• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

新型凝血因子Xa抑制剂的设计、合成及生物活性：通过S1和S4配体修饰提高代谢稳定性

Design, synthesis, and biological activity of novel factor Xa inhibitors: improving metabolic stability by S1 and S4 ligand modification.

作者信息

Komoriya Satoshi, Kobayashi Shozo, Osanai Ken, Yoshino Toshiharu, Nagata Tsutomu, Haginoya Noriyasu, Nakamoto Yumi, Mochizuki Akiyoshi, Nagahara Takayasu, Suzuki Makoto, Shimada Takashi, Watanabe Kengo, Isobe Yumiko, Furugoori Taketoshi

机构信息

Tokyo R&D Center, Daiichi Pharmaceutical Co. Ltd, Edogawa-ku, Japan.

出版信息

Bioorg Med Chem. 2006 Mar 1;14(5):1309-30. doi: 10.1016/j.bmc.2005.09.056. Epub 2005 Nov 2.

DOI:10.1016/j.bmc.2005.09.056
PMID:16263291
Abstract

Serine protease factor xa (fXa) inhibitor 1 showed good ex vivo anti-fXa activity upon oral administration in rats. However, it has been revealed that 1 had low metabolic stability against human liver microsomes. To improve the metabolic stability, we attempted to modify the S1 and S4 ligands of 1. These modifications resulted in compound 34b, which exhibited selective anti-fXa activity and excellent anti-coagulation activity.

摘要

丝氨酸蛋白酶因子Xa（fXa）抑制剂1在大鼠口服给药后显示出良好的体外抗fXa活性。然而，已发现1对人肝微粒体的代谢稳定性较低。为了提高代谢稳定性，我们尝试修饰1的S1和S4配体。这些修饰产生了化合物34b，其表现出选择性抗fXa活性和优异的抗凝血活性。

相似文献

1
Design, synthesis, and biological activity of novel factor Xa inhibitors: improving metabolic stability by S1 and S4 ligand modification.新型凝血因子Xa抑制剂的设计、合成及生物活性：通过S1和S4配体修饰提高代谢稳定性
Bioorg Med Chem. 2006 Mar 1;14(5):1309-30. doi: 10.1016/j.bmc.2005.09.056. Epub 2005 Nov 2.
2
Design, synthesis, and biological activity of non-basic compounds as factor Xa inhibitors: SAR study of S1 and aryl binding sites.非碱性化合物作为凝血因子Xa抑制剂的设计、合成及生物活性：S1和芳基结合位点的构效关系研究
Bioorg Med Chem. 2005 Jun 2;13(12):3927-54. doi: 10.1016/j.bmc.2005.04.006.
3
Orally active factor Xa inhibitor: synthesis and biological activity of masked amidines as prodrugs of novel 1,4-diazepane derivatives.
Bioorg Med Chem. 2004 Oct 15;12(20):5415-26. doi: 10.1016/j.bmc.2004.07.046.
4
Rational design and synthesis of novel, potent bis-phenylamidine carboxylate factor Xa inhibitors.新型强效双苯基脒羧酸酯因子Xa抑制剂的合理设计与合成
J Med Chem. 1998 Jan 1;41(1):53-62. doi: 10.1021/jm970485a.
5
Structure- and property-based design of factor Xa inhibitors: pyrrolidin-2-ones with acyclic alanyl amides as P4 motifs.基于结构和性质的凝血因子Xa抑制剂设计：以无环丙氨酰酰胺为P4基序的吡咯烷-2-酮类化合物
Bioorg Med Chem Lett. 2006 Dec 1;16(23):5953-7. doi: 10.1016/j.bmcl.2006.09.001. Epub 2006 Sep 18.
6
Design, synthesis, and biological evaluation of peptidomimetic inhibitors of factor XIa as novel anticoagulants.作为新型抗凝剂的凝血因子XIa拟肽抑制剂的设计、合成及生物学评价
J Med Chem. 2006 Dec 28;49(26):7781-91. doi: 10.1021/jm060978s.
7
Design and structure-activity relationships of potent and selective inhibitors of blood coagulation factor Xa.凝血因子Xa强效和选择性抑制剂的设计及其构效关系
J Med Chem. 1999 Sep 9;42(18):3557-71. doi: 10.1021/jm990040h.
8
Design, synthesis, and biological activity of potent and selective inhibitors of blood coagulation factor Xa.凝血因子Xa高效选择性抑制剂的设计、合成及生物活性
J Med Chem. 2004 Jul 29;47(16):4089-99. doi: 10.1021/jm0497491.
9
Synthesis and evaluation of acylguanidine FXa inhibitors.
Bioorg Med Chem Lett. 2008 Aug 15;18(16):4696-9. doi: 10.1016/j.bmcl.2008.07.004. Epub 2008 Jul 5.
10
Design, synthesis and biological activity of amidinobicyclic compounds (derivatives of DX-9065a) as factor Xa inhibitors: SAR study of S1 and aryl binding sites.作为凝血因子Xa抑制剂的脒基双环化合物（DX-9065a衍生物）的设计、合成及生物活性：S1和芳基结合位点的构效关系研究
Bioorg Med Chem. 2004 May 1;12(9):2099-114. doi: 10.1016/j.bmc.2004.02.032.

引用本文的文献

1
Mechanistic Insights into Biological Activities of Polyphenolic Compounds from Rosemary Obtained by Inverse Molecular Docking.通过反向分子对接获得的迷迭香多酚类化合物生物活性的机制洞察
Foods. 2021 Dec 28;11(1):67. doi: 10.3390/foods11010067.
2
A novel and expedient approach to new thiazoles, thiazolo[3,2-a]pyridines, dihydrothiophenes, and hydrazones incorporating thieno[2,3-b]thiophene moiety.一种合成含有噻吩并[2,3-b]噻吩部分的新型噻唑、噻唑并[3,2-a]吡啶、二氢噻吩和腙的新颖且便捷的方法。
Int J Mol Sci. 2012;13(4):5035-5047. doi: 10.3390/ijms13045035. Epub 2012 Apr 23.
3
A lead discovery strategy driven by a comprehensive analysis of proteases in the peptide substrate space.
基于对肽底物空间中蛋白酶的综合分析的先导发现策略。
Protein Sci. 2010 Nov;19(11):2096-109. doi: 10.1002/pro.490.