CH（R3）-CH2-NR5R6中选择，当m为0时，或者当m为1时，为-CH=C（R3）-CO-Ar；R从氢、-Ar或-CO-Ar中选择；R3为氢或（C1-C8）烷基；R5和R6独立选择自（C1-C4）烷基或与它们链接的氮原子一起形成哌啶基，哌嗪基，（C1-C8）烷基哌嗪基，吗啉基或硫代吗啉基；Ar是苯基，可以是未取代或取代的，取代基独立选择自氯、溴、碘、氟、线性或支链（C1-C8）烷基、羟基、（C1-C4）烷氧基、（C1-C4）酰基基团，其立体异构体或与药用可接受的酸或碱盐形成的盐，用于制备具有MDM2拮抗活性的药物，上述化合物的新化合物以及含有至少其中一种化合物的制药组合物。
• CYTOTOXIC PLATINUM COMPLEX, ITS PREPARATION AND THERAPEUTIC USE
  申请人：City University of Hong Kong

  公开号：US20180155382A1

  公开（公告）日：2018-06-07

  Platinum(IV) complexes especially suitable for antitumor therapy and methods for their preparation. Further provided is a method for treating a subject, in particular a human, suffering from a disease comprising administering a platinum(IV) complex of the present invention, which disease is especially preferably but not exclusively a cancer. Further provided is a method of inhibiting the growth of tumor cells by contacting the cells with a platinum(IV) complex of the present invention and a pharmaceutical composition comprising a platinum(IV) complex of the present invention. The platinum(IV) complexes of the present invention represent a novel class of platinum anticancer prodrugs for the treatment of diseases especially of cancer. The platinum(IV) complexes of the present invention exhibit advantageously high cytotoxic activity in various cancer types superior to commonly used platinum-based complexes. In addition, the complexes proved to be highly effective even against cisplatin-resistant cancers.

  本发明提供了特别适用于抗肿瘤治疗的铂(IV)配合物及其制备方法。此外，本发明还提供了一种治疗患有疾病，特别是癌症的受试者，尤其是人类的方法，包括给予本发明的铂(IV)配合物。本发明还提供了一种通过接触本发明的铂(IV)配合物来抑制肿瘤细胞生长的方法，以及包含本发明的铂(IV)配合物的药物组合物。本发明的铂(IV)配合物代表了一种新型的铂类抗癌前药，用于治疗特别是癌症等疾病。本发明的铂(IV)配合物在各种癌症类型中表现出优越的细胞毒性活性，优于常用的铂类配合物。此外，这些配合物在对顶铂耐药性癌症中也表现出高度的有效性。
• Chalcoplatin, a dual-targeting and p53 activator-containing anticancer platinum(<scp>iv</scp>) prodrug with unique mode of action
  作者：Lili Ma、Rong Ma、Yiping Wang、Xiaoyue Zhu、Junliang Zhang、Hoi Ching Chan、Xianfeng Chen、Wenjun Zhang、Sung-Kay Chiu、Guangyu Zhu

  DOI：10.1039/c4cc10409a

  日期：——

  Killing two birds with one stone: a p53 activator was conjugated with cisplatin as a single anticancer agent, leading to synergistically improved cytotoxicity.

  一举两得：一种p53激活剂与顺铂结合成为单一的抗癌药物，使细胞毒性协同改善。
• Derivatives of phenoxy acetic acid and of phenoxymethyl tetrazole having antitumor activity
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0947511A1

  公开（公告）日：1999-10-06

  The present invention relates to the use derivatives of phenoxy acetic acid and of phenoxymethyl tetrazole of formula (I) wherein A, B, R1, R2, R4, p, n and m have the above-stated meanings, their pharmaceutically acceptable acids or basis to produce pharmaceutical agents for the treatment of diseases where MDM2 antagonistic activity is involved, processes for their production and pharmaceutical agents which contain these compounds having MDM2antagonistic activity.

  本发明涉及使用式（I）的苯氧乙酸和苯氧甲基四唑的衍生物 其中 A、B、R1、R2、R4、p、n 和 m 具有上述含义，它们的药学上可接受的酸或碱用于生产治疗涉及 MDM2 拮抗活性的疾病的药剂，它们的生产工艺以及含有这些具有 MDM2 拮抗活性的化合物的药剂。
• Monochalcoplatin: An Actively Transported, Quickly Reducible, and Highly Potent Pt^IV Anticancer Prodrug
  作者：Lili Ma、Na Wang、Rong Ma、Cai Li、Zoufeng Xu、Man-Kit Tse、Guangyu Zhu

  DOI：10.1002/anie.201804314

  日期：2018.7.16

  Recently, PtIV prodrugs have attracted much attention as the next generation of platinum‐based antineoplastic drug candidates. Here we report the discovery and evaluation of monochalcoplatin, a monocarboxylated PtIV prodrug that is among the most cytotoxic PtIV prodrugs to date. Compared with its dicarboxylated counterpart chalcoplatin, monochalcoplatin accumulates astonishingly effectively and rapidly

  最近，作为下一代铂基抗肿瘤药的候选药物，Pt IV前药引起了广泛的关注。在这里我们报告发现和评估monochalcoplatin，一种单羧基化的Pt IV前药，是迄今为止最具细胞毒性的Pt IV前药之一。与它的二羧基化对应物查尔铂相比，单查铂在癌细胞中有效且迅速地积累，这并不归因于其亲脂性。前药迅速减少，引起DNA损伤，并诱导细胞凋亡，从而在顺铂敏感和耐药细胞中均具有优异的细胞毒性，IC 50值在纳摩尔范围内。这些IC 50该值比顺铂高422倍。一项详细的机理研究表明，monochalcoplatin通过转运蛋白介导的过程主动进入细胞。此外，单氯铂在体内结直肠肿瘤模型中显示出显着的抗肿瘤活性。我们的研究表明一种可行的策略，用于设计更有效的Pt IV前药，以通过调节细胞摄取途径和激活过程来克服耐药性。