title: 9-Dihydroerythromycins as non-antibiotic motilin receptor agonists.
abstract: A series of 9-dihydroerythromycin A and B analogues with modification of the desosamine nitrogen have been synthesized and screened for motilin agonist activity, antibiotic activity, tachyphylaxis and hERG channel current inhibition. Small alkyl groups resulted in the potency while compounds with a primary or secondary amine resulted in the low motilin agonist potency. Several compounds were identified as non-antibiotic motilin receptor agonists with minimal tachyphylaxis and low hERG interaction.
authors.affiliation: Department of Chemistry, Kosan Biosciences, Inc, 3832 Bay Center Place, Hayward, CA 94545, USA. gyliu@comcast.net
authors.forename: Yaoquan
authors.initials: Y
authors.lastname: Liu
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.forename: Yue
authors.initials: Y
authors.lastname: Chen
authors.forename: Hao
authors.initials: H
authors.lastname: Zheng
authors.forename: Mark
authors.initials: M
authors.lastname: Claypool
authors.forename: David C
authors.initials: DC
authors.lastname: Myles
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Carreras
mesh_terms: D000606:Amino Sugars / Q000737:chemistry; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D000072237:ERG1 Potassium Channel; D004917:Erythromycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D051638:Ether-A-Go-Go Potassium Channels / Q000378:metabolism; D011817:Rabbits; D011964:Receptors, Gastrointestinal Hormone / Q000819:agonists* / Q000378:metabolism; D018013:Receptors, Neuropeptide / Q000819:agonists* / Q000378:metabolism; D013618:Tachyphylaxis / Q000502:physiology
chemical_list: D000606:Amino Sugars; D000900:Anti-Bacterial Agents; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D011964:Receptors, Gastrointestinal Hormone; D018013:Receptors, Neuropeptide; C050802:motilin receptor; C110125:desosamine; D004917:Erythromycin