丙基-104 | 851627-62-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 丙基-104
• 中文别名: 2-[(2-溴乙基)(2,4-二硝基-6-{[2-(膦氧基)乙基]氨基甲酰}苯基)氨基]乙基甲烷磺酸盐
• 英文名称: PR-104
• 英文别名: [3H]-PR-104；2-((2-Bromoethyl)(2,4-dinitro-6-((2-(phosphonooxy)ethyl)carbamoyl)phenyl)amino)ethyl methanesulfonate；2-[N-(2-bromoethyl)-2,4-dinitro-6-(2-phosphonooxyethylcarbamoyl)anilino]ethyl methanesulfonate
• CAS: 851627-62-8
• 化学式: C₁₄H₂₀BrN₄O₁₂PS
• 分子量: 579.276
• InChiKey: GZSOKPMDWVRVMG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  33
• 可旋转键数：
  12
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  243
• 氢给体数：
  3
• 氢受体数：
  13

反应信息

• 作为产物：
  描述：

  2-[(2-bromoethyl)-2-(6-tert-butoxy-8,8-dimethyl-6-oxido-5,7-dioxa-2-aza-6-phosphanon-1-anoyl)-4,6-dinitroanilino]ethyl methanesulfonate 生成 丙基-104
  参考文献：
  名称：

  Nitrophenyl mustard and nitrophenylaziridine alcohols and their corresponding phosphates and their use as targeted cytotoxic agents

  摘要：

  本发明涉及一种新型的硝基苯芥和硝基苯环氧乙烷醇，它们的相应磷酸盐，它们作为靶向细胞毒性药物的使用；作为生物还原药物在低氧肿瘤中的使用，并与硝酸还原酶酶一起用于细胞消融，包括基因定向酶前药治疗（GPEPT）和抗体定向酶前药治疗（ADEPT）。

  公开号：

  US07629332B2

文献信息

• NITROBENZYL DERIVATIVES OF ANTI-CANCER AGENTS
  申请人：OBI PHARMA, INC.

  公开号：US20180086693A1

  公开（公告）日：2018-03-29

  Provided herein are compounds of formula I, wherein the variables are defined herein, processes of making them, and methods of treating cancer comprising administering such compounds.

  本文提供了公式I的化合物，其中变量在此处定义，制备它们的方法，以及包括给予这些化合物的治疗癌症方法。
• [EN] PRODRUG COMPOUNDS ACTIVATED BY AKR1C3 AND THEIR USE FOR TREATING HYPERPROLIFERATIVE DISORDERS<br/>[FR] COMPOSÉS DE TYPE PROMÉDICAMENTS ACTIVÉS PAR AKR1C3 ET LEUR UTILISATION POUR LE TRAITEMENT DE TROUBLES HYPERPROLIFÉRATIFS
  申请人：ACHILLES MEDICAL LTD

  公开号：WO2019190331A1

  公开（公告）日：2019-10-03

  AKR1C3-activated prodrugs of Formula (I), pharmaceutical compositions comprising prodrugs of Formula (I), and their use in the treatment of hyperproliferative diseases such as cancer and for cell ablation. The compounds of the invention are able to penetrate neoplasm tissue and be selectively reduced to an active (cytotoxic) form by contact with an AKR1C3 enzyme found in the neoplasm. This active form is therefore able to ablate AKR1C3-expressing target cells of the neoplasm and therefore has particular utility in the treatment of cancer and other hyperproliferative disorders.

  AKR1C3激活的Formula (I)的前药，包括Formula (I)的前药的药物组合物，以及它们在治疗癌症等高增殖性疾病和细胞消融中的用途。该发明的化合物能够穿透肿瘤组织，并通过与肿瘤中发现的AKR1C3酶接触而选择性地还原为活性（细胞毒性）形式。因此，这种活性形式能够消灭肿瘤中表达AKR1C3的靶细胞，因此在癌症和其他高增殖性疾病的治疗中具有特殊的实用性。
• Nitrophenyl mustard and nitrophenylaziridine alcohols and their corresponding phosphates and their use as targeted cytotoxic agents
  申请人：Auckland Uniservices Limited

  公开号：US07629332B2

  公开（公告）日：2009-12-08

  The present invention relates to a novel nitrophenyl mustard and nitrophenylaziridine alcohols, to their corresponding phosphates, to their use as targeted cytotoxic agents; as bioreductive drugs in hypoxic tumors, and to their use in cell ablation, including gene-directed enzyme-prodrug therapy (GPEPT) and antibody-directed enzymeprodrug therapy (ADEPT), in conjunction with nitroreductase enzymes.

