title: The role of the 4''-hydroxyl on motilin agonist potency in the 9-dihydroerythromycin series.
abstract: The role of the erythromycin 4''-hydroxyl group has been explored on the motilin agonist potential in the 9-dihydroerythromycin series of motilides. The compounds show potencies 2- to 4-fold superior to the corresponding hydroxylated compounds. The relationship is maintained when the 9-hydroxyl is alkylated to generate the corresponding 4''-deoxy-9-O-acetamido-9-dihydroerythromycins. However, concomitant with this increase in potency is an increase in hERG inhibition.
authors.affiliation: Department of Chemistry, Kosan Biosciences, Inc., Hayward, California 94545, USA.
authors.forename: Yaoquan
authors.initials: Y
authors.lastname: Liu
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Carreras
authors.forename: Mark
authors.initials: M
authors.lastname: Claypool
authors.forename: David C
authors.initials: DC
authors.lastname: Myles
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Shaw
mesh_terms: D002478:Cells, Cultured; D000072237:ERG1 Potassium Channel; D004917:Erythromycin / Q000737:chemistry* / Q000494:pharmacology*; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors*; D005765:Gastrointestinal Agents / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D017665:Hydroxyl Radical / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D009037:Motilin / Q000819:agonists*
chemical_list: D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D005765:Gastrointestinal Agents; C000606913:KCNH2 protein, human; D017665:Hydroxyl Radical; D009037:Motilin; D004917:Erythromycin