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-1β-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 antibacteria...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry 1997-11, Vol.5 (11), p.2069-2087
Main Authors: Azami, Hidenori, Tsutsumi, Hideo, Matsuda, Keiji, Barrett, David, Hattori, Kouji, Nakajima, Takashi, Kuroda, Satoru, Kamimura, Toshiaki, Murata, Masayoshi
Format: Article
Language:English
Subjects:
Animals
Carbapenems - chemical synthesis
Carbapenems - chemistry
Carbapenems - pharmacology
Dipeptidases - metabolism
Drug Stability
Male
Meropenem
Mice
Mice, Inbred ICR
Microbial Sensitivity Tests
Pseudomonas Infections - drug therapy
Rats
Staphylococcal Infections - drug therapy
Thienamycins - chemical synthesis
Thienamycins - chemistry
Thienamycins - pharmacology
Urine - chemistry
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Summary:The synthesis and in vitro antibacterial activity of a novel series of 2-alkoxymethyl-4-pyrrolidinylthio-1β-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. The synthesis and in vitro antibacterial activity and stability to human DHP-I of a novel series of alkoxymethyl-substituted carbapenems 19 ar
ISSN:0968-0896
1464-3391
DOI:10.1016/S0968-0896(97)00142-9