1-(5-chloroindol-2-ylsulfonyl)-4-(4-(6-oxo-1H-pyridazin-3-yl)benzoyl)piperazine

• 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: 1-(5-chloroindol-2-ylsulfonyl)-4-(4-(6-oxo-1H-pyridazin-3-yl)benzoyl)piperazine
• 英文别名: 6-[4-({4-[(5-Chloro-1H-indol-2-yl)sulphonyl]piperazin-1-yl}carbonyl)phenyl]-pyridazin-3-ol；3-[4-[4-[(5-chloro-1H-indol-2-yl)sulfonyl]piperazine-1-carbonyl]phenyl]-1H-pyridazin-6-one
• 化学式: C₂₃H₂₀ClN₅O₄S
• 分子量: 497.962
• InChiKey: ZPLTUPBBDQNKKK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  34
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  123
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-溴-2-(2-甲氧基乙氧基)乙烷 、 1-(5-chloroindol-2-ylsulfonyl)-4-(4-(6-oxo-1H-pyridazin-3-yl)benzoyl)piperazine 在 potassium carbonate 作用下， 以 DMF (N,N-dimethyl-formamide) 为溶剂， 反应 1.0h， 以36%的产率得到6-{4-[4-(5-chloro-1H-indole-2-sulphonyl)-piperazine-1-carbonyl]-phenyl}-2-(2-(2-methoxy-ethoxy)-ethyl)-2H-pyridazin-3-one
  参考文献：
  名称：

  [EN] NEW DERIVATIVES OF 6-4{4-[1H-INDOLE-2-SULPHONYL)-PIPERAZIN-1-CARBONYL-PHENYL]}PYRADIZIN-3-ONE
  [FR] NOUVEAU DERIVES DE 6-4{4-[1H-INDOLE-2-SULPHONYL)-PIPERAZIN-1-CARBONYL-PHENYL]}PYRADIZIN-3-ONE

  摘要：

  该发明涉及公式（I）的杂环衍生物，其中R2是氨基，羟基OR4基团或-Y-R5基团，其中R4是氢或C1-4烷基，Y是C1-4烷基烯，R5是氢，卤素，羟基，C1-2烷氧基，C1-2烷氧基C1-2烷氧基C1-4，或NR7R8基团，其中R7和R8分别选自氢，C1-2烷基，羟基C1-2烷基或烷氧基C1-2烷基，或R7和R8与它们连接的氮原子一起形成饱和的5-6成员杂环环，该环可选择性地包含额外的杂原子；n为一或二，每个R1独立选择自卤素，卤素C1-2烷基，羟基，羟基，氨基，C1-2烷基氨基或二C1-2二烷基氨基；或其药学上可接受的盐。这些化合物具有抗血栓和抗凝作用，因此在人类或动物治疗方法中有用。该发明还涉及制备这些杂环衍生物的方法，含有它们的药物组成物以及它们在制造用于产生抗血栓或抗凝作用的药物的制剂中的使用。

  公开号：

  WO2005065688A1

文献信息

• Heterocyclic derivatives which inhibit factor Xa
  申请人：AstraZeneca AB

  公开号：US20040266759A1

  公开（公告）日：2004-12-30

  The invention relates to heterocyclic derivatives of formula (I), or pharmaceutically-acceptable salts thereof, which possess antithrombotic and anticoagulant properties and are accordingly useful in methods of treatment of humans or animals. The invention also relates to processes for the preparation of the heterocyclic derivatives, to pharmaceutical compositions containing them and to their use in the manufacture of medicaments for use in the production of an antithrombotic or anticoagulant effect. 1

  本发明涉及公式（I）的杂环衍生物或其药学上可接受的盐，具有抗血栓和抗凝血性质，因此在人类或动物的治疗方法中有用。本发明还涉及制备杂环衍生物的过程，含有它们的制药组合物以及它们用于制造用于产生抗血栓或抗凝血效应的药物的用途。
• Heterocyclic Sulfonamide Derivatives As Inhibitors Of Factor Xa
  申请人：Alstermark Christer

