| Focused Library Sets in Discovery of Dual AT1/ETA Antagonists |
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Presentation: P01007 Session: Cheminformatics, Library Design and Virtual HTS - Poster SessionHenrik Konarkowski and Alexander S. Kiselyov, ChemDiv, Inc. Presenting Author: Henrik Konarkowski, ChemDiv, Inc. - USA At ChemDiv, we have assembled a set of biased compound libraries designed to jump-start medicinal chemistry efforts around specific targets or pathways. In this presentation, we will comment on our success in utilizing several of these targeted selections, namely kinase-, GPCR-, recognition motif- and Rule-of-Three sets in identifying potent ETA and AT1 hits. This initial insight allowed us to successfully complete medicinal chemistry effort that yielded three new chemical series of dual AT1/ETA antagonists with Ki < 250 nM against both receptors, good cellular activity, as well as in vitro PK and early in vivo profiles. In addition, identified compounds were selective against panel of 35 additional GPCRs and show no significant binding in CYP450 panel and hERG1 assay. |