1021179-79-2Relevant academic research and scientific papers
Fragment based design of new H4 receptor-ligands with anti-inflammatory properties in vivo
Smits, Rogier A.,Lim, Herman D.,Hanzer, Agnes,Zuiderveld, Obbe P.,Guaita, Elena,Adami, Maristella,Coruzzi, Gabriella,Leurs, Rob,De Esch, Iwan J. P.
, p. 2457 - 2467 (2008)
Using a previously reported flexible alignment model we have designed, synthesized, and evaluated a series of compounds at the human histamine H 4 receptor (H4R) from which 2-(4-methyl-piperazin-l-yl)- quinoxaline (3) was identified as a new lead structure for H4R ligands. Exploration of the structure-activity relationship (SAR) of this scaffold led to the identification of 6,7-dichloro 3-(4-methylpiperazin-l-yl) quinoxalin-2(1H)-one (VUF 10214, 57) and 2-benzyl-3-(4-methyl-piperazin-l-yl) quinoxaline (VUF 10148, 20) as potent H4R 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.
