9-Dihydroerythromycins as non-antibiotic motilin receptor agonists

Yaoquan Liu; Yong Li; Yue Chen; Hao Zheng; Mark Claypool; David C Myles; Christopher W Carreras

doi:10.1016/j.bmcl.2010.08.030

9-Dihydroerythromycins as non-antibiotic motilin receptor agonists

Bioorg Med Chem Lett. 2010 Oct 1;20(19):5658-61. doi: 10.1016/j.bmcl.2010.08.030. Epub 2010 Aug 9.

Authors

Yaoquan Liu¹, Yong Li, Yue Chen, Hao Zheng, Mark Claypool, David C Myles, Christopher W Carreras

Affiliation

¹ Department of Chemistry, Kosan Biosciences, Inc, 3832 Bay Center Place, Hayward, CA 94545, USA. gyliu@comcast.net

PMID: 20801039
DOI: 10.1016/j.bmcl.2010.08.030

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.

MeSH terms

Amino Sugars / chemistry
Animals
Anti-Bacterial Agents / chemistry
Anti-Bacterial Agents / pharmacology
ERG1 Potassium Channel
Erythromycin / analogs & derivatives*
Erythromycin / chemical synthesis
Erythromycin / pharmacology
Ether-A-Go-Go Potassium Channels / metabolism
Rabbits
Receptors, Gastrointestinal Hormone / agonists*
Receptors, Gastrointestinal Hormone / metabolism
Receptors, Neuropeptide / agonists*
Receptors, Neuropeptide / metabolism
Tachyphylaxis / physiology

Substances

Amino Sugars
Anti-Bacterial Agents
ERG1 Potassium Channel
Ether-A-Go-Go Potassium Channels
Receptors, Gastrointestinal Hormone
Receptors, Neuropeptide
motilin receptor
desosamine
Erythromycin