3-chloro-1-[tris(1-methylethyl)silyl]-1H-indole-6-sulfonyl chloride | 879500-15-9

• 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: 3-chloro-1-[tris(1-methylethyl)silyl]-1H-indole-6-sulfonyl chloride
• 英文别名: 3-chloro-1-(triisopropylsilyl)-1H-indole-6-sulfonyl chloride；3-chloro-1-tri(propan-2-yl)silylindole-6-sulfonyl chloride
• CAS: 879500-15-9
• 化学式: C₁₇H₂₅Cl₂NO₂SSi
• 分子量: 406.449
• InChiKey: GGQRZCMPHNDHPP-UHFFFAOYSA-N

物化性质

• 沸点：
  412.7±27.0 °C(Predicted)
• 密度：
  1.22±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.25
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  47.4
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (3S)-3-amino-1-[1-(dimethylamino)-2,3-dihydro-1H-inden-5-yl]-2-pyrrolidine 、 3-chloro-1-[tris(1-methylethyl)silyl]-1H-indole-6-sulfonyl chloride 在 吡啶 作用下， 以 乙腈 为溶剂， 生成 3-chloro-N-{(3S)-1-[1-(dimethylamino)-2,3-dihydro-1H-inden-5-yl]-2-oxo-3-pyrrolidinyl}-1-[tris(1-methylethyl)silyl]-1H-indole-6-sulfonamide
  参考文献：
  名称：

  Structure and property based design of factor Xa inhibitors: Pyrrolidin-2-ones with aminoindane and phenylpyrrolidine P4 motifs

  摘要：

  The rational design, syntheses and evaluation of potent sulfonamidopyrrolidin-2-one-based factor Xa inhibitors incorporating aminoindane and phenylpyrrolidine P4 motifs are described. These series delivered highly potent anticoagulant compounds with excellent oral pharmacokinetic profiles; however, significant time dependant P450 inhibition was an issue for the aminoindane series, but this was not observed with the phenylpyrrolidine motif, which produced candidate quality molecules with potential for once-daily oral dosing in humans. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.01.131
• 作为产物：
  描述：

  6-bromo-1-(triisopropylsilyl)-1H-indole 在 正丁基锂 、 磺酰氯 作用下， 以 四氢呋喃 、 hexanes 、 环己烷 为溶剂， 反应 3.5h， 生成 3-chloro-1-[tris(1-methylethyl)silyl]-1H-indole-6-sulfonyl chloride
  参考文献：
  名称：

  WO2006/108709

  摘要：

  公开号：

文献信息

• [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。
• 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。
• N-(1-(2,3-Dihydro-1H-Inden-5Yl)-2-Oxo-3-Pyrrolidinyl)-Sulfonamide Derivatives for Use as Factor Xa Inhibitors
  申请人：Harling David John

  公开号：US20070249705A1

  公开（公告）日：2007-10-25

  The invention relates to at least one chemical entity chosen from compounds of formula (I): 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.

  本发明涉及至少一种化学实体，所选实体为式（I）化合物和其药学上可接受的衍生物。本发明还涉及制备式（I）化合物的方法，含有式（I）化合物的药物组合物以及将式（I）化合物用于医学，特别是用于改善适应于Xa因子抑制剂的临床状况。
• 3-Sulfonylamino-Pyrrolidine-2-One Derivatives as Factor Xa Inhibitors
  申请人：Harling John David

  公开号：US20090099231A1

  公开（公告）日：2009-04-16

  The present invention provides pyrrolidinone derivatives as Factor Xa inhibitors and pharmaceutical compositions comprising the same. The invention also relates to processes for the preparation of such compounds, and the use of such compounds in medicine, particularly in the amelioration of a clinical condition for which a Factor Xa inhibitor is indicated.

  本发明提供吡咯烷酮衍生物作为因子Xa抑制剂，以及包含这些衍生物的药物组合物。本发明还涉及制备这些化合物的方法，以及在医学中使用这些化合物，特别是在改善需要因子Xa抑制剂的临床病况方面的使用。
• Structure and property based design of factor Xa inhibitors: Pyrrolidin-2-ones with aminoindane and phenylpyrrolidine P4 motifs
  作者：Robert J. Young、Carl Adams、Mike Blows、David Brown、Cynthia L. Burns-Kurtis、Chuen Chan、Laiq Chaudry、Máire A. Convery、David E. Davies、Anne M. Exall、Graham Foster、John D. Harling、Eric Hortense、Stephanie Irvine、Wendy R. Irving、Steve Jackson、Savvas Kleanthous、Anthony J. Pateman、Angela N. Patikis、Theresa J. Roethka、Stefan Senger、Gary J. Stelman、John R. Toomey、Robert I. West、Caroline Whittaker、Ping Zhou、Nigel S. Watson

  DOI：10.1016/j.bmcl.2011.01.131

  日期：2011.3

  The rational design, syntheses and evaluation of potent sulfonamidopyrrolidin-2-one-based factor Xa inhibitors incorporating aminoindane and phenylpyrrolidine P4 motifs are described. These series delivered highly potent anticoagulant compounds with excellent oral pharmacokinetic profiles; however, significant time dependant P450 inhibition was an issue for the aminoindane series, but this was not observed with the phenylpyrrolidine motif, which produced candidate quality molecules with potential for once-daily oral dosing in humans. (C) 2011 Elsevier Ltd. All rights reserved.