  公开号：US20080221063A1

  公开（公告）日：2008-09-11

  The invention relates to heterocyclic derivatives of formula (I), Chemical formula should be inserted here. Please see paper copy wherein R 1 is hydrogen or C 1-3 alkyl; R 2 is selected from hydroxy, C 1-5 alkyl, carboxy, cyano, tetrazolyl, N—C 1-5 alkyltetrazolyl, oxazolyl, C 1-5 oxazolyl, isoxazolyl, C 1-5 isoxazolyl, hydroxyC 1-5 alkyl, carboxy C 1-5 alkyl, C 1-5 alkoxyoxo C 1-5 alkyl, carbamoyl, C 1-5 alkylcarbamoyl, di(C 1-5 alkyl)carbamoyl, C 1-5 alkylcarbamoyl C 1-4 alkyl, hydroxy C 1-5 alkylcarbamoyl, C 1-5 alkoxy C 1-5 alkylcarbamoyl; —C 1-5 alkyl-Y 1 , —COOCHR 17 R 18 and —CONR 17 R 18 ; and R 3 is hydrogen or halogen; or a pharmaceutically acceptable salt thereof, said compounds possess antithrombotic and anticoagulant properties and are accordingly useful in methods of treatment of humans or animals. The invention also relates to processes for the preparation of the compounds, to their use, to pharmaceutical compositions comprising them, to their use in the manufacture of medicaments for use in the production of an antithrombotic or anticoagulant effect, and to combinations comprising them.

  本发明涉及式（I）的杂环衍生物，化学式应在此处插入。请参阅纸质副本，其中R1是氢或C1-3烷基；R2选自羟基，C1-5烷基，羧基，氰基，四唑基，N- C1-5烷基四唑基，噁唑基，C1-5噁唑基，异噁唑基，C1-5异噁唑基，羟基C1-5烷基，羧基C1-5烷基，C1-5烷氧氧代C1-5烷基，氨基甲酰基，C1-5烷基氨基甲酰基，二（C1-5烷基）氨基甲酰基，C1-5烷基氨基甲酰基C1-4烷基，羟基C1-5烷基氨基甲酰基，C1-5烷氧基C1-5烷基氨基甲酰基；-C1-5烷基-Y1，-COOCHR17R18和CONR17R18；以及R3是氢或卤素；或其药学上可接受的盐，这些化合物具有抗血栓和抗凝血性质，因此在人类或动物的治疗方法中有用。本发明还涉及制备该化合物的方法，它们的用途，包括它们的制药组合物，用于制造用于产生抗血栓或抗凝血效应的药物的制剂以及包含它们的组合物。
• Heterocyclic Sulfonamide Derivatives as Inhibitors of Factor Xa
  申请人：Alstermark Christer

