title: Synthesis and antibacterial activity of novel 4-pyrrolidinylthio carbapenems--I. 2-Alkoxymethyl derivatives.
abstract: The synthesis and in vitro antibacterial activity of a novel series of 2-alkoxymethyl-4-pyrrolidinylthio-1 beta-methyl carbapenems are described. As a result of these studies, we discovered that FR27743 (19j) containing a novel 2-fluoroethoxymethyl substituent possesses a broad spectrum of antibacterial activity against both Gram-positive and Gram-negative organisms, including Pseudomonas aeruginosa. Furthermore, FR27743 exhibited excellent stability against renal dehydropeptidase-I (DHP-I), good urinary recovery, and superior in vivo activity compared to that for Meropenem against several systemic infections.
authors.affiliation: Medicinal Chemistry Research Laboratories, Fujisawa Pharmaceutical Co., Ltd, Osaka, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Azami
authors.forename: H
authors.initials: H
authors.lastname: Tsutsumi
authors.forename: K
authors.initials: K
authors.lastname: Matsuda
authors.forename: D
authors.initials: D
authors.lastname: Barrett
authors.forename: K
authors.initials: K
authors.lastname: Hattori
authors.forename: T
authors.initials: T
authors.lastname: Nakajima
authors.forename: S
authors.initials: S
authors.lastname: Kuroda
authors.forename: T
authors.initials: T
authors.lastname: Kamimura
authors.forename: M
authors.initials: M
authors.lastname: Murata
mesh_terms: D000818:Animals; D015780:Carbapenems / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004150:Dipeptidases / Q000378:metabolism; D004355:Drug Stability; D008297:Male; D000077731:Meropenem; D051379:Mice; D008813:Mice, Inbred ICR; D008826:Microbial Sensitivity Tests; D011552:Pseudomonas Infections / Q000188:drug therapy; D051381:Rats; D013203:Staphylococcal Infections / Q000188:drug therapy; D013845:Thienamycins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D014556:Urine / Q000737:chemistry
chemical_list: D015780:Carbapenems; C110103:FR 27743; D013845:Thienamycins; D004150:Dipeptidases; C038937:dipeptidase; D000077731:Meropenem