5-cyclopropyl-2-thioxo-2,3-dihydropyrimidin-4(1H)-one | 59698-21-4

• 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-cyclopropyl-2-thioxo-2,3-dihydropyrimidin-4(1H)-one
• 英文别名: 5-Cyclopropyl-2-thioxo-2,3-dihydro-1H-pyrimidin-4-one；5-cyclopropyl-2-sulfanylidene-1H-pyrimidin-4-one
• CAS: 59698-21-4
• 化学式: C₇H₈N₂OS
• mdl: MFCD10688279
• 分子量: 168.219
• InChiKey: QDZCJOQOJDJXCQ-UHFFFAOYSA-N

物化性质

• 熔点：
  211-212 °C
• 密度：
  1.41±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.428
• 拓扑面积：
  73.2
• 氢给体数：
  2
• 氢受体数：
  2

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2933599090

反应信息

• 作为反应物：
  描述：

  5-cyclopropyl-2-thioxo-2,3-dihydropyrimidin-4(1H)-one 在 盐酸 、 N,N-二异丙基乙胺 、 三氯氧磷 作用下， 以 1,4-二氧六环 、 水 、 异丙醇 、 乙腈 为溶剂， 反应 1.0h， 生成 N4-(3-amino-propyl)-5-cyclopropyl-N2-(3-fluoro-phenyl)-pyrimidine-2,4-diamine hydrochloride
  参考文献：
  名称：

  [EN] PYRIMIDINE DERIVATIVES CAPABLE OF INHIBITING ONE OR MORE KINASES
  [FR] DÉRIVÉS DE PYRIMIDINE CAPABLES D'INHIBER UNE OU PLUSIEURS KINASES

  摘要：

  本发明的第一个方面涉及式(I)的化合物，或其药学上可接受的盐或酯，式(I)如下：其中：R1为C3-8环烷基；X为O、NR7或C3-6杂环烷基；R2为芳基、杂芳基、融合或未融合的芳基-C3-6杂环烷基或融合或未融合的杂芳基-C3-6杂环烷基，每个基可选择地由来自芳基、杂芳基、C1-6烷基、C3-7环烷基和A基的一个或多个取代基取代，其中所述C1-6烷基基可选择地由来自芳基、杂芳基、R10和A基的一个或多个取代基取代，所述杂芳基可选择地由一个或多个R10基取代；以及所述C3-6杂环烷基基可选择地包含一个或多个来自氧、硫、氮和CO的基；R3为C1-6烷基，可选择地由一个或多个来自芳基、杂芳基、-NR4R5、-OR6、-NR7(CO)R6、-NR7(CO)NR4R5、-NR7SO2R6、-NR7COOR7、-CONR4R5、C3-6杂环烷基和式(a, b, c)的取代基取代；其中R4-7和A如权利要求中所定义。进一步方面涉及所述化合物在治疗各种治疗性疾病中的使用，特别是作为一个或多个激酶的抑制剂。

  公开号：

  WO2009122180A1
• 作为产物：
  描述：

  环丙乙酸 在 吡啶 、 正丁基锂 、 草酰氯 、 N-环己基异丙基胺 、 N,N-二甲基甲酰胺 作用下， 以 苯 为溶剂， 反应 4.0h， 生成 5-cyclopropyl-2-thioxo-2,3-dihydropyrimidin-4(1H)-one
  参考文献：
  名称：

  Free Radical Rearrangements in Uracil Derivatives

  摘要：

  As part of an effort to develop general probes for radical reactions involving DNA bases, several uracil derivatives were synthesized. The rates of the cyclopropyl carbinyl rearrangement in these systems were evaluated by means of competition experiments. The results indicate that when a cyclopropyl group is substituted in the 5-position of uracil, the rearrangement occurs very slowly-with a rate constant of <2.5 x 10(4) s(-1). On the other hand, the analog of the 5-hexenyl radical cyclization onto the 5,6-double bond of uracil derivatives occurs with rates which were similar to the parent process: (4.0-8.9) x 10(4) s(-1). The experimental results along with semiempirical calculations show that radicals 23 and 25 are unusually stable species. These results explain why no rearrangements are observed when a cyclopropyl-substituted thymine dimer is cleaved by reductive single electron transfer.

