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Fragment based design of new H4 receptor-ligands with anti-inflammatory properties in vivo.
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2008 Apr 24 , DOI: 10.1021/jm7014217 Rogier A. Smits 1 , Herman D. Lim 1 , Agnes Hanzer 1 , Obbe P. Zuiderveld 1 , Elena Guaita 1 , Maristella Adami 1 , Gabriella Coruzzi 1 , Rob Leurs 1 , Iwan J. P. de Esch 1
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2008 Apr 24 , DOI: 10.1021/jm7014217 Rogier A. Smits 1 , Herman D. Lim 1 , Agnes Hanzer 1 , Obbe P. Zuiderveld 1 , Elena Guaita 1 , Maristella Adami 1 , Gabriella Coruzzi 1 , Rob Leurs 1 , Iwan J. P. de Esch 1
Affiliation
Using a previously reported flexible alignment model we have designed, synthesized, and evaluated a series of compounds at the human histamine H 4 receptor (H 4R) from which 2-(4-methyl-piperazin-1-yl)-quinoxaline ( 3) was identified as a new lead structure for H 4R ligands. Exploration of the structure-activity relationship (SAR) of this scaffold led to the identification of 6,7-dichloro 3-(4-methylpiperazin-1-yl)quinoxalin-2(1 H)-one (VUF 10214, 57) and 2-benzyl-3-(4-methyl-piperazin-1-yl)quinoxaline (VUF 10148, 20) as potent H 4R ligands with nanomolar affinities. In vivo studies in the rat reveal that compound 57 has significant anti-inflammatory properties in the carrageenan-induced paw-edema model.
中文翻译:
基于片段的新型H4受体配体在体内具有抗炎特性。
使用先前报告的灵活比对模型,我们已经设计,合成和评估了人类组胺H 4受体(H 4R)上的一系列化合物,其中2-(4-甲基-哌嗪-1-基)-喹喔啉(3)被鉴定为H 4R配体的新的先导结构。探索该支架的构效关系(SAR)导致鉴定出6,7-二氯3-(4-甲基哌嗪-1-基)喹喔啉-2(1 H)-一(VUF 10214,57)和2-苄基-3-(4-甲基-哌嗪-1-基)喹喔啉(VUF 10148,20)作为具有纳摩尔亲和力的强效H 4R配体。在大鼠体内的研究表明,化合物57在角叉菜胶诱导的爪水肿模型中具有显着的抗炎特性。
更新日期:2017-01-31
中文翻译:
![](https://scdn.x-mol.com/jcss/images/paperTranslation.png)
基于片段的新型H4受体配体在体内具有抗炎特性。
使用先前报告的灵活比对模型,我们已经设计,合成和评估了人类组胺H 4受体(H 4R)上的一系列化合物,其中2-(4-甲基-哌嗪-1-基)-喹喔啉(3)被鉴定为H 4R配体的新的先导结构。探索该支架的构效关系(SAR)导致鉴定出6,7-二氯3-(4-甲基哌嗪-1-基)喹喔啉-2(1 H)-一(VUF 10214,57)和2-苄基-3-(4-甲基-哌嗪-1-基)喹喔啉(VUF 10148,20)作为具有纳摩尔亲和力的强效H 4R配体。在大鼠体内的研究表明,化合物57在角叉菜胶诱导的爪水肿模型中具有显着的抗炎特性。