title: Synthesis and SAR of novel parenteral anti-pseudomonal cephalosporins: discovery of FR264205.
abstract: We describe herein the synthesis and biological evaluation of a series of novel cephalosporins with potent activity against Pseudomonas aeruginosa. Introduction of various amino groups to the 4-position of a 3-amino-2-methylpyrazole cephalosporin 3-side chain resulted in enhanced MIC values against multiple Pseudomonas aeruginosa strains and ultimately led to the discovery of FR264205 (15) with excellent anti-bacterial activity and weak convulsion effect by direct intracerebroventricular injection assay.
authors.affiliation: Chemistry Research Labs, Astellas Pharma Inc., 2-1-6 Kashima, Yodogawa-ku, Osaka 532-8514, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Toda
authors.forename: Hidenori
authors.initials: H
authors.lastname: Ohki
authors.forename: Toshio
authors.initials: T
authors.lastname: Yamanaka
authors.forename: Kenji
authors.initials: K
authors.lastname: Murano
authors.forename: Shinya
authors.initials: S
authors.lastname: Okuda
authors.forename: Kohji
authors.initials: K
authors.lastname: Kawabata
authors.forename: Kazuo
authors.initials: K
authors.lastname: Hatano
authors.forename: Keiji
authors.initials: K
authors.lastname: Matsuda
authors.forename: Keiji
authors.initials: K
authors.lastname: Misumi
authors.forename: Kenji
authors.initials: K
authors.lastname: Itoh
authors.forename: Kenji
authors.initials: K
authors.lastname: Satoh
authors.forename: Satoshi
authors.initials: S
authors.lastname: Inoue
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002442:Ceftazidime / Q000494:pharmacology; D002511:Cephalosporins / Q000009:adverse effects / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D051379:Mice; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000254:growth & development; D012640:Seizures / Q000139:chemically induced; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; C519491:ceftolozane; D002442:Ceftazidime