2-{4-[2-(5-chloro-thiophen-2-yl)-ethenesulfonyl]-2-oxopiperazin-1-ylmethyl}-pyrrolo[2,3-c]pyridine-1-carboxylic acid tert-butyl ester | 502768-13-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2-{4-[2-(5-chloro-thiophen-2-yl)-ethenesulfonyl]-2-oxopiperazin-1-ylmethyl}-pyrrolo[2,3-c]pyridine-1-carboxylic acid tert-butyl ester
• 英文别名: tert-butyl 2-[[4-[(E)-2-(5-chlorothiophen-2-yl)ethenyl]sulfonyl-2-oxopiperazin-1-yl]methyl]pyrrolo[3,2-c]pyridine-1-carboxylate
• CAS: 502768-13-0
• 化学式: C₂₃H₂₅ClN₄O₅S₂
• 分子量: 537.06
• InChiKey: DHCQLJAFPRBWEK-YRNVUSSQSA-N

物化性质

• 沸点：
  746.7±70.0 °C(predicted)
• 密度：
  1.43±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  138
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-{4-[2-(5-chloro-thiophen-2-yl)-ethenesulfonyl]-2-oxopiperazin-1-ylmethyl}-pyrrolo[2,3-c]pyridine-1-carboxylic acid tert-butyl ester 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 5.5h， 以1.29 g的产率得到RPR 209685
  参考文献：
  名称：

  Discovery of an Orally Efficacious Inhibitor of Coagulation Factor Xa Which Incorporates a Neutral P₁ Ligand

  摘要：

  The discovery and SAR of ketopiperazino methylazaindole factor Xa inhibitors are described. Structureactivity data suggesting that this class of inhibitors does not bind in the canonical mode were confirmed by an X-ray crystal structure showing the neutral haloaromatic bound in the S, subsite. The most potent azaindole, 33 (RPR209685), is selective against related serine proteases and attains higher levels of exposure upon oral dosing than comparable benzamidines and benzamidine isosteres. Compound 33 was efficacious in the canine AV model of thrombosis.

  DOI：

  10.1021/jm020384z
• 作为产物：
  描述：

  4-氨基-3-碘吡啶 在 钯 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 甲酸 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 6.67h， 生成 2-{4-[2-(5-chloro-thiophen-2-yl)-ethenesulfonyl]-2-oxopiperazin-1-ylmethyl}-pyrrolo[2,3-c]pyridine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Discovery of an Orally Efficacious Inhibitor of Coagulation Factor Xa Which Incorporates a Neutral P₁ Ligand

  摘要：

  The discovery and SAR of ketopiperazino methylazaindole factor Xa inhibitors are described. Structureactivity data suggesting that this class of inhibitors does not bind in the canonical mode were confirmed by an X-ray crystal structure showing the neutral haloaromatic bound in the S, subsite. The most potent azaindole, 33 (RPR209685), is selective against related serine proteases and attains higher levels of exposure upon oral dosing than comparable benzamidines and benzamidine isosteres. Compound 33 was efficacious in the canine AV model of thrombosis.

  DOI：

  10.1021/jm020384z

文献信息

• Substituted oxoazaheterocyclyl compounds
  申请人：AVENTIS PHARMACEUTICALS INC.

  公开号：US20040102450A1

  公开（公告）日：2004-05-27

  This invention is directed to oxoazaheterocycyl compounds which inhibit Factor Xa, to oxoazaheterocycyl compounds which inhibit both Factor Xa and Factor IIa, to pharmaceutical compositions comprising these compounds, to intermediates useful for preparing these compounds, to a method of directly inhibiting Factor Xa and to a method of simultaneously directly inhibiting Factor Xa and Factor IIa..

  这项发明涉及抑制因子Xa的氧杂杂环化合物，抑制同时抑制因子Xa和因子IIa的氧杂杂环化合物，包含这些化合物的药物组合物，用于制备这些化合物的中间体，直接抑制因子Xa的方法，以及同时直接抑制因子Xa和因子IIa的方法。
• SUBSTITUTED OXOAZAHETEROCYCLYL COMPOUNDS
  申请人：Aventis Pharmaceuticals Inc.

  公开号：EP1208097A2

  公开（公告）日：2002-05-29
• US7612075B2
  申请人：——

  公开号：US7612075B2

  公开（公告）日：2009-11-03
• [EN] SUBSTITUTED OXOAZAHETEROCYCLYL COMPOUNDS<br/>[FR] COMPOSES D'OXOAZAHETEROCYCLYLE SUBSTITUE
  申请人：AVENTIS PHARM PROD INC

  公开号：WO2001007436A2

  公开（公告）日：2001-02-01

  This invention is directed to oxoazaheterocyclyl compounds which inhibit Factor Xa, to oxoazaheterocyclyl compounds which inhibit both Factor Xa and Factor IIa, to pharmaceutical compositions comprising these compounds, to intermediates useful for preparing these compounds, to a method of directly inhibiting Factor Xa and to a method of simultaneously directly inhibiting Factor Xa and Factor IIa.
• Discovery of an Orally Efficacious Inhibitor of Coagulation Factor Xa Which Incorporates a Neutral P₁ Ligand
  作者：Yong Mi Choi-Sledeski、Robert Kearney、Gregory Poli、Henry Pauls、Charles Gardner、Yong Gong、Michael Becker、Roderick Davis、Alfred Spada、Guyan Liang、Valeria Chu、Karen Brown、Dennis Collussi、Robert Leadley,、Sam Rebello、Phillip Moxey、Suzanne Morgan、Ross Bentley、Charles Kasiewski、Sebastien Maignan、Jean-Pierre Guilloteau、Vincent Mikol

  DOI：10.1021/jm020384z

  日期：2003.2.1

  The discovery and SAR of ketopiperazino methylazaindole factor Xa inhibitors are described. Structureactivity data suggesting that this class of inhibitors does not bind in the canonical mode were confirmed by an X-ray crystal structure showing the neutral haloaromatic bound in the S, subsite. The most potent azaindole, 33 (RPR209685), is selective against related serine proteases and attains higher levels of exposure upon oral dosing than comparable benzamidines and benzamidine isosteres. Compound 33 was efficacious in the canine AV model of thrombosis.