title: Design, synthesis, and structure-activity-relationship of phenyl imidazoles as potent Smoothened antagonists.
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.
authors.affiliation: Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, USA.
authors.forename: Dai
authors.initials: D
authors.lastname: Cheng
authors.forename: Dong
authors.initials: D
authors.lastname: Han
authors.forename: Wenqi
authors.initials: W
authors.lastname: Gao
authors.forename: Qihui
authors.initials: Q
authors.lastname: Jing
authors.forename: Jiqing
authors.initials: J
authors.lastname: Jiang
authors.forename: Yongqin
authors.initials: Y
authors.lastname: Wan
authors.forename: Nathan P
authors.initials: NP
authors.lastname: Englund
authors.forename: Tove
authors.initials: T
authors.lastname: Tuntland
authors.forename: Xu
authors.initials: X
authors.lastname: Wu
authors.forename: Shifeng
authors.initials: S
authors.lastname: Pan
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D019540:Area Under Curve; D015195:Drug Design; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D051379:Mice; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors*; D000072086:Smoothened Receptor; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D007093:Imidazoles; D043562:Receptors, G-Protein-Coupled; C491023:SMO protein, human; D000072086:Smoothened Receptor; C029899:imidazole