2-(5-chlorothien-2-yl)ethanesulfonyl chloride | 553653-40-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 英文名称: 2-(5-chlorothien-2-yl)ethanesulfonyl chloride
• 英文别名: (E)-2-(5-chloro-2-thienyl)ethanesulfonyl chloride；2-(5-chloro-2-thienyl)ethanesulfonyl chloride；2-(5-chlorothiophen-2-yl)ethanesulfonyl chloride
• CAS: 553653-40-0
• 化学式: C₆H₆Cl₂O₂S₂
• mdl: MFCD19200160
• 分子量: 245.15
• InChiKey: FAJORQTXBLZMPW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  12
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.333
• 拓扑面积：
  70.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(5-chlorothien-2-yl)ethanesulfonyl chloride 在 4-二甲氨基吡啶 、 盐酸羟胺 、 三乙胺 、 potassium hydroxide 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 0.1h， 生成 2-(2-(5-chlorothiophen-2-yl)ethylsulfonamido)-N-hydroxyacetamide
  参考文献：
  名称：

  Discovery of a New Class of Potent MMP Inhibitors by Structure-Based Optimization of the Arylsulfonamide Scaffold

  摘要：

  A new class of potent matrix metalloproteinase (MMP) inhibitors designed by structure-based optimization of the well-known arylsulfonamide scaffold is presented. Molecules show an ethylene linker connecting the sulfonamide group with P1' aromatic portion and a D-proline residue bearing the zinc-binding group. The affinity improvement providing by these modifications led us to discover a nanomolar MMP inhibitor bearing a carboxylate moiety as zinc-binding group, which might be a promising lead molecule. Notably, a significant selectivity for MMP-8, MMP-12, and MMP-13 was observed with respect to MMP-1 and MMP-7.

  DOI：

  10.1021/ml300446a
• 作为产物：
  描述：

  2-(5-chlorothiophen-2-yl)ethanol 在 四溴化碳 、 三苯基膦 、 sodium sulfite 、 三氯氧磷 作用下， 以 四氢呋喃 、 水 、 丙酮 为溶剂， 生成 2-(5-chlorothien-2-yl)ethanesulfonyl chloride
  参考文献：
  名称：

  Selective and dual action orally active inhibitors of thrombin and factor Xa

  摘要：

  The synthetic entry to new classes of dual fXa/thrombin and selective thrombin inhibitors with significant oral bioavailability is described. This was achieved through minor modifications to the sulfonamide group in our potent and selective fXa inhibitor (E)-2-(5-chlorothien-2-yl)-N-{(3S)-1-[(1S)-1-methyl-2-(morpholin-4-yl)-2-oxoethyl]-2-oxopyrrolidin-3-yl}ethenesulfonamide and these observed activity changes have been rationalised using structural studies.

  DOI：

  10.1016/j.bmcl.2007.03.080

文献信息

• [EN] PYRROLYDIN-2-ONE DERIVATIVES AS INHIBITORS OF THROMBIN AND FACTOR XA<br/>[FR] DERIVES DE PYRROLYDIN-2-ONE UTILISES COMME INHIBITEURS DE LA THROMBINE ET DU FACTEUR XA
  申请人：GLAXO GROUP LTD

  公开号：WO2004052851A1

  公开（公告）日：2004-06-24

  The invention relates to compounds of formula (I), wherein : R1 represents hydrogen, C1-4 alkyl, -CH2CO2H, -CH2CO2C1-2alkyl, or -CH2CONR7R8; R2 and R3 independently represent hydrogen, -C1-6alkyl, -C1-3alkylCN, -C1-3alkylCO2H, -C1-4alkylOC1-4alkyl, -C1-4alkylS(O)nC1-4alkyl, -C1-4alkylNR10R11, -C1-3alkylNCO2C1-4alkyl, -C1-3alkylCONR7R8, -C1-3alkylCO2C0-2alkylR9, -C1-3alkylCOC0-2alkylR9, -C1-3alkylCON(R8) C0-2 alkylR9, -C1-3alkylNCO2C0-2alkylR9, -C1-3alkylNCOC0-2alkylR9 or -C0-2alkylR9, with the proviso that one of R2 and R3 is hydrogen and the other is a substituent other than hydrogen; n is an integer between 0 and 2; R4 and R5 together with the nitrogen atom to which they are attached form a morpholino ring; R6 represents a group selected from formula (II) wherein T1 and T2 independently represent CH2, NH, S or O with the proviso that when one of T1 or T2 represents NH, S or O the other represents CH2; M represents CH3, -OH or PO; V represents CH or N; W represents H, CH3, Cl or F; X represents C1, Br, F or -CH3; Y represents CH3 or CF3; Z represents -CH3 or F; R7 and R8 are independently hydrogen, C1-4alkyl or together with the N atom to which they are bonded form a 5- or 6- membered non-aromatic heterocyclic ring, optionally containing an additional heteroatom selected from O, N or S; R10 and R11 independently represent C1-4alkyl or together with the N atom towhich they are bonded form a 5- or 6- membered non-aromatic heterocyclic ring, optionally containing an additionalheteroatom selected from O, N or S; R9 represents phenyl or a 5- or 6- membered aromatic or non-aromatic heterocyclic group, containing at least one heteroatom selected from O, N or S, each of which is optionally substituted by 0-2 groups selected from: C1-3alkyl or halogen; and pharmaceutically acceptable derivatives thereof, processes for their preparation, pharmaceutical compositions containing them and to their use in medicine, particularly use in the amelioration of a clinical condition for which a thrombin inhibitor is indicated.

