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: H Azami, H Tsutsumi, K Matsuda, D Barrett, K Hattori, T Nakajima, S Kuroda, T Kamimura, M Murata
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 5 Issue 11 Pg. 2069-87 (Nov 1997) ISSN: 0968-0896 [Print] England
• PMID: 9416424 (Publication Type: Journal Article)

Chemical References

• Carbapenems
• FR 27743
• Thienamycins
• Dipeptidases
• dipeptidase
• Meropenem

Topics

• Animals
• Carbapenems (chemical synthesis, chemistry, 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, chemistry, pharmacology)
• Urine (chemistry)