1. Design, synthesis, and structure-activity-relationship of phenyl imidazoles as potent Smoothened antagonists
- Author
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Shifeng Pan, Wenqi Gao, Nathan P. Englund, Tove Tuntland, Dai Cheng, Xu Wu, Yongqin Wan, Jiqing Jiang, Dong Han, and Qihui Jing
- Subjects
Stereochemistry ,Clinical Biochemistry ,Pharmaceutical Science ,Administration, Oral ,Antineoplastic Agents ,Biochemistry ,Receptors, G-Protein-Coupled ,chemistry.chemical_compound ,Inhibitory Concentration 50 ,Mice ,Structure-Activity Relationship ,In vivo ,Drug Discovery ,Structure–activity relationship ,Inhibitory concentration 50 ,Imidazole ,Animals ,Humans ,Molecular Biology ,Chemistry ,Organic Chemistry ,Antagonist ,Imidazoles ,Combinatorial chemistry ,Smoothened Receptor ,Rats ,Design synthesis ,Area Under Curve ,Drug Design ,Molecular Medicine ,Smoothened ,Protein Binding - Abstract
Through scaffold morphing of a known Smoothened antagonist Antag691, a series of novel phenyl imidazole derivatives were developed. Structure-activity-relationship studies and lead optimization led to the discovery of potent, selective and orally bioavailable Smoothened antagonist 19 that is suitable for in vivo studies.
- Published
- 2012