ABSTRACT
A series of the novel oleandomycin 9-oximes has been prepared and characterized by spectroscopic data and X-ray analysis. The antibacterial in vitro activities of the oximes (6-10) were compared with that of oleandomycin (1). Among the novel derivatives the most active compound was 8(R)-methyloleandomycin-9-oxime (9) in contrast ot its 8(S)-isomer (10) which possessed only low potency. Some preliminary pharmacokinetic data of 9 confirmed its activity. Compound 9 has been advanced to further biological study.
Subject(s)
Oleandomycin/chemistry , Oleandomycin/pharmacology , Animals , Bacteria/drug effects , Crystallography , In Vitro Techniques , Magnetic Resonance Spectroscopy , Microbial Sensitivity Tests , Oleandomycin/analogs & derivatives , Oleandomycin/pharmacokinetics , Rats , Tissue DistributionABSTRACT
The novel 9a,11-cyclic carbamates (13-15) of 9-deoxo-9a-aza-9a-homoerythromycin A (4) have been prepared and characterized by 1H-1H and 1H-13C 2D NMR spectroscopy. When compared to azithromycin (1) or its 6-O-methyl derivative (2), the new bicyclic 15-membered azalides exhibited substantially decreased antibacterial activities in vitro.
Subject(s)
Azithromycin/analogs & derivatives , Bacteria/drug effects , Erythromycin/analogs & derivatives , Azithromycin/chemistry , Azithromycin/pharmacology , Erythromycin/chemistry , Erythromycin/pharmacology , Magnetic Resonance Spectroscopy , Microbial Sensitivity Tests , Structure-Activity RelationshipABSTRACT
A series of O-methylazithromycin derivatives have been synthesized and their antibacterial activities were compared with those of azithromycin (1). O-Methylation of 1 proceeded stepwise by the two main pathways beginning at the C-6 and C-11 hydroxyl groups, individually. Among O-methyl derivatives, 6-O-methylazithromycin A (11) was slightly less active than 1. The methylation of the secondary hydroxyl group at the C-11 position resulted surprisingly in an increase of their in vitro activity. The antibacterial activities of novel azalides decreased with increasing the number of the methyl groups introduced.
Subject(s)
Anti-Bacterial Agents/chemical synthesis , Erythromycin/analogs & derivatives , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Anti-Bacterial Agents/pharmacology , Azithromycin , Erythromycin/chemical synthesis , Erythromycin/pharmacology , Magnetic Resonance Spectroscopy , Methylation , Microbial Sensitivity Tests , Structure-Activity RelationshipABSTRACT
Antibacterial in vitro evaluation of 10-dihydro-10-deoxo-11-azaerythromycin A (5), the new 15-membered semi-synthetic macrolide antibiotic with nitrogen as additional atom in the aglycone ring of erythromycin A (1), was reported. Although amine (5) and its 13,14-cyclic carbonate (14) were less active than 1 against erythromycin-sensitive Staphylococcus aureus strains they showed advantageous properties against Gram-negative test organisms and clinical isolates. Also, a large number of acyl derivatives of 5 were synthesized and evaluated. N-11 monoacyl compounds exhibited 2 to 50 times lower in vitro antibacterial efficacy than the parent amine (5).
