Design, synthesis, and activity of a novel series of factor xa inhibitors: optimization of arylamidine groups(1,2).

Phillips G; Guilford WJ; Buckman BO; Davey DD; Eagen KA; Koovakkat S; Liang A; McCarrick M; Mohan R; Ng HP; Pinkerton M; Subramanyam B; Ho E; Trinh L; Whitlow M; Wu S; Xu W; Morrissey MM

首页> 外文期刊>Journal of Medicinal Chemistry >Design, synthesis, and activity of a novel series of factor xa inhibitors: optimization of arylamidine groups(1,2).

【24h】

Design, synthesis, and activity of a novel series of factor xa inhibitors: optimization of arylamidine groups(1,2).

机译：设计，合成和一系列新型的因子xa抑制剂的活性：优化芳酰胺基（1,2）。

获取原文

获取原文并翻译 | 示例

掌桥外文数据库（机构版） >>

开具论文收录证明 >>

文献代查 >>

页面导航

摘要
著录项
相似文献
相关主题

摘要

A novel series of diaryloxypyridines have been designed as selective nanomolar factor Xa (fXa) inhibitors for use as anticoagulants. In this paper, we describe our efforts to identify an additional interaction and a replacement for the distal amidine group that binds in the S3/S4 pocket of fXa. Introduction of a hydroxyl group para to the proximal amidine group increases the potency vs fXa by 1-2 orders of magnitude, which is the result of a hydrogen bond to Ser195 of the catalytic triad. A methyl imidazoline and a dimethylamide are good alternatives for the second amidine. These substitutions have increased the selectivity vs the related serine proteases trypsin and thrombin. The synthesis, in vitro activity, and hypothetical modes of binding to fXa based on trypsin crystallographic data are outlined.

机译：已经设计了一系列新颖的二芳基氧基吡啶作为用作抗凝剂的选择性纳摩尔因子Xa（fXa）抑制剂。在本文中，我们描述了我们的工作，以确定与fXa的S3 / S4口袋结合的远端am基团的其他相互作用和替代物。在近端am基团对位引入羟基可使相对于fXa的效价提高1-2个数量级，这是氢与催化三联体的Ser195键合的结果。甲基咪唑啉和二甲基酰胺是第二种idine的良好替代品。与相关的丝氨酸蛋白酶胰蛋白酶和凝血酶相比，这些取代提高了选择性。概述了基于胰蛋白酶晶体学数据的合成，体外活性和与fXa结合的假设模式。

著录项

来源
《Journal of Medicinal Chemistry》 |2002年第12期|共10页
作者
Phillips G; Guilford WJ; Buckman BO; Davey DD; Eagen KA; Koovakkat S; Liang A; McCarrick M; Mohan R; Ng HP; Pinkerton M; Subramanyam B; Ho E; Trinh L; Whitlow M; Wu S; Xu W; Morrissey MM;
展开▼
作者单位

展开▼
收录信息
原文格式 PDF
正文语种 eng
中图分类药学;
关键词
novel; inhibitors; Amidines; Trypsin; hydroxyl group; 脒类; 胰蛋白酶;

机译：novel;inhibitors;Amidines;Trypsin;hydroxyl group;脒类;胰蛋白酶;

相似文献

外文文献
中文文献
专利

1. Design, synthesis, and activity of a novel series of factor xa inhibitors: optimization of arylamidine groups(1,2). [J] . Phillips G, Guilford WJ, Buckman BO, Journal of Medicinal Chemistry . 2002,第12期

机译：设计，合成和一系列新型的因子xa抑制剂的活性：优化芳酰胺基（1,2）。
2. Design, synthesis and structure-activity relationship of a series of arginine aldehyde factor Xa inhibitors. Part 1: structures based on the (D)-Arg-Gly-Arg tripeptide sequence. [J] . Marlowe CK, Sinha U, Gunn AC, Bioorganic and Medicinal Chemistry Letters . 2000,第1期

机译：一系列精氨酸醛因子Xa抑制剂的设计，合成及构效关系第1部分：基于（D）-Arg-Gly-Arg三肽序列的结构。
3. Synthesis and Evaluation of 1-ArylsuIfonyl-3-piperazinone Derivatives as Factor Xa Inhibitors~(1-4))V.A Series of New Derivatives Containing a Spiro[imidazo[1,2-a]pyrazine-2(3H),4'-piperidin]-5(1H)-one Scaffold [J] . Fumihiko SAITOH, Takafumi MUKAIHIRA, Hidemitsu NISHIDA Chemical and Pharmaceutical Bulletin . 2006,第11期

机译：1-芳基磺酰基-3-哌嗪酮衍生物作为Xa因子抑制剂的合成和评价〜（1-4））VA系列含螺并[咪唑并[1,2-a]吡嗪-2（3H），4'-的新衍生物哌啶] -5（1H）-一种支架
4. Synthesis a novel inhibitor of factor Xa [C] . Shen An Xiong, Yang Gen Sheng 2011 International Conference on Remote Sensing, Environment and Transportation Engineering . 2011

机译：合成Xa因子抑制剂
5. Part I. Isolation of natural product inhibitors and synthesis of inhibitors of signal transduction. Part II. Structure-activity relationship for a series of glycosidase inhibitors. [D] . Fraser, Rebecca Dawn. 1993

机译：第一部分：天然产物抑制剂的分离和信号转导抑制剂的合成。第二部分一系列糖苷酶抑制剂的构效关系。
6. Innovative Three-Step Microwave-Promoted Synthesis of N-Propargyltetrahydroquinoline and 123-Triazole Derivatives as a Potential Factor Xa (FXa) Inhibitors: Drug Design Synthesis and Biological Evaluation [O] . Fabián Santana-Romo, Carlos F. Lagos, Yorley Duarte, 2020

机译：创新的三步微波促进合成N-炔丙基四氢喹啉和123-三唑衍生物作为潜在因子Xa（FXa）抑制剂：药物设计合成和生物学评估
7. Design, Synthesis and Biological Activity of Potent and Selective Inhibitors of Blood Coagulation Factor Xa [O] . -1

机译：血液凝固因子Xa效力和选择性抑制剂的设计，合成和生物活性

Design, synthesis, and activity of a novel series of factor xa inhibitors: optimization of arylamidine groups(1,2).

摘要

著录项

相似文献

相关主题

期刊订阅