(5-cyano-pyrazin-2-yl)-carbamic acid phenyl ester | 660851-49-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (5-cyano-pyrazin-2-yl)-carbamic acid phenyl ester
• 英文别名: (5-cyanopyrazin-2-yl)carbamic acid phenyl ester；phenyl 5-cyano-2-pyrazinylcarbamate；Phenyl 5-cyanopyrazin-2-ylcarbamate；phenyl N-(5-cyanopyrazin-2-yl)carbamate
• CAS: 660851-49-0
• 化学式: C₁₂H₈N₄O₂
• 分子量: 240.221
• InChiKey: FMDUIXVUAMELIC-UHFFFAOYSA-N

物化性质

• 沸点：
  413.7±45.0 °C(Predicted)
• 密度：
  1.38±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  87.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (5-cyano-pyrazin-2-yl)-carbamic acid phenyl ester 在 甲醇 、 tin(ll) chloride 作用下， 以 甲苯 为溶剂， 反应 14.0h， 生成 1-(4-Amino-5-chloro-2-methoxyphenyl)-3-(5-cyanopyrazin-2-yl)urea
  参考文献：
  名称：

  Synthesis and biological evaluation of 1-(2,4,5-trisubstituted phenyl)-3-(5-cyanopyrazin-2-yl)ureas as potent Chk1 kinase inhibitors

  摘要：

  Based on the X-ray crystallography of our lead compound 1-(5-chloro-2,4-dimethoxyphenyl)-3-(5-cyanopyrazin-2-yl) Urea ill the checkpoint kinase 1 (Chk1) enzyme, we modified R-4, and to a lesser extent, R-2, and R-5 of the phenyl ring, and made a variety of N-aryl-N'-pyrazinylurea Chk1 inhibitors. Enzymatic activity less than 20 nM was observed in 15 of 41 compounds. Compound 8i provided the best overall results in the cellular assays as it abrogated doxorubicin-induced cell cycle arrest (IC50=1.7 mu M) and enhanced doxorubicin cytotoxicity (IC50=0.44 mu M) while displaying no single agent activity. (C) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.01.028
• 作为产物：
  描述：

  2-氨基-5-氰基吡嗪 、 氯甲酸苯酯 生成 (5-cyano-pyrazin-2-yl)-carbamic acid phenyl ester
  参考文献：
  名称：

  N-OXIDES OF DIARYLUREA DERIVATIVES AND THEIR USE AS Chk1 INHIBITORS FOR THE TREATMENT OF CANCER

  摘要：

  该发明提供了一种Chk-1激酶抑制化合物，其化学式为(I)或其盐，溶剂合物或互变异构体，其中：G为CH2，O，NH，NHCO或CONH; A是(CH2)n基团，其中n为1至4，但当G为O或NH时，n至少为2; X1为氮或CH; X2为氮或CR5基团; X3为氮或CR5基团; X4为氮或CH; 前提是X2、X3和X4中不超过两个为氮; R1、R2、R3、R4、R5和R6如所述。

  公开号：

  US20090270416A1

文献信息

• Urea kinase inhibitors
  申请人：——

  公开号：US20040034038A1

  公开（公告）日：2004-02-19

  Compounds having the formula 1 are useful for inhibiting protein kinases. Also disclosed are methods of making the compounds, compositions containing the compounds, and methods of treatment using the compounds.

  具有公式1的化合物对抑制蛋白激酶很有用。还公开了制备这些化合物的方法、含有这些化合物的组合物以及使用这些化合物的治疗方法。
• [EN] PHARMACEUTICALLY ACTIVE PYRAZINE DERIVATIVES<br/>[FR] DÉRIVÉS PYRAZINE PHARMACEUTIQUEMENT ACTIFS
  申请人：SENTINEL ONCOLOGY LTD

  公开号：WO2013072502A1

  公开（公告）日：2013-05-23

  The invention provides compounds which inhibit or modulate the activity of Chk-1 kinase and which are useful in the treatment of cancer. The compounds have the general formula (1) and salts, N-oxides and tautomers thereof, wherein m is 2, 3 or 4; n is 0 or 1; Q1 is selected from a bond; C(=O); S(O); SO2; and an alkylene chain of 1 to 4 carbon atoms in length between the moiety R4 and the nitrogen atom N, wherein (a) one or more of the 1 to 4 carbon atoms of the alkylene chain may optionally be substituted with one or two C1-4 alkyl groups; and/or (b) one carbon atom of the 1 to 4 carbon atoms of the alkylene chain may optionally be replaced by a cyclopropane-1,1 -diyl or 1,1-cyclobutanediyl group; and/or (c) one carbon atom of the 1 to 4 carbon atoms of the alkylene chain may optionally be replaced by C(=O), S(O), or SO2, provided that Q1 contains no more than one C(=O), S(O), or SO2 moiety; R1 is selected from hydrogen, methyl, chlorine and bromine; R2 is selected from hydrogen, methyl, methoxy and a group -(O)p-Q2-R5; R3 is selected from hydrogen, a group Hyd1, a group -O-Hyd1 and a group -(O)p-Q2-R5; provided that when one of R2 and R3 is -(O)p-Q2-R5, the other is selected from hydrogen, methoxy and methyl; and R4 is selected from amino, NH- Hyd2, N(Hyd2)2; and a non-aromatic carbocyclic or heterocyclic ring of 4 to 7 ring members containing 0, 1, 2 or 3 heteroatom ring members selected from O, N and S and oxidised forms thereof; the carbocyclic or heterocyclic ring being optionally substituted with one or two substituents R9. Also provided are pharmaceutical compositions containing the compounds and methods for making the compounds.