  DOI：

  10.1021/jo00096a021

文献信息

• 作为Hedgehog信号传导的嘧啶胺类和吡啶胺 类抑制剂
  申请人：江苏先声药业有限公司

  公开号：CN103864770B

  公开（公告）日：2019-06-11

  本发明涉及作为Hedgehog信号传导的嘧啶胺类和吡啶胺类抑制剂，其为具式（I）结构的化合物或其药学上可接受的盐，本发明还涉及这些化合物可以作为hedgehog信号传导抑制剂的医药用途。
• Discovery of novel 4-(2-pyrimidinylamino)benzamide derivatives as highly potent and orally available hedgehog signaling pathway inhibitors
  作者：Minhang Xin、Liandi Zhang、Qiu Jin、Feng Tang、Jun Wen、Liyun Gu、Lingfei Cheng、Yong Zhao

  DOI：10.1016/j.ejmech.2016.01.018

  日期：2016.3

  A series of novel hedgehog signaling pathway inhibitors have been designed by structural modification based on the former reported scaffold of 4-(2-pyrimidinylamino)benzamide. The SAR for this series was described and many derivatives showed potent inhibitory activity. Among these compounds, compounds 12af and 12bf were identified to have high potency and optimal PK profiles. Although both of compounds

  基于以前报道的4-（2-嘧啶基氨基）苯甲酰胺的支架，通过结构修饰设计了一系列新颖的刺猬信号途径抑制剂。描述了该系列的SAR，许多衍生物显示出有效的抑制活性。在这些化合物中，化合物12af和12bf被确定具有高效力和最佳PK分布。尽管化合物12af和12bf在LS-174T裸鼠模型中均未显示出强大的抗肿瘤功效，但由于它们对Hh信号通路的强大效力和出色的PK特性，它们有望成为Hh信号抑制剂的候选者，值得在其他Hh信号手术中进一步评估肿瘤模型。
• Synthesis and antiviral activity of deoxy analogs of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) as potent and selective anti-HIV-1 agents
  作者：Hiromichi Tanaka、Hideaki Takashima、Masaru Ubasawa、Kouichi Sekiya、Issei Nitta、Masanori Baba、Shiro Shigeta、Richard T. Walker、Erik De Clercq、Tadashi Miyasaka

  DOI：10.1021/jm00103a009

  日期：1992.12

  substitution in the acyclic structure of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)-thymine (HEPT) on anti-HIV-1 activity was investigated by synthesizing a series of deoxy analogs and related compounds. Preparation of 1-[(2-alkyloxyethoxy)methyl]-6- (phenylthio)thymine (2-4) derivatives was carried out based on alkylation of HEPT with primary alkyl halides. Preparation of the 1-[(alkyloxy)methyl]-6-(phenylthio)thymine

  通过合成一系列脱氧类似物和相关化合物，研究了1-[（（2-羟基乙氧基）甲基] -6-（苯硫基）-胸腺嘧啶（HEPT）的无环结构中的取代对抗HIV-1活性的影响。基于HEPT与伯烷基卤化物的烷基化，进行1-[（（2-烷氧基乙氧基）甲基] -6-（苯硫基）胸腺嘧啶（2-4）衍生物的制备。进行了1-[（（烷氧基）甲基] -6-（苯硫基）胸腺嘧啶（26-31）和1-[（（烷氧基）甲基] -6-（芳硫基）-2-硫尿嘧啶（32-45）衍生物的制备根据LDA对1-[（（烷氧基）-甲基]胸腺嘧啶（9-14）和1-[（（烷氧基）甲基] -2-硫氧嘧啶（15-25）进行锂化反应，然后与二芳基二硫化物反应。2-硫尿嘧啶衍生物的氧化水解得到1-[（（烷氧基）甲基] -6-（芳硫基）尿嘧啶衍生物（46-57）。1-烷基-6-（苯硫基）胸腺嘧啶（59-61）衍生物是基于6-（苯硫基）胸腺嘧啶（58）的烷基化制备的。H
• Compound
  申请人：Mciver Edward Giles

