title: Synthesis and antibacterial activity of a novel series of acylides: 3-O-(3-pyridyl)acetylerythromycin A derivatives.
abstract: A novel series of acylides, 3-O-(aryl)acetylerythromycin A derivatives, were synthesized and evaluated. These compounds have significant potent antibacterial activity against not only Gram-positive pathogens, including inducibly macrolide-lincosamide-streptogramin B (MLS(B))-resistant and efflux-resistant strains, but also Gram-negative pathogens, such as H. influenzae. 6,9:11,12-dicarbonate acylide 47 (FMA0122) was twice as active against H. influenzae than azithromycin, whereas it showed only moderate in vivo efficacy in mouse protection tests. However, the 11,12-carbamate acylide 19 (TEA0929), which showed potent antibacterial activity against almost all of the main causative pathogens of community-acquired pneumonia tested, exhibited excellent in vivo efficacy comparable to those of second-generation macrolides.
authors.affiliation: Medicinal Research Laboratories, Taisho Pharmaceutical Co. Ltd., 1-403 Yoshino-cho, Kita-ku, Saitama-shi, Saitama 331-9530, Japan. tetsuya.tanikawa@po.rd.taisho.co.jp
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Tanikawa
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Asaka
authors.forename: Masato
authors.initials: M
authors.lastname: Kashimura
authors.forename: Keiko
authors.initials: K
authors.lastname: Suzuki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sugiyama
authors.forename: Masakazu
authors.initials: M
authors.lastname: Sato
authors.forename: Kazuya
authors.initials: K
authors.lastname: Kameo
authors.forename: Shigeo
authors.initials: S
authors.lastname: Morimoto
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nishida
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D019540:Area Under Curve; D024901:Drug Resistance, Multiple, Bacterial; D004917:Erythromycin / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006193:Haemophilus influenzae / Q000187:drug effects; D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D013203:Staphylococcal Infections / Q000401:mortality / Q000517:prevention & control; D013211:Staphylococcus aureus / Q000187:drug effects; D013237:Stereoisomerism; D013290:Streptococcal Infections / Q000401:mortality / Q000517:prevention & control; D013296:Streptococcus pneumoniae / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: C475517:5-O-desosaminyl-3-O-(3-pyridyl)acetyl-6-O-methylerythronolide A 11,12-cyclic carbamate; C475516:5-O-desosaminyl-9-dihydro-3O-(3-pyridyl)acetylerythronolide A 6,9-11,12-dicyclic carbonate; D000900:Anti-Bacterial Agents; D018942:Macrolides; D004917:Erythromycin