  该发明涉及式(I)的化合物，其中：R1代表氢，C1-4烷基，-CH2CO2H，-CH2CO2C1-2烷基，或-CH2CONR7R8；R2和R3独立地代表氢，-C1-6烷基，-C1-3烷基CN，-C1-3烷基CO2H，-C1-4烷基OC1-4烷基，-C1-4烷基S(O)nC1-4烷基，-C1-4烷基NR10R11，-C1-3烷基NCO2C1-4烷基，-C1-3烷基CONR7R8，-C1-3烷基CO2C0-2烷基R9，-C1-3烷基COC0-2烷基R9，-C1-3烷基CON(R8) C0-2烷基R9，-C1-3烷基NCO2C0-2烷基R9，-C1-3烷基NCOC0-2烷基R9或-C0-2烷基R9，但要求R2和R3中的一个为氢，另一个为非氢取代基；n是0到2之间的整数；R4和R5与它们连接的氮原子一起形成吗啡环；R6代表从式(II)中选择的基团，其中T1和T2独立地代表CH2，NH，S或O，但要求当T1或T2代表NH，S或O时，另一个代表CH2；M代表CH3，-OH或PO；V代表CH或N；W代表H，CH3，Cl或F；X代表C1，Br，F或-CH3；Y代表CH3或CF3；Z代表-CH3或F；R7和R8独立地代表氢，C1-4烷基，或者与它们连接的N原子一起形成一个5-或6-成员非芳香杂环，选择性地包含另一个从O，N或S中选择的杂原子；R10和R11独立地代表C1-4烷基，或者与它们连接的N原子一起形成一个5-或6-成员非芳香杂环，选择性地包含另一个从O，N或S中选择的杂原子；R9代表苯基或一个5-或6-成员芳香或非芳香杂环基团，其中至少含有一个从O，N或S中选择的杂原子，每个基团选择性地被0-2个从C1-3烷基或卤素中选择的基团取代；以及其药用可接受的衍生物，其制备方法，含有它们的药物组合物以及在医学中的使用，特别是在改善需要凝血酶抑制剂的临床状况中的使用。
• [EN] N-(1-(2,3-DIHYDRO-1H-INDEN-5YL) -2-OXO-3-PYRROLIDINYL) -SULFONAMIDE DERIVATIVES FOR USE AS FACTOR XA INHIBITORS<br/>[FR] DERIVES DE N-(1-(2,3-DIHYDRO-1H-INDEN-5YL) -2-OXO-3-PYRROLIDINYL)-SULFONAMIDE UTILES EN TANT QU'INHIBITEURS DU FACTEUR XA
  申请人：GLAXO GROUP LTD