  该发明提供了一种抑制或调节Chk-1激酶活性的化合物，用于治疗癌症。这些化合物具有一般式(1)及其盐、N-氧化物和互变异构体，其中m为2、3或4；n为0或1；Q1从键中选择；C(=O)；S(O)；SO2；以及在基团R4和氮原子N之间长度为1到4个碳原子的烷基链中选择的一个烷基链，其中(a)烷基链的1到4个碳原子中的一个或多个可选择地被一个或两个C1-4烷基基团取代；和/或(b)烷基链的1到4个碳原子中的一个碳原子可选择地被环丙烷-1,1-二基或1,1-环丁二基基团取代；和/或(c)烷基链的1到4个碳原子中的一个碳原子可选择地被C(=O)、S(O)或SO2取代，前提是Q1不含多于一个C(=O)、S(O)或SO2基团；R1从氢、甲基、氯和溴中选择；R2从氢、甲基、甲氧基和一个基团-(O)p-Q2-R5中选择；R3从氢、基团Hyd1、基团-O-Hyd1和基团-(O)p-Q2-R5中选择；前提是当R2和R3中的一个为-(O)p-Q2-R5时，另一个从氢、甲氧基和甲基中选择；R4从氨基、NH-Hyd2、N(Hyd2)2；和含有0、1、2或3个异原子环成员（O、N和S）及其氧化形式的非芳香碳环或杂环，环可选择地用一个或两个取代基R9取代。还提供了含有这些化合物的药物组合物和制备这些化合物的方法。
• Pharmaceutically Active Pyrazine Derivatives
  申请人：Sentinel Oncology Limited

  公开号：US20140323484A1

  公开（公告）日：2014-10-30

  The invention provides compounds which inhibit or modulate the activity of Chk-1 kinase and which are useful in the treatment of cancer. The compounds have the general formula (1): and salts, N-oxides and tautomers thereof, wherein m is 2, 3 or 4; n is 0 or 1; Q 1 is selected from a bond; C(═O); S(O); SO 2 ; and an alkylene chain of 1 to 4 carbon atoms in length between the moiety R 4 and the nitrogen atom. N, wherein (a) one or more of the 1 to 4 carbon atoms of the alkylene chain may optionally be substituted with one or two C 1-4 alkyl groups; and/or (b) one carbon atom of the 1 to 4 carbon atoms of the alkylene chain may optionally be replaced by a cyclopropane-1,1-diyl or 1,1-cyclobutanediyl group; and/or (c) one carbon atom of the 1 to 4 carbon atoms of the alkylene chain may optionally be replaced by C(═O), S(O), or SO 2 , provided that Q 1 contains no more than one C(═O), S(O), or SO 2 moiety; R 1 is selected from hydrogen, methyl, chlorine and bromine; R 2 is selected from hydrogen, methyl, methoxy and a group —(O) p -Q 2 -R 5 ; R 3 is selected from hydrogen, a group Hyd 1 , a group —O-Hyd 1 and a group —(O) p -Q 2 -R 5 ; provided that when one of R 2 and R 3 is —(O) p -Q 2 -R 5 , the other is selected from hydrogen, methoxy and methyl; and R 4 is selected from amino, NH-Hyd 2 , N(Hyd 2 ) 2 ; and a non-aromatic carbocyclic or heterocyclic ring of 4 to 7 ring members containing 0, 1, 2 or 3 heteroatom ring members selected from O, N and S and oxidised forms thereof; the carbocyclic or heterocyclic ring being optionally substituted with one or two substituents R 9 . Also provided are pharmaceutical compositions containing the compounds and methods for making the compounds.

