1-(3-amino-1,2-benzisoxazol-5-yl)-5-{[5-(2-oxo-1(2H)-pyridinyl)-2,3-dihydro-1H-indol-1-yl]carbonyl}-1H-pyrazole-3-carboxamide

• 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-(3-amino-1,2-benzisoxazol-5-yl)-5-{[5-(2-oxo-1(2H)-pyridinyl)-2,3-dihydro-1H-indol-1-yl]carbonyl}-1H-pyrazole-3-carboxamide
• 英文别名: 1-(3-aminobenzo[d]isoxazol-5-yl)-5-(5-(2-oxopyridin-1(2H)-yl)indoline-1-carbonyl)-1H-pyrazole-3-carboxamide；1-(3-amino-1,2-benzoxazol-5-yl)-5-[5-(2-oxopyridin-1-yl)-2,3-dihydroindole-1-carbonyl]pyrazole-3-carboxamide
• 化学式: C₂₅H₁₉N₇O₄
• 分子量: 481.47
• InChiKey: UQHLDZFSQPJXIW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  36
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  154
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  5-碘吲哚 在 吡啶 、 copper(l) iodide 、 sodium cyanoborohydride 、 potassium carbonate 、 溶剂黄146 、 三氟乙酸 、 N,N'-二异丙基碳二亚胺 作用下， 以 二氯甲烷 、 水 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 66.83h， 生成 1-(3-amino-1,2-benzisoxazol-5-yl)-5-{[5-(2-oxo-1(2H)-pyridinyl)-2,3-dihydro-1H-indol-1-yl]carbonyl}-1H-pyrazole-3-carboxamide
  参考文献：
  名称：

  LACTAM-CONTAINING COMPOUNDS AND DERIVATIVES THEREOF AS FACTOR XA INHIBITORS

  摘要：

  本申请描述了公式I中含有内酰胺的化合物及其衍生物：P4—P-M-M4I或其药用盐形式，其中环P（如果存在）是一个5-7成员的碳环或杂环，环M是一个5-7成员的碳环或杂环。本发明的化合物可用作胰蛋白酶样丝氨酸蛋白酶的抑制剂，特别是因子Xa。

  公开号：

  US20170050964A1

文献信息

• Lactam-containing compounds and derivatives thereof as factor Xa inhibitors
  申请人：——

  公开号：US20030191115A1

  公开（公告）日：2003-10-09

  The present application describes lactam-containing compounds and derivatives thereof of Formula I: 1 or pharmaceutically acceptable salt forms thereof, wherein ring P, if present is a 5-7 membered carbocycle or heterocycle and ring M is a 5-7 membered carbocycle or heterocycle. Compounds of the present invention are useful as inhibitors of trypsin-like serine proteases, specifically factor Xa.

  本申请描述了具有Formula I的内酰胺含有化合物及其衍生物，或其药用可接受的盐形式，其中环P（如存在）是一个5-7成员碳环或杂环，环M是一个5-7成员碳环或杂环。本发明的化合物可用作胰蛋白酶样丝氨酸蛋白酶的抑制剂，特别是因子Xa。
• Lactam-containing compounds and derivatives thereof as factor xa inhibitors
  申请人：Pinto J.P. Donald

  公开号：US20050267097A1

  公开（公告）日：2005-12-01

  The present application describes lactam-containing compounds and derivatives thereof of Formula I: P 4 —P-M-M 4 I or pharmaceutically acceptable salt forms thereof, wherein ring P, if present is a 5-7 membered carbocycle or heterocycle and ring M is a 5-7 membered carbocycle or heterocycle. Compounds of the present invention are useful as inhibitors of trypsin-like serine proteases, specifically factor Xa.

  本申请描述了公式I中含有内酰胺化合物及其衍生物，或其药学上可接受的盐形式，其中环P（如存在）是一个5-7成员的碳环或杂环，环M是一个5-7成员的碳环或杂环。本发明的化合物可用作胰蛋白酶样丝氨酸蛋白酶的抑制剂，特别是因子Xa的抑制剂。
• Lactam-containing compounds and derivatives thereof as factor XA inhibitors
  申请人：Bristol-Myers Squibb Company

  公开号：EP2105436A1

  公开（公告）日：2009-09-30

  The present application describes lactam-containing compounds and derivatives thereof of Formula I: P4-P-M-M-4 or pharmaceutically acceptable salt forms thereof, wherein ring P, if present is a 5-7 membered carbocycle or heterocycle and ring M is a 5-7 membered carbocycle or heterocycle. Compounds of the present invention are useful as inhibitors of trypsin-like serine proteases, specifically factor Xa.

  本申请描述了式 I 的含内酰胺化合物及其衍生物：P4-P-M-M-4或其药学上可接受的盐形式，其中环P（如果存在）是5-7个成员的碳环或杂环，环M是5-7个成员的碳环或杂环。本发明的化合物可用作胰蛋白酶样丝氨酸蛋白酶，特别是 Xa 因子的抑制剂。
• Design, structure–activity relationship, and pharmacokinetic profile of pyrazole-based indoline factor Xa inhibitors
  作者：Jeffrey G. Varnes、Dean A. Wacker、Irina C. Jacobson、Mimi L. Quan、Christopher D. Ellis、Karen A. Rossi、Ming Y. He、Joseph M. Luettgen、Robert M. Knabb、Steven Bai、Kan He、Patrick Y.S. Lam、Ruth R. Wexler

  DOI：10.1016/j.bmcl.2007.09.091

  日期：2007.12

  A new series of pyrazole-based factor Xa inhibitors have been identified as part of our ongoing efforts to optimize previously reported clinical candidate razaxaban. Concern over the possible formation of primary aniline metabolites via amide hydrolysis led to the replacement of the primary amide linker between the pyrazole and phenyl moieties with secondary amides. This was accomplished by replacing the aniline with a variety of heterobicycles, of which indolines were the most potent. The indoline series demonstrated subnanomolar factor Xa binding K(i)s, modest to high selectivity versus other serine proteases, and good in vitro clotting activity. A small number of indoline fXa inhibitors were pro. led in a dog pharmacokinetic model, one of which demonstrated pharmacokinetic parameters similar to that of clinical candidate razaxaban. (c) 2007 Elsevier Ltd. All rights reserved.
• US6967208B2
  申请人：——

  公开号：US6967208B2

  公开（公告）日：2005-11-22