Sie befinden Sich nicht im Netzwerk der Universität Paderborn. Der Zugriff auf elektronische Ressourcen ist gegebenenfalls nur via VPN oder Shibboleth (DFN-AAI) möglich. mehr Informationen...
Detailed structure–activity relationship of indolecarboxamides as H4 receptor ligands
Ist Teil von
European journal of medicinal chemistry, 2012-08, Vol.54, p.660-668
Ort / Verlag
Kidlington: Elsevier Masson SAS
Erscheinungsjahr
2012
Link zum Volltext
Quelle
Elsevier ScienceDirect Journals Complete
Beschreibungen/Notizen
A series of 76 derivatives of the indolecarboxamide 1 were synthesized, which allows a detailed SAR investigation of this well known scaffold. The data enable the definition of a predictive QSAR model which identifies several compounds with an activity comparable to 1. A selection of these new H4R antagonists was synthesized and a comparison of predicted and measured values demonstrates the robustness of the model (47–55). In addition to the H4-receptor activity general CMC and DMPK properties were investigated. Some of the new analogs are not only excellently soluble, but display a significantly increased half-life in mouse liver microsomes as well. These properties qualify these compounds as a possible new standard for future in vivo studies (e.g 51, 52 and 55). Moreover, the current studies also provide valuable information on the potential receptor ligand interactions between the indolcarboxamides and the H4R protein.
[Display omitted]
► Comprehensive SAR for H4R affinity around the indolecarboxamide scaffold. ► Predictive Free-Wilson QSAR model established. ► Identification of microsomal stable indolecarboxamide derivatives.