  该发明提供了抑制或调节Chk-1激酶活性的化合物，适用于癌症治疗。这些化合物具有一般式（1）：和其盐、N-氧化物和互变异构体，其中m为2、3或4；n为0或1；Q1选自键；C(═O)；S(O)；SO2；和长度为1至4个碳原子的烷基链，该链位于基团R4和氮原子之间。N，其中（a）烷基链的1至4个碳原子中的一个或多个可选择地被一个或两个C1-4烷基基团取代；和/或（b）烷基链的1至4个碳原子中的一个碳原子可选择地被环丙烷-1,1-二基或1,1-环丁烷二基团取代；和/或（c）烷基链的1至4个碳原子中的一个碳原子可选择地被C(═O)、S(O)或SO2取代，前提是Q1不含多于一个C(═O)、S(O)或SO2基团；R1选自氢、甲基、氯和溴；R2选自氢、甲基、甲氧基和基团—(O)p-Q2-R5；R3选自氢、基团Hyd1、基团—O-Hyd1和基团—(O)p-Q2-R5；前提是当R2和R3中的一个是—(O)p-Q2-R5时，另一个选自氢、甲氧基和甲基；R4选自氨基、NH-Hyd2、N(Hyd2)2；和含有0、1、2或3个杂原子环成员（O、N和S及其氧化形式）的非芳香碳环或杂环，环可选择地被一个或两个取代基R9取代。还提供了含有这些化合物的药物组合物和制备这些化合物的方法。
• [EN] UREA DERIVATIVES AS KINASE INHIBITORS<br/>[FR] DERIVES D'UREE COMME INHIBITEURS DE KINASE
  申请人：ABBOTT LAB

  公开号：WO2004014876A1

  公开（公告）日：2004-02-19

  Compounds having the formula are useful for inhibiting protein kinases. Also disclosed are methods of making thecompounds, compositions containing the compounds, and methods of treatment using the compounds.

  具有公式的化合物对于抑制蛋白激酶非常有用。还揭示了制备该化合物的方法，含有该化合物的组合物，以及使用该化合物进行治疗的方法。
• PHARMACEUTICAL COMPOUNDS
  申请人：Boyle Robert George

  公开号：US20130065900A1

  公开（公告）日：2013-03-14

  The invention provides a compound of the formula (1): or a salt, N-oxide or tautomer thereof; wherein R 1 is cyano or C 1-4 alkyl; R 2 is hydrogen or C 1-4 alkyl; R 3 is hydrogen or C 1-4 alkyl; R 4 and R 5 are the same or different and each is selected from hydrogen, saturated C 1-4 hydrocarbyl and saturated C 1-4 hydrocarbyloxy; R 6 and R 7 are the same or different and each is selected from hydrogen, halogen, CN, C 1-4 alkyl and C 1-4 alkoxy wherein the C 1-4 alkyl and C 1-4 alkoxy are each optionally substituted with hydroxy, C 1-2 alkoxy or by one or more flourine atoms; R 8 is hydrogen or C 1-4 alkyl; Q is an alkylene chain of 1 to 4 carbon atoms in length between the moiety Ar and the nitrogen atom N, wherein one or more of the 1 to 4 carbon atoms of the alkylene chain may optionally be substituted with one or two C 1-4 alkyl groups, or wherein one carbon atom of the 1 to 4 carbon atoms of the alkylene chain may optionally be substituted with a group —CH 2 CH 2 — which together with the said one carbon atom forms a cyclopropyl group; m is 1, 2, 3 or 4; n is 0 or 1; and Ar is a monocyclic or bicyclic aryl or heteroaryl group of 5 to 10 ring members containing 0, 1, 2, 3 or 4 heteroatom ring members selected from O, N and S, the aryl or heteroaryl group being optionally substituted with one to four substituents R 13 as defined in the claims. The compounds are inhibitors of Chk-1 kinase and are active against cancers.

  本发明提供了化合物的公式（1）：或其盐，N-氧化物或互变异构体；其中R1是氰基或C1-4烷基；R2是氢或C1-4烷基；R3是氢或C1-4烷基；R4和R5相同或不同，每个都选择自氢，饱和的C1-4烃基和饱和的C1-4烃基氧；R6和R7相同或不同，每个都选择自氢，卤素，CN，C1-4烷基和C1-4烷氧，其中C1-4烷基和C1-4烷氧均可选地用羟基，C1-2烷氧或一个或多个氟原子取代；R8是氢或C1-4烷基；Q是长度为1到4个碳原子的烷基链，在基团Ar和氮原子N之间，其中1到4个碳原子中的一个或多个可以可选地用一个或两个C1-4烷基取代，或其中1个碳原子可以可选地用一个—CH2CH2—基团取代，与所述1个碳原子一起形成环丙基基团；m为1、2、3或4；n为0或1；Ar是一个含有0、1、2、3或4个杂环原子环成的5到10个环成员的单环或双环芳基或杂芳基，所述芳基或杂芳基可选地用一到四个定义如权利要求中所定义的取代基R13取代。这些化合物是Chk-1激酶的抑制剂，对癌症具有活性。