Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10587348 | Bioorganic & Medicinal Chemistry Letters | 2013 | 6 Pages |
Abstract
The structural diversity and SAR in a series of imidazopyridazine inhibitors of Plasmodium falciparum calcium dependent protein kinase 1 (PfCDPK1) has been explored and extended. The opportunity to further improve key ADME parameters by means of lowering log D was identified, and this was achieved by replacement of a six-membered (hetero)aromatic linker with a pyrazole. A short SAR study has delivered key examples with useful in vitro activity and ADME profiles, good selectivity against a human kinase panel and improved levels of lipophilic ligand efficiency. These new analogues thus provide a credible additional route to further development of the series.
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Authors
Jonathan M. Large, Simon A. Osborne, Ela Smiljanic-Hurley, Keith H. Ansell, Hayley M. Jones, Debra L. Taylor, Barbara Clough, Judith L. Green, Anthony A. Holder,