  本发明涉及一种新型的硝基苯芥和硝基苯环氧乙烷醇，它们的相应磷酸盐，它们作为靶向细胞毒性药物的使用；作为生物还原药物在低氧肿瘤中的使用，并与硝酸还原酶酶一起用于细胞消融，包括基因定向酶前药治疗（GPEPT）和抗体定向酶前药治疗（ADEPT）。
• Novel nitrophenyl mustard and nitrophenylaziridine alcohols and their corresponding phosphates and their use as targeted cytotoxic agents
  申请人：Denny William Alexander

  公开号：US20100010094A1

  公开（公告）日：2010-01-14

  The present invention relates to novel nitrophenyl mustard and nitrophenylaziridine alcohols, to their corresponding phosphates, to their use as targeted cytotoxic agents; as bioreductive drugs in hypoxic tumours, and to their use in cell ablation, including gene-directed enzyme-prodrug therapy (GDEPT) and antibody-directed enzyme-prodrug therapy (ADEPT), in conjunction with nitroreductase enzymes.

  本发明涉及新型的硝基苯基芥和硝基苯基环氧丙烷醇，它们对应的磷酸盐，以及它们作为靶向细胞毒性药物的使用；作为缺氧肿瘤中的生物还原药物，并结合硝酸还原酶酶使用于细胞消融，包括基因定向酶前药物治疗（GDEPT）和抗体定向酶前药物治疗（ADEPT）。
• Processes of preparing asymmetric dinitrobenzamide mustard compounds, intermediate compounds useful therein and products obtained therefrom
  申请人：Atwell Graham John

  公开号：US20100121091A1

  公开（公告）日：2010-05-13

  The invention relates to methods of preparing compounds of formula (II) wherein Z represents —OR 1 or N(R 2 )R 2a —, where R 1 is lower alkylene (C 1 -C 6 ), R 2 is lower alkyl or H and R 2a is lower alkylene (C 1 -C 6 ) or H; Q is absent when R 2a is H and is otherwise selected from the group consisting of H, —OH and protected forms of —OH; one of X and Y is halogen and the other is —OSO 2 R 3 , where R 3 is selected from the group consisting of lower alkyl (C 1 -C 6 ), phenyl and CH 2 phenyl. The method comprises the steps of: (a) reacting a compound of formula (I) with aziridineethanol or a 2-[(2-haloethyl)amino]ethanol in the presence of a metal halide, to form a compound of the formula (III) wherein one of X and E is halogen and the other is hydroxy, and (b) reacting the compound of formula (III) with an alkyl- or arylsulfonyl halide or alkyl- or arylsulfonyl anhydride to obtain a compound of the formula (II). The invention also relates to methods of preparing compounds of formula (IV) from the compounds of formula (II) so obtained, and to novel compounds of formula (IIb) useful as intermediates in these methods.

  本发明涉及制备式（II）化合物的方法，其中Z代表—OR1或N（R2）R2a—，其中R1为低碳链（C1-C6），R2为低碳基或H，R2a为低碳链（C1-C6）或H；当R2a为H时，Q不存在，否则Q选择自羟基（—OH）和保护的羟基形式；X和Y中的一个是卤素，另一个是—OSO2R3，其中R3选择自低碳基（C1-C6）、苯基和CH2苯基。该方法包括以下步骤：（a）在金属卤化物的存在下，将式（I）化合物与环氧丙胺乙醇或2-[(2-卤基乙基)氨基]乙醇反应，形成式（III）化合物，其中X和E中的一个是卤素，另一个是羟基，（b）将式（III）化合物与烷基或芳基磺酰卤或烷基或芳基磺酰酐反应，得到式（II）化合物。本发明还涉及从所得到的式（II）化合物制备式（IV）化合物的方法，以及作为这些方法中间体的新型式（IIb）化合物。