Potent bicyclic inhibitors of malarial cGMP-dependent protein kinase: approaches to combining improvements in cell potency,selectivity and structural novelty |
| |
| Institution: | 1. Centre for Therapeutics Discovery, LifeArc, Accelerator Building, Open Innovation Campus, Stevenage SG1 2FX, UK;2. Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, Keppel Street, London WC1E 7HT, UK |
| |
| Abstract: | Focussed studies on imidazopyridine inhibitors of Plasmodium falciparum cyclic GMP-dependent protein kinase (PfPKG) have significantly advanced the series towards desirable in vitro property space. LLE-based approaches towards combining improvements in cell potency, key physicochemical parameters and structural novelty are described, and a structure-based design hypothesis relating to substituent regiochemistry has directed efforts towards key examples with well-balanced potency, ADME and kinase selectivity profiles. |
| |
| Keywords: | Malaria cGMP Protein kinase G Imidazopyridine SAR |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
