150785-53-8Relevant articles and documents
Synthesis of 4"-Deoxy Motilides: Identification of a Potent and Orally Active Prokinetic Drug Candidate
Lartey, Paul A.,Nellans, Hugh N.,Faghih, Ramin,Petersen, Albert,Edwards, Carla M.,et al.
, p. 1793 - 1798 (1995)
As an approach to discovering highly potent motilides with oral activity, novel 4"-deoxy derivatives of 8,9-anhydroerythromycin 6,9-hemiacetal were designed, synthesized, and evaluated for their gastrointestinal prokinetic activities.These compounds were orders of magnitude more potent than their 4"-hydroxy analogs in inducing smooth muscle contractions in an in vitro rabbit duodenal assay.Removal of the 12-hydroxy group, which was aimed at improving oral bioavailability, also afforded furhther potentiation in in vitro activity, leading to the identification of 8,9-anhydro-4"-deoxy-3'-N-desmethyl-3'-N-ethylerythromycin B 6,9-hemiacetal (ABT-229) as a potential prokinetic drug.ABT-229 was >300 000 times more potent than erythromycin in vitro and had 39percent oral bioavailability in dog compared to its 4",12-dihydroxy congener (EM-523), which was only 400 times more potent than erythromycin and had relatively low (1,4percent) oral bioavailability.
