Synthesis and antibacterial activity of novel 4-pyrrolidinylthio carbapenems--I. 2-Alkoxymethyl derivatives.
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.
Azami
H
H
Medicinal Chemistry Research Laboratories, Fujisawa Pharmaceutical Co., Ltd, Osaka, Japan.
Tsutsumi
H
H
Matsuda
K
K
Barrett
D
D
Hattori
K
K
Nakajima
T
T
Kuroda
S
S
Kamimura
T
T
Murata
M
M
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
D015780:Carbapenems; C110103:FR 27743; D013845:Thienamycins; D004150:Dipeptidases; C038937:dipeptidase; D000077731:Meropenem