1-ethyl-2-(hydroxymethyl)indole-6-carbonitrile | 200184-03-8

• 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-ethyl-2-(hydroxymethyl)indole-6-carbonitrile
• CAS: 200184-03-8
• 化学式: C₁₂H₁₂N₂O
• 分子量: 200.24
• InChiKey: BKTDPNAVSAPZHF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  49
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-ethyl-2-(hydroxymethyl)indole-6-carbonitrile 在 palladium(II) oxide 、 barium sulfate 盐酸 、 乙醇 、 氢气 、 三溴化磷 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 52.0h， 生成 3-(6-Carbamimidoyl-1-ethyl-1H-indol-2-yl)-2-[4-((S)-pyrrolidin-3-yloxy)-phenyl]-propionic acid ethyl ester
  参考文献：
  名称：

  Design, synthesis and biological activity of amidinobicyclic compounds (derivatives of DX-9065a) as factor Xa inhibitors: SAR study of S1 and aryl binding sites

  摘要：

  Since factor Xa (fXa) plays a pivotal role in the blood coagulation cascade, inhibition of fXa is thought to be an effective treatment for a variety of thrombotic events. (2,)-2-[4-[[(3S)-l-Acetimidoyl-3-pyrrolidinyl]oxy]phenyl]-3-(7-amidino-2-naphthyl)propanoic acid hydrochloride pentahydrate (DX-9065a) was previously found in our laboratory as a novel orally active factor Xa inhibitor. DX-9065a exhibits a strong inhibitory activity toward fXa by occupying the substrate recognition (called SI) sites and aryl binding sites of fXa. Herein we describe conversions of the amidinonaphthalene and the acetimidoylpyrrolidine moieties of DX-9065a. Some compounds showed remarkably increased in vitro anti-factor Xa and PRCT activities compared with those of DX9065a. The most promising compound 38 showed four times the prolongation of APTT against DX-9065a after oral administration to rats. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.02.032
• 作为产物：
  描述：

  6-氰基吲哚-2-甲酸乙酯 在 sodium tetrahydroborate 、 碳酸氢钠 、 caesium carbonate 、 calcium iodide 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 1-ethyl-2-(hydroxymethyl)indole-6-carbonitrile
  参考文献：
  名称：

  Design, synthesis and structure–Activity relationships of benzoxazinone-Based factor Xa inhibitors

  摘要：

  A series of benzoxazinone derivatives was designed and synthesized as factor Xa inhibitors. We demonstrated that the naphthyl moiety in the aniline-based compounds I and 2 can be replaced with benzene-fused heterobicycles and biaryls to give factor Xa inhibitors with improved trypsin selectivity. The P4 modifications lead to monoamidines which are moderately active. The benzoxazinones 41-45 are potent against factor Xa, retain the improved trypsin selectivity of the corresponding aniline-based compounds, and show strong antithrombotic effect dose responsively. (C) 2002 Published by Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(02)00927-7

文献信息

• Aromatic amidine derivatives useful as selective thrombin inhibitors
  申请人：C & C Research Laboratories

  公开号：US06201006B1

  公开（公告）日：2001-03-13

  The present invention relates to a novel thrombin inhibitor which is effective even when orally administered. More specifically, the present invention relates to an aromatic amidine derivative represented by formula (I) and the salts thereof, which show potent selective inhibitory activity for thrombin in which (a), R, R1, R2, R3, A, W, Y and n are defined as described in the specification.

  本发明涉及一种新颖的凝血酶抑制剂，即使口服给药也有效。更具体地说，本发明涉及一种由公式（I）表示的芳香族酰胺衍生物及其盐，其对凝血酶具有强的选择性抑制活性，其中（a），R，R1，R2，R3，A，W，Y和n如说明书所述定义。
• [EN] AROMATIC AMIDINE DERIVATIVES USEFUL AS SELECTIVE THROMBIN INHIBITORS<br/>[FR] DERIVES D'AMIDINE AROMATIQUE UTILES EN TANT QU'INHIBITEURS SELECTIFS DE LA THROMBINE
  申请人：C & C RESEARCH LABORATORIES

  公开号：WO1997045424A1

  公开（公告）日：1997-12-04

  (EN) The present invention relates to a novel thrombin inhibitor which is effective even when orally administered. More specifically, the present invention relates to an aromatic amidine derivative represented by formula (I) and the salts thereof, which show potent selective inhibitory activity for thrombin in which (a), R, R1, R2, R3, A, W, Y and n are defined as described in the specification.(FR) L'invention concerne un nouvel inhibiteur de la thrombine qui est efficace même lorsqu'il est administré par voie orale. Plus spécifiquement, l'invention concerne un dérivé d'amidine aromatique représenté par la formule (I) et des sels de celle-ci, qui présentent une activité inhibitrice sélective pour la thrombine. Dans ladite formule, (a), R, R1, R2, R3 A, W, Y et n sont définis comme décrits dans la spécification.

  本发明涉及一种新型的抑制凝血酶的药物，即使口服也具有有效性。更具体地说，本发明涉及一种芳香基脒衍生物及其盐，其在(a)、R、R1、R2、R3、A、W、Y和n如规范所述的情况下，对凝血酶具有强有力的选择性抑制活性。
• AROMATIC AMIDINE DERIVATIVES USEFUL AS SELECTIVE THROMBIN INHIBITORS
  申请人：C & C Research Laboratories

  公开号：EP0918768A1

  公开（公告）日：1999-06-02
• US6201006B1
  申请人：——

  公开号：US6201006B1

  公开（公告）日：2001-03-13
• Design, synthesis and structure–Activity relationships of benzoxazinone-Based factor Xa inhibitors
  作者：Wenrong Huang、Penglie Zhang、Jingmei F Zuckett、Lingyan Wang、John Woolfrey、Yonghong Song、Zhaozhong J Jia、Lane A Clizbe、Ting Su、Katherine Tran、Brian Huang、Paul Wong、Uma Sinha、Gary Park、Andrea Reed、John Malinowski、Stanley J Hollenbach、Robert M Scarborough、Bing-Yan Zhu

  DOI：10.1016/s0960-894x(02)00927-7

  日期：2003.2

  A series of benzoxazinone derivatives was designed and synthesized as factor Xa inhibitors. We demonstrated that the naphthyl moiety in the aniline-based compounds I and 2 can be replaced with benzene-fused heterobicycles and biaryls to give factor Xa inhibitors with improved trypsin selectivity. The P4 modifications lead to monoamidines which are moderately active. The benzoxazinones 41-45 are potent against factor Xa, retain the improved trypsin selectivity of the corresponding aniline-based compounds, and show strong antithrombotic effect dose responsively. (C) 2002 Published by Elsevier Science Ltd.