Fragment Based Design of New H4Receptor−Ligands with Anti-inflammatory Properties in Vivo
Journal of Medicinal Chemistry2008Vol. 51(8), pp. 2457–2467
Citations Over TimeTop 10% of 2008 papers
Rogier A. Smits, Herman D. Lim, Agnes Hanzer, Obbe P. Zuiderveld, Elena Guaita, Maristella Adami, Gabriella Coruzzi, Rob Leurs, Iwan J. P. de Esch
Abstract
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.
Related Papers
- → Comparison of an in vitro method and an in vivo method of Giardia excystation(1992)23 cited
- → IN VITRO SPECIFICITY AND IN VIVO ACTIVITY OF ANTIMACROPHAGE SERUM(1974)4 cited
- → Actin Organization as an in Vitro Assay for Tumorigenicity(1982)2 cited
- [Pharmacodynamic study of the in vitro clonogenic assay--with reference to dose levels].(1988)
- The release of the marked insulin J125 from ointment in vitro and in vivo.(1993)