  公开号：US20080200431A1

  公开（公告）日：2008-08-21

  The invention relates to compounds of formula (I), Chemical formula should be inserted here. Please see paper copy wherein R 1 , R 2 , R 3 and R 4 are independently selected from carbon and nitrogen, and where is nitrogen; A 1 is a single bond or a double bond; n is 0, 1, 2 or 3; each R 5 is independently selected from hydrogen, halogen, C 1-3 alkyl, oxo, oxy, oxido and thioxo; R 6 is hydrogen or oxo; m is 0, 1, 2 or 3; A 2 is a single bond or a double bond; each R 7 is independently selected from hydrogen, hydroxy, oxo, C 1-5 alkyl, carboxy, cyano, tetrazolyl, N—C 1-5 alkyltetrazolyl, oxazolyl, C 1-5 oxazolyl, isoxazolyl, C 1-5 isoxazolyl, hydroxyC 1-5 alkyl, carboxy C 1-5 alkyl, C 1-5 alkoxyoxo C 1-5 alkyl, carbamoyl, C 1-5 alkylcarbamoyl, di(C 1-5 alkyl)carbamoyl, carbamoyl C 1-4 alkyl, C 1-5 alkylcarbamoyl C 1-4 alkyl, di(C 1-5 alkyl)carbamoyl C 1-4 alkyl, hydroxy C 1-5 alkylcarbamoyl, C 1-5 alkoxy C 1-5 alkylcarbamoyl, hydroxy C 1-5 alkylcarbamoyl C 1-4 alkyl, C 1-5 alkoxy C 1-5 alkylcarbamoyl C 1-4 alkyl, —CONR 8 (CH 2 ) x S(O) p R 9 , —CONH(CH 2 ) q NR 10 R 11 , —C 1-5 alkyl-Y 1 , —COOCHR 17 R 18 and —CONR 17 R 18 ; and R 30 is hydrogen, amino, methyl or halogen; or a pharmaceutically acceptable salt thereof, said compounds possess antithrombotic and anticoagulant properties and are accordingly useful in methods of treatment of humans or animals. The invention also relates to processes for the preparation of the compounds, to their use, to pharmaceutical compositions comprising them, to their use in the manufacture of medicaments for use in the production of an antithrombotic or anticoagulant effect, and to combinations comprising them.

  本发明涉及公式（I）的化合物，化学式应在此处插入。请参阅纸质副本，其中R1、R2、R3和R4独立地选择为碳和氮，其中氮；A1是单键或双键；n为0、1、2或3；每个R5独立地选择为氢、卤素、C1-3烷基、氧、氧化物、氧化物和硫代氧；R6是氢或氧；m为0、1、2或3；A2是单键或双键；每个R7独立地选择为氢、羟基、氧、C1-5烷基、羧基、氰基、四唑基、N- C1-5烷基四唑基、噁唑基、C1-5噁唑基、异噁唑基、C1-5异噁唑基、羟基C1-5烷基、羧基C1-5烷基、C1-5烷氧氧化C1-5烷基、氨基甲酰基、C1-5烷基甲酰基、二（C1-5烷基）甲酰基、氨基甲酰基C1-4烷基、C1-5烷基甲酰基C1-4烷基、二（C1-5烷基）甲酰基C1-4烷基、羟基C1-5烷基甲酰基、C1-5烷氧基C1-5烷基甲酰基、羟基C1-5烷基甲酰基C1-4烷基、C1-5烷氧基C1-5烷基甲酰基C1-4烷基、-CONR8（CH2）xS（O）pR9，-CONH（CH2）qNR10R11，-C1-5烷基-Y1，-COOCHR17R18和-CONR17R18；R30是氢、氨基、甲基或卤素；或其药学上可接受的盐，该化合物具有抗血栓和抗凝作用，因此在人或动物的治疗方法中有用。本发明还涉及制备该化合物的方法，它们的用途，包含它们的制药组合物，用于制造用于产生抗血栓或抗凝作用的药物的制剂的用途，以及包含它们的组合物。
• New derivatives of 6-{4-[4-(1h-indole-2-sulphonyl)-piperazin-1-carbonyl-phenyl]}pyradizin-3-one
  申请人：Bratt Emma

  公开号：US20070135441A1

  公开（公告）日：2007-06-14

  The invention relates to heterocyclic derivatives of formula (I), wherein R 2 is amino, a group OR 4 or a group —Y—R 5 where R 4 is hydrogen or C 1-4 alkyl, Y is C 1-4 alkylene, R 5 is hydrogen, halo, hydroxy, C 1-2 alkoxy, C 1-2 alkoxyC 1-2 alkoxyC 1-4 , or a group NR 7 R 8 where R 7 and R 8 are independently selected from hydrogen, C 1-2 alkyl, hydroxyC 1-2 alkyl or alkoxyC 1-2 alkyl, or R 7 and R 8 together with the nitrogen atom to which they are attached form a saturated 5-6-membered heterocyclic ring which optionally contains an additional heteroatom; n is one or two and each R 1 is independently selected from halo, haloC 1-2 alkyl, hydroxy, oxo, amino C 1-2 alkylamino or di-C 1-2 dialkylamino; or a pharmaceutically acceptable salt thereof. These compounds possess antithrombotic and anticoagulant properties and are accordingly useful in methods of treatment of humans or animals. The invention also relates to processes for the preparation of the heterocyclic derivatives, to pharmaceutical compositions containing them and to their use in the manufacture of medicaments for use in the production of an antithrombotic or anticoagulant effect.

