Motilides, macrolides with gastrointestinal motor stimulating activity. II. Quaternary N-substituted derivatives of 8,9-anhydroerythromycin A 6,9-hemiacetal and 9,9-dihydroerythromycin A 6,9-epoxide.
A series of quaternary ammonium derivatives of 8,9-anhydroerythromycin A 6,9-hemiacetal (1) and 9,9-dihydroerythromycin A 6,9-epoxide (2) has been prepared and tested for antimicrobial activity and gastrointestinal motor stimulating (GMS) activity in the dog (in vivo). The GMS activity is enhanced markedly when small alkyl halides and unsaturated alkyl halides such as allyl bromide and propargyl bromide are added to the dimethylamino group of 1. Among them, N-propargyl-8,9-anhydroerythromycin A 6,9-hemiacetal bromide (3) exhibits GMS activity 2890 times stronger than that of erythromycin A and is completely devoid of antimicrobial activity. The potency of 3 is comparable to that of synthetic motilin both in vitro and in vivo.
Sunazuka
T
T
Tsuzuki
K
K
Marui
S
S
Toyoda
H
H
Omura
S
S
Inatomi
N
N
Itoh
Z
Z
D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis; D001419:Bacteria / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D004285:Dogs; D004917:Erythromycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D005769:Gastrointestinal Motility / Q000187:drug effects*; D066298:In Vitro Techniques; D008826:Microbial Sensitivity Tests; D011817:Rabbits; D013268:Stimulation, Chemical
D000900:Anti-Bacterial Agents; D004917:Erythromycin