{[5-chloro-2,6-dioxo(1,3-dihydropyrimidin-4-yl)]methyl}thiocarboxamidine hydrochloride

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: {[5-chloro-2,6-dioxo(1,3-dihydropyrimidin-4-yl)]methyl}thiocarboxamidine hydrochloride
• 英文别名: 2-(5-chlorouracil-6-ylmethyl)isothiourea hydrochloride；(5-chloro-2,4-dioxo-1H-pyrimidin-6-yl)methyl carbamimidothioate;hydrochloride
• 化学式: C₆H₇ClN₄O₂S*ClH
• 分子量: 271.127
• InChiKey: ARRDUOKHXLVLTB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.27
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  133
• 氢给体数：
  5
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  5-氯-6-(氯甲基)尿嘧啶 在 硫脲 作用下， 以 乙醇 为溶剂， 以81%的产率得到{[5-chloro-2,6-dioxo(1,3-dihydropyrimidin-4-yl)]methyl}thiocarboxamidine hydrochloride
  参考文献：
  名称：

  Cancerous metastasis inhibitors containing uracil derivatives

  摘要：

  这项发明提供了一种药物，具有抑制胸苷磷酸酶活性并抑制癌症转移的作用。具体而言，该发明涉及一种癌症转移抑制剂，其活性成分为以下式（1）所表示的尿嘧啶衍生物：其中R1代表氯、溴或碘原子或氰基或较低烷基基团，R2代表具有氮原子的取代或未取代的4-8元杂环基团或取代或未取代的酰胺硫、胍胺、（较低烷基）酰胺、氨基或类似基团，或其盐。

  公开号：

  US06255314B1

文献信息

• Synthesis and evaluation of 6-methylene-bridged uracil derivatives. Part 2: Optimization of inhibitors of human thymidine phosphorylase and their selectivity with uridine phosphorylase
  作者：Shingo Yano、Hideki Kazuno、Tsutomu Sato、Norihiko Suzuki、Tomohiro Emura、Konstanty Wierzba、Jun-ichi Yamashita、Yukio Tada、Yuji Yamada、Masakazu Fukushima、Tetsuji Asao

  DOI：10.1016/j.bmc.2004.04.046

  日期：2004.7

  A series of novel 6-methylene-bridged uracil derivatives have been optimized for clinical use as the inhibitors of human thymidine phosphorylase (TP). We describe their synthesis and evaluation. Introduction of a guanidino or an amidino group enhanced the in vitro inhibitory activity of TP comparing with formerly reported inhibitor 1. Their selectivity for TP based on uridine phosphorylase inhibitory

  已经优化了一系列新颖的6-亚甲基桥接的尿嘧啶衍生物，以作为人胸苷磷酸化酶（TP）的抑制剂用于临床。我们描述它们的综合和评估。与以前报道的抑制剂1相比，胍基或a基的引入增强了TP的体外抑制活性。还评估了它们基于尿苷磷酸化酶抑制活性对TP的选择性。化合物2（TPI）由于其强大的TP抑制作用和2'-脱氧-5-（三氟甲基）尿苷（F（3）dThd）药代动力学的出色调节作用，已被选择用于临床评估。结果，TAS-102（F（3）dThd和TPI的组合）目前处于1期临床研究中。
• Uracil derivatives, and antitumor effect potentiator and antitumor agent
  申请人：Taiho Pharmaceutical Co., Ltd.

  公开号：US05744475A1

  公开（公告）日：1998-04-28

  The invention relates to novel uracil derivatives having excellent inhibiting effects of human derived thymidine phosphorylase and anti-tumor activity. The pharmaceutical compositions, anti-tumor potentiators, antitumor agents containing such novel compounds, and a process for their preparation and use is described. The novel compounds satisfy the general formula (1): ##STR1##

  该发明涉及具有出色的抑制人源胸腺嘧啶核苷磷酸化酶和抗肿瘤活性的新型尿嘧啶衍生物。描述了含有这种新型化合物的药物组合物、抗肿瘤增效剂、抗肿瘤药物以及它们的制备和使用方法。这些新型化合物符合一般式（1）。
• Uracil derivatives and antitumor effect potentiator and antitumor agent containing the same
  申请人：Taiho Pharmaceutical Co., Ltd.

  公开号：US06294535B1

  公开（公告）日：2001-09-25

  The invention relates to novel uracil derivatives having excellent inhibiting effects on human derived thymidine phosphorylates and anti-tumor activity. The pharmaceutical compositions, anti-tumor potentiators and antitumor agents containing such novel compounds, and a process for their preparation and use are described. The novel uracil derivative compounds are represented by the general formula (1′):

  本发明涉及新型尿嘧啶衍生物，具有出色的抑制人源胸腺嘧啶激酶和抗肿瘤活性。描述了含有这种新化合物的药物组合物、抗肿瘤增效剂和抗肿瘤剂，以及它们的制备和使用方法。这些新型尿嘧啶衍生物化合物由通式（1'）表示：
• URACIL DERIVATIVES, AND ANTITUMOR EFFECT POTENTIATOR AND ANTITUMOR AGENT CONTAINING THE SAME
  申请人：TAIHO PHARMACEUTICAL COMPANY LIMITED

