1-(5-chloroindol-2-ylsulphonyl)-piperazine | 249292-34-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 1-(5-chloroindol-2-ylsulphonyl)-piperazine
• 英文别名: 1-[(5-chloroindol-2-yl)sulfonyl]piperazine；5-chloro-2-(piperazin-1ylsulphonyl)-1H-indole；5-chloro-2-(piperazine-1-sulfonyl)-1H-indole；5-chloro-2-(piprazin-1ylsulphonyl)-1H-indole；1-(5-chloroindol-2-ylsulphonyl) piperazine；1-(5-chloroindol-2-ylsulphonyl)piperazine；5-chloro-2-piperazin-1-ylsulfonyl-1H-indole
• CAS: 249292-34-0
• 化学式: C₁₂H₁₄ClN₃O₂S
• 分子量: 299.781
• InChiKey: MFNBATKKWHPSIT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  73.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(5-chloroindol-2-ylsulphonyl)-piperazine 在 lithium hydroxide 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 2.92h， 生成 [4-[(5-chloro-1H-indol-2-yl)sulfonyl]piperazin-1-yl]-(5-methyl-6,7-dihydro-4H-[1,3]oxazolo[5,4-c]pyridin-2-yl)methanone
  参考文献：
  名称：

  新型Xa因子抑制剂的设计，合成和生物学活性：通过S1和S4配体修饰提高代谢稳定性。

  摘要：

  在大鼠中口服给药时，丝氨酸蛋白酶因子xa（fXa）抑制剂1表现出良好的离体抗fXa活性。但是，已经发现1对人肝微粒体的代谢稳定性低。为了改善代谢稳定性，我们尝试修饰1的S1和S4配体。这些修饰产生了化合物34b，该化合物具有选择性的抗fXa活性和出色的抗凝血活性。

  DOI：

  10.1016/j.bmc.2005.09.056
• 作为产物：
  描述：

  1-(苯磺酰基)-5-氯吲哚 在 sodium hydroxide 、 叔丁基锂 、 三乙胺 作用下， 以 甲醇 、 乙醚 、 二氯甲烷 、 正戊烷 为溶剂， 反应 23.5h， 生成 1-(5-chloroindol-2-ylsulphonyl)-piperazine
  参考文献：
  名称：

  Design, synthesis, and biological activity of non-basic compounds as factor Xa inhibitors: SAR study of S1 and aryl binding sites

  摘要：

  Compound 7 was identified as the active metabolite of 6 by HPLC and mass spectral analysis. Modification of lead compound 7 by transformation of its N-oxide 6-6 biaryl ring system and fused aromatics produced a series of non-basic fxa inhibitors with excellent potency in anti-fXa and anticoagulant assays. The optimized compounds 73b and 75b showed sub to one digit micromolar anticoagulant activity (PTCT2). Particularly, anti-fXa activity was detected in plasma of rats orally administered with 1 mg/kg of compound 75b. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.04.006
• 作为试剂：
  描述：

  1-(1-Benzenesulphonyl-5-chloroindol-2-ylsulphonyl)piperazine 、 sodium hydroxide 、 盐酸 在 1-(5-chloroindol-2-ylsulphonyl)-piperazine 、 resultant precipitate 、 水 作用下， 反应 0.75h， 以to give 1-(5-chloroindol-2-ylsulphonyl)piperazine as a pale yellow solid, 1H NMR (d6DMSO) 2.75 ppm (m, 4H), 2.9 ppm (m, 4H), 7.0 ppm (s, 1H), 7.3 ppm (dd, 1H), 7.5 ppm (d, 1H), 7.8 ppm (d, 1H)的产率得到1-(5-chloroindol-2-ylsulphonyl)-piperazine
  参考文献：
  名称：

  Heterocyclic derivatives which inhibit factor Xa

  摘要：

  本发明涉及公式（I）的杂环衍生物或其药学上可接受的盐，其具有抗血栓和抗凝血性能，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方法、含有它们的制药组合物以及它们在制造用于产生抗血栓或抗凝血效应的药物的过程中的使用。

  公开号：

  US06753331B1

文献信息

• NOVEL SULFONYL DERIVATIVES
  申请人：DAIICHI PHARMACEUTICAL CO., LTD.

  公开号：EP1104754A1

  公开（公告）日：2001-06-06

  Sulfonyl derivatives represented by the following general formula (I): Q1-Q2-T1-Q3-SO2-QA and drugs containing the same (wherein Q1 is an optionally substituted, saturated or unsaturated, five- or six-membered cyclic hydrocarbon group, a five- or six-membered heterocyclic group, or the like; Q2 is a single band, oxygen, sulfur, C1-C6 alkylene or the like; QA is optionally substituted arylalkenyl, heteroarylalkenyl or the like; and T1 is carbonyl or the like). These compounds have potent FXa-inhibitory effects and promptly exert satisfactory and persistent antithrombotic effects through oral administration, thus being useful as anticoagulant agents little accompanied with side effects.

  以下是通用公式（I）所代表的磺酰衍生物：Q1-Q2-T1-Q3-SO2-QA以及含有这些衍生物的药物（其中Q1是可选择地取代的饱和或不饱和的五元或六元环烃基团，五元或六元杂环基团等；Q2是单键，氧，硫，C1-C6烷基或类似物；QA是可选择地取代的芳基烯烃基团，杂环芳基烯烃基团或类似物；T1是羰基或类似物）。这些化合物具有强大的FXa抑制作用，并通过口服迅速产生令人满意且持久的抗血栓作用，因此可作为几乎不伴随副作用的抗凝血剂。
• [EN] NEW DERIVATIVES OF 6-4{4-[1H-INDOLE-2-SULPHONYL)-PIPERAZIN-1-CARBONYL-PHENYL]}PYRADIZIN-3-ONE<br/>[FR] NOUVEAU DERIVES DE 6-4{4-[1H-INDOLE-2-SULPHONYL)-PIPERAZIN-1-CARBONYL-PHENYL]}PYRADIZIN-3-ONE
  申请人：ASTRAZENECA AB

  公开号：WO2005065688A1

  公开（公告）日：2005-07-21

  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.

