title: Synthesis and properties of 2-(naphthosultamyl)methyl-carbapenems with potent anti-MRSA activity: discovery of L-786,392.
abstract: A series of 1beta-methyl-2-(naphthosultamyl)methyl-carbapenems bearing dicationic groups on the naphthosultamyl moiety was prepared and evaluated for activity against resistant gram-positive bacteria. Based on a combination of excellent in vitro antibacterial activity, acceptable mouse acute toxicity, and a desirable fragmentation pattern on beta-lactam ring opening, the analog 2g (L-786,392) was selected for extended evaluation.
authors: Department of Medicinal Chemistry, Merck Research Laboratories, Merck & Co., Inc., Rahway, New Jersey 07065-0900, USA.
authors: R W
authors: RW
authors: Ratcliffe
authors: R R
authors: RR
authors: Wilkening
authors: K J
authors: KJ
authors: Wildonger
authors: S T
authors: ST
authors: Waddell
authors: G M
authors: GM
authors: Santorelli
authors: D L
authors: DL
authors: Parker
authors: J D
authors: JD
authors: Morgan
authors: T A
authors: TA
authors: Blizzard
authors: M L
authors: ML
authors: Hammond
authors: J V
authors: JV
authors: Heck
authors: J
authors: J
authors: Huber
authors: J
authors: J
authors: Kohler
authors: K L
authors: KL
authors: Dorso
authors: E
authors: E
authors: St Rose
authors: J G
authors: JG
authors: Sundelof
authors: W J
authors: WJ
authors: May
authors: G G
authors: GG
authors: Hammond
mesh_terms: D000818:Animals; D015780:Carbapenems / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D004352:Drug Resistance, Microbial; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D006801:Humans; D007769:Lactams / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D051379:Mice; D008826:Microbial Sensitivity Tests; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D015780:Carbapenems; D007769:Lactams; D013844:Thiazoles; C117024:L 786392