  公开号：EP0763529A1

  公开（公告）日：1997-03-19

  Provided are a uracil derivative represented by the following formula (1): wherein R1 represents a chlorine, bromine or iodine atom or a cyano or lower alkyl group; and R2 represents a 4-8 membered heterocyclic group having 1-3 nitrogen atoms, which may be substituted by one or more lower alkyl, imino, hydroxyl, hydroxymethyl, methanesulfonyloxy, amino or nitro groups; an amidinothio group, one or more of the hydrogen atom(s) on one or both of the nitrogen atoms of which may each be substituted by a lower alkyl group; a guanidino group, one or more of the hydrogen atom(s) on one, two or all of the nitrogen atoms of which may each be substituted by a lower alkyl or cyano group; a (lower alkyl)amidino group; an amino group, one or both of the hydrogen atoms on the nitrogen atom of which may each be substituted by a lower alkyl group; a group -CH2N(Ra)Rb in which Ra and Rb may be the same or different and each represents a hydrogen atom or a lower alkyl group or Ra and Rb may form a pyrrolidine ring together with the nitrogen atom to which Ra and Rb are bonded; a group -NH-(CH2)m-Z in which Z represents an amino group, one or both of the hydrogen atoms on the nitrogen atom of which may each be substituted by a lower alkyl group, or a cyano group, and m stands for an integer of from 0 to 3; a group NRc(CH2)n-OH in which Rc represents a hydrogen atom or a lower alkyl group, and n stands for a natural number of from 1 to 4; a group -X-Y in which X represents S or NH, and Y represents a 2-imidazolin-2-yl, 2-imidazolyl, 1-methylimidazol-2-yl, 1,2,4-triazol-3-yl, 2-pyrimidyl or 2-benzimidazolyl group which may be substituted by one or more lower alkyl groups; or a ureido or thioureido group, one or more of the hydrogen atom(s) on one or both of the nitrogen atoms of which may each be substituted by a lower alkyl group; or a salt thereof; as well as a pharmaceutical, antitumor effect potentiator and antitumor agent containing same as an active ingredient.

  本发明提供了由下式(1)代表的尿嘧啶衍生物： 其中 R1 代表氯、溴或碘原子或氰基或低级烷基；R2 代表具有 1-3 个氮原子的 4-8 位杂环基团，可被一个或多个低级烷基、亚氨基、羟基、羟甲基、甲磺酰氧基、氨基或硝基取代；脒基，其一个或多个氮原子或两个氮原子上的一个或多个氢原子可分别被低级烷基取代；胍基，其中一个、两个或全部氮原子上的一个或多个氢原子可分别被低级烷基或氰基取代； （低级烷基）脒基； 氨基，其中一个或两个氮原子上的氢原子可分别被低级烷基取代；基团-CH2N(Ra)Rb，其中 Ra 和 Rb 可以相同或不同，各自代表一个氢原子或一个低级烷基，或 Ra 和 Rb 可与 Ra 和 Rb 键合的氮原子一起形成一个吡咯烷环；基团-NH-(CH2)m-Z，其中 Z 代表氨基，其氮原子上的一个或两个氢原子可分别被低级烷基或氰基取代，m 代表 0 至 3 的整数； 基团 NRc(CH2)n-OH，其中 Rc 代表氢原子或低级烷基，n 代表 1 至 4 的自然数；基团-X-Y，其中 X 代表 S 或 NH，Y 代表可被一个或多个低级烷基取代的 2-咪唑啉-2-基、2-咪唑基、1-甲基咪唑-2-基、1,2,4-三唑-3-基、2-嘧啶基或 2-苯并咪唑基；或脲基或硫脲基，其中一个或多个氮原子上的氢原子或两个氮原子上的氢原子可分别被一个低级烷基取代；或其盐；以及含有上述物质作为活性成分的药物、抗肿瘤增效剂和抗肿瘤剂。
• CANCEROUS METASTASIS INHIBITORS CONTAINING URACIL DERIVATIVES
  申请人：TAIHO PHARMACEUTICAL COMPANY LIMITED

  公开号：EP0884051A1

  公开（公告）日：1998-12-16

  This invention provides a drug which has inhibitory activities against thymidine phosphorylase and inhibits metastasis of a cancer. Specifically, this invention relates to a cancerous metastasis inhibitor comprising, as an active ingredient, a uracil derivative represented by the following formula (1): wherein R1 represents a chlorine, bromine or iodine atom or a cyano or lower alkyl group and R2 represents a substituted or unsubstituted 4-8 membered heterocyclic group having nitrogen atoms or a substituted or unsubstituted amidinothio, guanidino, (lower alkyl)amidino, amino or like group, or a salt thereof.

  本发明提供了一种对胸苷磷酸化酶具有抑制活性并能抑制癌症转移的药物。具体地说，本发明涉及一种癌症转移抑制剂，其活性成分包括下式（1）所代表的尿嘧啶衍生物： 其中 R1 代表氯、溴或碘原子或氰基或低级烷基，R2 代表取代或未取代的具有氮原子的 4-8 位杂环基团或取代或未取代的脒基、胍基、（低级烷基）脒基、氨基或类似基团，或其盐。