  公开号：US20100056524A1

  公开（公告）日：2010-03-04

  A first aspect of the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt or ester thereof, wherein: R 1 is C 3-8 -cycloalkyl; X is O, NR 7 or C 3-6 -heterocycloalkyl; R 2 is aryl, heteroaryl, fused or unfused aryl-C 3-6 -heterocycloalkyl or fused or unfused heteroaryl-C 3-6 -heterocycloalkyl, each of which is optionally substituted by one or more substitutents selected from aryl, heteroaryl, C 1-6 -alkyl, C 3-7 -cycloalkyl and a group A, wherein said C 1-6 -alkyl group is optionally substituted by one or more substituents selected from aryl, heteroaryl, R 10 and a group A, said heteroaryl group is optionally substituted by one or more R 10 groups; and wherein said C 3-6 -heterocycloalkyl group optionally contains one or more groups selected from oxygen, sulfur, nitrogen and CO; R 3 is C 1-6 -alkyl optionally substituted by one or more substituents selected from aryl, heteroaryl, —NR 4 R 5 , —OR 6 , —NR 7 (CO)R 6 , —NR 7 (CO)NR 4 R 5 , —NR 7 SO 2 R 6 , —NR 7 COOR 7 , —CONR 4 R 5 , C 3-6 -heterocycloalkyl and wherein R 4-7 and A are as defined in the claims. Further aspects relate to the use of said compounds in the treatment of various therapeutic disorders, and more particularly as inhibitors of one or more kinases.

  本发明的第一方面涉及化合物(I)的公式，或其药学上可接受的盐或酯，其中： R1是C3-8环烷基；X是O，NR7或C3-6杂环烷基；R2是芳基、杂芳基、融合或未融合的芳基-C3-6杂环烷基或融合或未融合的杂芳基-C3-6杂环烷基，其中每个基团可选地由一个或多个取代基选自芳基、杂芳基、C1-6烷基、C3-7环烷基和A组成，其中所述的C1-6烷基可选地由一个或多个取代基选自芳基、杂芳基、R10和A组成，所述的杂芳基可选地由一个或多个R10基团取代；其中所述的C3-6杂环烷基可选地包含一个或多个选自氧、硫、氮和CO的基团；R3是C1-6烷基，可选地被一个或多个取代基选自芳基、杂芳基、-NR4R5、-OR6、-NR7(CO)R6、-NR7(CO)NR4R5、-NR7SO2R6、-NR7COOR7、-CONR4R5、C3-6杂环烷基和其中R4-7和A如权利要求所定义。 进一步的方面涉及所述化合物在治疗各种治疗性疾病中的应用，特别是作为一个或多个激酶的抑制剂。
• The discovery of novel N-(2-pyrimidinylamino) benzamide derivatives as potent hedgehog signaling pathway inhibitors
  作者：Minhang Xin、Jun Wen、Feng Tang、Chongxing Tu、Han Shen、Xinge Zhao

  DOI：10.1016/j.bmcl.2013.10.022

  日期：2013.12

  Hedgehog signaling pathway inhibitors are emerging as new therapeutic intervention against cancer. A novel series of N-(2-pyrimidinylamino) benzamide derivatives as hedgehog signaling pathway inhibitors were designed and synthesized. Most compounds presented significant inhibitory effect on hedgehog signaling pathway, among which 21 compounds exhibited more potent than vismodegib. Furthermore, compound 6a showed moderate pharmacokinetic properties in vivo, representing a promising lead compound for further exploration. (C) 2013 Elsevier Ltd. All rights reserved.