title: New anti-MRSA and anti-VRE carbapenems; synthesis and structure-activity relationships of 1beta-methyl-2-(thiazol-2-ylthio)carbapenems.
abstract: Discovery of novel antimicrobial agents effective against infections caused by drug-resistant pathogens is an important objective. In order to find a new parenteral carbapenem antibiotic, which has potent antibacterial activity especially against methicillin-resistant staphylococci, vancomycin-resistant enterococci and penicillin-resistant Streptococcus pneumoniae, a series of 1beta-methylcarbapenems with thiazol-2-ylthio groups at the C-2 position have been synthesized. Structure-activity relationships were investigated which led to SM-197436 (27), SM-232721 (44) and SM-232724 (41), being selected for further evaluation.
authors.affiliation: Sumitomo Pharmaceuticals Research Division, Osaka, Japan. sunagawa@sumitomopharm.co.jp
authors.forename: Makoto
authors.initials: M
authors.lastname: Sunagawa
authors.forename: Masanori
authors.initials: M
authors.lastname: Itoh
authors.forename: Katsumi
authors.initials: K
authors.lastname: Kubota
authors.forename: Akira
authors.initials: A
authors.lastname: Sasaki
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Ueda
authors.forename: Peter
authors.initials: P
authors.lastname: Angehrn
authors.forename: Anne
authors.initials: A
authors.lastname: Bourson
authors.forename: Erwin
authors.initials: E
authors.lastname: Goetschi
authors.forename: Paul
authors.initials: P
authors.lastname: Hebeisen
authors.forename: Rudolf L
authors.initials: RL
authors.lastname: Then
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015780:Carbapenems / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D016983:Enterococcus / Q000187:drug effects*; D006801:Humans; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests / Q000379:methods; D010403:Penicillin Resistance; D013211:Staphylococcus aureus / Q000187:drug effects*; D013296:Streptococcus pneumoniae / Q000187:drug effects; D013329:Structure-Activity Relationship; D020713:Vancomycin Resistance
chemical_list: C467216:3-((4-(2,5-dihydro-1H-pyrrol-3-yl)-1,3-thiazol-2-yl)thio)-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo(3.2.0)hept-2-ene-2-carboxylic acid; C467218:6-(1-hydroxyethyl)-3-((4-(2-(hydroxymethyl)-1,2,3,6-tetrahydropyridin-4-yl)-1,3-thiazol-2-yl)thio)-4-methyl-7-oxo-1-azabicyclo(3.2.0)hept-2-ene-2-carboxylic acid; C467217:6-(1-hydroxyethyl)-4-methyl-3-((4-(2-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1,3-thiazol-2-yl)thio)-7-oxo-1-azabicyclo(3.2.0)hept-2-ene-2-carboxylic acid; D000900:Anti-Bacterial Agents; D015780:Carbapenems