  公开号：WO2006027186A1

  公开（公告）日：2006-03-16

  The invention relates to at least one chemical entity chosen from compounds of formula (I): wherein: R1 represents a group selected from (II): each ring of which optionally contains a further heteroatom N, Z represents an optional substituent halogen, alk represents alkylene or alkenylene, T represents S, O or NH; R2 represents hydrogen, -C1-6alkyl, - C1-3alkyl CONRaRb, - C1-3alkyl CO2 C1-4alkyl, -CO2 C1-4alkyl or - C1-3alkyl CO2H; Ra and Rb independently represent hydrogen, - C1-6alkyl, or together with the N atom to which they are bonded form a 5-, 6- or 7- membered non-aromatic heterocyclic ring optionally containing an additional heteroatom selected from O, N and S, optionally substituted by C1-4alkyl, and optionally the S heteroatom is substituted by O, i.e. represents S(O)n; n represents 0-2; X represents an optional substituent on the indane ring selected from: halogen, - C1-4alkyl, -C2-4alkenyl and -CF3; Y represents a group -(CH2)mNRcRd substituted on the non-aromatic portion of the indane ring; Rc and Rd independently represent hydrogen, - C1-6alkyl, - C1-4alkylOH, or together with the N atom to which they are bonded form a 4-, 5-, 6- or 7- membered non-aromatic heterocyclic ring, the 5-, 6- or 7- membered non-aromatic heterocyclic ring optionally containing an additional heteroatom selected from O, N or S, and the 4-, 5-, 6- or 7- membered non-aromatic heterocyclic ring optionally substituted by C1-4alkyl or halogen; m represents 0-2; and pharmaceutically acceptable derivative(s) thereof. The invention also relates to processes for the preparation of compound(s) of formula (I), pharmaceutical compositions containing compound(s) of formula (I) and to the use of compound(s) of formula (I) in medicine, particularly in the amelioration of a clinical condition for which a Factor Xa inhibitor is indicated.

  该发明涉及至少一种化学实体，选择自化合物的公式（I）：其中：R1代表从（II）中选择的基团：每个环可选地含有进一步的杂原子N，Z代表可选的取代卤素，alk代表烷基或烯基，T代表S、O或NH；R2代表氢、-C1-6烷基、-C1-3烷基CONRaRb、-C1-3烷基CO2C1-4烷基、-CO2C1-4烷基或-C1-3烷基CO2H；Ra和Rb独立地代表氢、-C1-6烷基，或者与它们连接的N原子一起形成一个5、6或7-成员非芳香杂环，可选地含有另一个从O、N和S中选择的杂原子，可选地被C1-4烷基取代，且可选地S杂原子被O取代，即表示S（O）n；n代表0-2；X代表在茚环上的可选取代基，选择自：卤素、-C1-4烷基、-C2-4烯基和-CF3；Y代表取代在茚环非芳香部分上的群-(CH2)mNRcRd；Rc和Rd独立地代表氢、-C1-6烷基、-C1-4烷基OH，或者与它们连接的N原子一起形成一个4、5、6或7-成员非芳香杂环，5、6或7-成员非芳香杂环可选地含有另一个从O、N或S中选择的杂原子，4、5、6或7-成员非芳香杂环可选地被C1-4烷基或卤素取代；m代表0-2；及其药学上可接受的衍生物。该发明还涉及制备公式（I）化合物的方法，含有公式（I）化合物的药物组合物以及在医学上使用公式（I）化合物，特别是在改善适应于Xa因子抑制剂的临床病况方面。
• [EN] PYRROLIDINE - 2- ONES AS FACTOR XA INHIBITORS<br/>[FR] PYRROLYDINE-2-ONES COMME INHIBITEURS DU FACTEUR XA
  申请人：GLAXO GROUP LTD

  公开号：WO2004111045A1

  公开（公告）日：2004-12-23

  The invention relates to compounds of formula (I): wherein: R1 represents a group selected from: formula (II), each ring of which optionally contains a further heteroatom N, Z represents an optional substituent halogen, alk represents alkylene or alkenylene, T represents S, O or NH; R2 represents hydrogen, -C1-6alkyl, -C1-3alkylCONRaRb, -C1-3alkylCO2C1-4alkyl, -CO2C1-4alkyl or -C1-3alkylCO2H; Ra and Rb independently represent hydrogen, -C1-6alkyl, or together with the N atom to which they are bonded form a 5-, 6- or 7- membered non-aromatic heterocyclic ring optionally containing an additional heteroatom selected from O, N or S, optionally substituted by -C1-4alkyl, and optionally the S heteroatom is substituted by O, i.e. represents S(O)n; n represents 0-2; X represents phenyl or a 5- or 6- membered aromatic heterocyclic group containing at least one heteroatom selected from O, N or S, each of which is optionally substituted by 0-2 groups selected from: halogen, -C1-4alkyl, -C2-4alkenyl, -CN, -CF3, -NRaRb, -C0-4alkylORe, -C(O)Rf and -C(O)NRaRb; Re represents hydrogen or -C1-6alkyl; Rf represents -C1-6alkyl; Y represents phenyl or a 5- or 6- membered aromatic heterocyclic group containing at least one heteroatom selected from O, N or S, each of which is substituted by a group -C1-2alkylNRcRd. Rc and Rd, together with the nitrogen atom to which they are bonded, form a 4-membered heterocyclic ring optionally substituted by halogen, OH or -OC1-6alkyl, or a 5- or 6- membered non-aromatic heterocyclic ring substituted by OH, -OC1-6alkyl or 1 to 2 halogens, with the proviso that the substituent is not attached to a ring carbon atom adjacent to a heteroatom; and/or pharmaceutically acceptable derivatives thereof. The invention also relates to processes for the preparation of compounds of formula (I), pharmaceutical compositions containing compounds of formula (I) and to the use of compounds of formula (I) in medicine, particularly in the amelioration of a clinical condition for which a Factor Xa inhibitor is indicated.