  本发明涉及式(I)的杂环衍生物，其中R2是氨基，OR4基团或-Y-R5基团，其中R4是氢或C1-4烷基，Y是C1-4亚烷基，R5是氢，卤素，羟基，C1-2烷氧基，C1-2烷氧基C1-2烷氧基C1-4，或NR7R8基团，其中R7和R8各自选自氢，C1-2烷基，羟基C1-2烷基或烷氧基C1-2烷基，或R7和R8与它们所连接的氮原子一起形成一个饱和的5-6元杂环环，其中可以含有一个额外的杂原子；n是1或2，每个R1独立地选自卤素，卤素C1-2烷基，羟基，氧代，氨基C1-2烷基氨基或二C1-2二烷基氨基；或其药学上可接受的盐。这些化合物具有抗血栓和抗凝作用，因此在人类或动物的治疗方法中有用。本发明还涉及制备这些杂环衍生物的方法，含有它们的药物组合物以及它们在制造用于产生抗血栓或抗凝效果的药物的制剂中的使用。
• Derivatives of 6-{4-[4-(1H-indole-2-sulphonyl)-piperazin-1-carbonyl-phenyl]}pyradizin-3-one
  申请人：AstraZeneca AB

  公开号：US07419979B2

  公开（公告）日：2008-09-02

  The invention relates to heterocyclic derivatives of formula (I), wherein R2 is amino, a group OR4 or a group —Y—R5 where R4 is hydrogen or C1-4alkyl, Y is C1-4alkylene, R5 is hydrogen, halo, hydroxy, C1-2alkoxy, C1-2alkoxyC1-2alkoxyC1-4, or a group NR7R8 where R7 and R8 are independently selected from hydrogen, C1-2alkyl, hydroxyC1-2alkyl or alkoxyC1-2alkyl, or R7 and R8 together with the nitrogen atom to which they are attached form a saturated 5-6-membered heterocyclic ring which optionally contains an additional heteroatom; n is one or two and each R1 is independently selected from halo, haloC1-2alkyl, hydroxy, oxo, amino, C1-2alkylamino or di-C1-2dialkylamino; or a pharmaceutically acceptable salt thereof. These compounds possess antithrombotic and anticoagulant properties and are accordingly useful in methods of treatment of humans or animals. The invention also relates to processes for the preparation of the heterocyclic derivatives, to pharmaceutical compositions containing them and to their use in the manufacture of medicaments for use in the production of an antithrombotic or anticoagulant effect.

  本发明涉及式(I)的杂环衍生物，其中R2是氨基，OR4基团或-Y-R5基团，其中R4是氢或C1-4烷基，Y是C1-4烷基，R5是氢，卤素，羟基，C1-2烷氧基，C1-2烷氧基C1-2烷氧基C1-4，或NR7R8基团，其中R7和R8独立地选自氢，C1-2烷基，羟基C1-2烷基或烷氧基C1-2烷基，或R7和R8与它们所连接的氮原子一起形成饱和的5-6元杂环环，该环可以选择性地含有一个额外的杂原子；n为一或二，每个R1独立地选自卤素，卤素C1-2烷基，羟基，羰基，氨基，C1-2烷基氨基或二C1-2二烷基氨基；或其药学上可接受的盐。这些化合物具有抗血栓和抗凝血特性，因此可用于人类或动物的治疗方法。本发明还涉及制备杂环衍生物的方法，包含它们的制药组合物以及它们在制造具有抗血栓或抗凝血作用的药物的生产中的使用。