title: Synthesis and evaluation of novel ligands for the histamine H₄ receptor based on a pyrrolo[2,3-d]pyrimidine scaffold.
abstract: Starting from a known H(4)R ligand based on a pyrimidine skeleton, a series of novel analogues based on a pyrrolo[2,3-d]pyrimidine scaffold have been prepared. Whereas the original pyrimidine congener shows good affinity at hH(4)R (K(i)=0.5 μM), its lacks selectivity with a K(i) value for the hH(3)R of 1 μM. Within the newly synthesized pyrrolo[2,3-d]pyrimidines, several congeners show K(i) values of less than 1 μM at the hH(4)R and show a much improved selectivity profile. Therefore, these series represent an interesting starting point for the discovery of novel hH(4)R ligands.
authors.affiliation: KU Leuven, Rega Institute for Medical Research, Laboratory of Medicinal Chemistry, Minderbroedersstraat 10, 3000 Leuven, Belgium.
authors.forename: Ling-Jie
authors.initials: LJ
authors.lastname: Gao
authors.forename: J Stephan
authors.initials: JS
authors.lastname: Schwed
authors.forename: Lilia
authors.initials: L
authors.lastname: Weizel
authors.forename: Steven
authors.initials: S
authors.lastname: De Jonghe
authors.forename: Holger
authors.initials: H
authors.lastname: Stark
authors.forename: Piet
authors.initials: P
authors.lastname: Herdewijn
mesh_terms: D006801:Humans; D008024:Ligands; D011485:Protein Binding; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000378:metabolism*; D011968:Receptors, Histamine / Q000737:chemistry / Q000378:metabolism*; D000074040:Receptors, Histamine H4; D013329:Structure-Activity Relationship
chemical_list: C418607:HRH4 protein, human; D008024:Ligands; D011743:Pyrimidines; D011758:Pyrroles; C450639:Pyrrolo(2,3-d)pyrimidine; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4