  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。
• Novel sulfonyl derivatives
  申请人：DAIICHI PHARMACEUTICAL CO., LTD.

  公开号：US20040082611A1

  公开（公告）日：2004-04-29

  Described in the present invention are a sulfonyl derivative represented by the following formula (I): Q 1 -Q 2 -T 1 -Q 3 -SO 2 -Q A (I) [wherein Q 1 represents a saturated or unsaturated 5- or 6-membered cyclic hydrocarbon group, 5- or 6-membered heterocyclic group, dicyclic fused ring or tricyclic fused ring group which may have a substituent; Q 2 represents a single bond, an oxygen atom, a sulfur atom, a linear or branched C 1-6 alkylene group or the like; Q A represents an arylalkenyl group which may have a substituent or a heteroarylalkenyl group which may have a substituent; and T 1 represents a carbonyl group or the like] and a medicament comprising the same. The compound has strong FXa inhibitory action, provides prompt, sufficient and long-lasting anti-thrombus effects when orally administered, and has low side effects and is therefore useful as an excellent anticoagulant.

  本发明描述了一种由以下式(I)表示的磺酰基衍生物： Q1-Q2-T1-Q3-SO2-QA(I) [其中，Q1表示饱和或不饱和的5-或6-环烃基、5-或6-杂环基、二环融合环或三环融合环基，可能具有取代基；Q2表示单键、氧原子、硫原子、线性或支链的C1-6烷基等；QA表示可能具有取代基的芳基烯基或杂芳基烯基；T1表示羰基基团或类似物]，以及包含该化合物的药物。该化合物具有强烈的FXa抑制作用，口服后提供快速、充分和持久的抗血栓效果，并且具有低副作用，因此可用作优秀的抗凝剂。
• Heterocyclic Sulfonamide Derivatives as Inhibitors of Factor Xa
  申请人：Alstermark Christer

  公开号：US20080214495A1

  公开（公告）日：2008-09-04

  The invention relates to compounds of formula (I), wherein R 1 and R 3 are independently selected from carbon and nitrogen; R 2 is oxo or thioxo; n is 0, 1 or 2; each R 10 is independently selected from hydrogen and C 1-3 alkyl; R 4 and R 5 are each selected from carbon and nitrogen, wherein at least one of R 4 and R 5 is nitrogen; R 6 is hydrogen or oxo; R 7 is an aliphatic, partially saturated or aromatic carbocyclic ring, said carbocyclic ring having 0, 1 or 2 hetero nitrogen; m is 0, 1 or 2; each R 11 is independently selected from hydrogen, hydroxy, oxo, C 1-5 alkyl, carboxy, hydroxyC 1-5 alkyl, carboxyC 1-5 alkyl, C 1-5 alkoxy-oxoC 1-5 alkyl, carbamoyl, C 1-5 alkylcarbamoyl, di (C 1-5 alkyl)carbamoyl, carbamoylC 1-4 alkyl,C 1-5 alkylcarbamoylC 1-4 alkyl, di(C 1-5 alkyl)carbamoylC 1-4 alkyl, hydroxyC 1-5 alkylcarbamoyl, C 1-5 alkoxyC 1-5 alkylcarbamoyl, hydroxyC 1-5 alkylcarbamoylC 1-4 alkyl, C 1-5 alkoxyC 1-5 alkylcarbamoylC 1-4 alkyl, CONR 80 (CH 2 ) x S(O) p R90, CONH(CH 2 ) q NR 100 R 100 , —C 1-5 alkyl-Y 1 , —COOCHR 170 R 180 and —CON R 170 R 180 ; R 8 is a bond, C 1-4 alkylene or C 2-6 alkenylene; R 9 is an aromatic ring system having 0, 1 or 2 hetero atoms; wherein R 9 is substituted by 0 or 1 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)的化合物，其中R1和R3独立选择自碳和氮；R2为氧或硫氧；n为0、1或2；每个R10独立选择自氢和C1-3烷基；R4和R5各自选择自碳和氮，其中至少一个是氮；R6为氢或氧；R7为脂肪族、部分饱和或芳香碳环，所述碳环具有0、1或2个杂原子氮；m为0、1或2；每个R11独立选择自氢、羟基、氧、C1-5烷基、羧基、羟基C1-5烷基、羧基C1-5烷基、C1-5烷氧基-氧代C1-5烷基、氨基、C1-5烷基氨基、二(C1-5烷基)氨基、氨基C1-4烷基、C1-5烷基氨基C1-4烷基、二(C1-5烷基)氨基C1-4烷基、羟基C1-5烷基氨基、C1-5烷氧基C1-5烷基氨基、羟基C1-5烷基氨基C1-4烷基、C1-5烷氧基C1-5烷基氨基C1-4烷基、CONR80(CH2)xS(O)pR90、CONH(CH2)qNR100R100、-C1-5烷基-Y1、-COOCHR170R180和-CON R170R180；R8为键、C1-4烷基或C2-6烯基；R9为具有0、1或2个杂原子的芳香环系；其中R9由0或1个卤素取代；或其药学上可接受的盐，所述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效应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。