  该发明涉及以下式(I)的化合物： 其中： R1代表从以下中选择的基团：式(II)，其中每个环可选地包含进一步的杂原子N，Z代表可选的取代卤素，alk代表烷基或烯基，T代表S，O或NH；R2代表氢，-C1-6烷基，-C1-3烷基CONRaRb，-C1-3烷基CO2C1-4烷基，-CO2C1-4烷基或-C1-3烷基CO2H；Ra和Rb独立地代表氢，-C1-6烷基，或者与它们连接的N原子一起形成一个5、6或7-成员非芳杂环，可选地含有另一个从O、N或S中选择的杂原子，可选地被-C1-4烷基取代，且可选地S杂原子被O取代，即表示S(O)n；n代表0-2；X代表苯基或含有至少一个从O、N或S中选择的杂原子的5-或6-成员芳香杂环基团，每个基团可选地被0-2个从以下中选择的基团取代：卤素，-C1-4烷基，-C2-4烯基，-CN，-CF3，-NRaRb，-C0-4烷基ORe，-C(O)Rf和-C(O)NRaRb；Re代表氢或-C1-6烷基；Rf代表-C1-6烷基；Y代表苯基或含有至少一个从O、N或S中选择的杂原子的5-或6-成员芳香杂环基团，每个基团被-C1-2烷基NRcRd取代。Rc和Rd，与它们连接的氮原子一起，形成一个可选地被卤素、OH或-OC1-6烷基取代的4-成员杂环基团，或者被OH、-OC1-6烷基或1到2个卤素取代的5-或6-成员非芳杂环基团，但前提是取代基未连接到相邻于杂原子的环碳原子；和/或其药学上可接受的衍生物。该发明还涉及制备上述式(I)化合物的方法，含有上述式(I)化合物的药物组合物，以及在医学上使用上述式(I)化合物，特别是在改善适应于Xa因子抑制剂的临床状况方面的用途。
• 1-Benzazepine-3-Sulfonylamino-2-Pyrroridones as Factor Xa Inhibitors
  申请人：Camus Laure

  公开号：US20080306045A1

  公开（公告）日：2008-12-11

  The invention relates to chemical entities of formula (I): and/or pharmaceutically acceptable derivative(s) thereof. The invention also relates to processes for the preparation of compounds of formula (I), pharmaceutical compositions containing compounds of formula (I) and to the use of compounds of formula (I) in medicine, particularly in the amelioration of a clinical condition for which a Factor Xa inhibitor is indicated.

  该发明涉及式(I)的化学实体和/或其药用可接受衍生物。该发明还涉及制备式(I)化合物的方法，含有式(I)化合物的药物组合物以及在医学中使用式(I)化合物，特别是在改善适用于Xa因子抑制剂的临床病况中的使用。
• [EN] PYRROLIDINE-2-ONES AS FACTOR XA INHIBITORS<br/>[FR] PYRROLIDINE-2-ONES UTILISEES COMME INHIBITEURS DU FACTEUR XA
  申请人：GLAXO GROUP LTD

  公开号：WO2003053925A1

  公开（公告）日：2003-07-03

  The invention relates to compounds of formula (I): , and pharmaceutically acceptable derivatives thereof. The invention also relates to processes for the preparation of compounds of formula (I), pharmaceutical compositions containing compounds of formula (I) and to the use of compounds of formula (I) in medicine, particularly in the amelioration of a clinical condition for which a Factor Xa inhibitor is indicated.

  该发明涉及式（I）的化合物，以及其药学上可接受的衍生物。该发明还涉及制备式（I）化合物的方法，含有式（I）化合物的药物组合物以及在医学上使用式（I）化合物，特别是在改善需要使用FXa抑制剂的临床病情方面的用途。