Synthesis and structure-activity relationships of novel THF 1β-methylcarbapenems

• Published in: Bioorganic & medicinal chemistry letters Vol. 7; no. 13; pp. 1671 - 1676
• Main Authors: Lin, Yang-I, Bitha, Panayota, Sakya, Subas M., Strohmeyer, Timothy W., Li, Zhong, Lee, Ving J., Lang, Stanley A., Yang, Youjun, Bhachech, Niraja, Weiss, William J., Petersen, Peter J., Jacobus, Nilda V., Bush, Karen, Testa, Raymond T., Tally, Francis P.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 08-07-1997; Elsevier
• Subjects: Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Biological and medical sciences; Medical sciences; Pharmacology. Drug treatments; Enethiol sulfide; Rodentia; Furan derivatives; Oral administration; Bioavailability; In vitro; Antimicrobial agent; Cis stereoisomer; Penicillin derivatives; Stereoselectivity; In vivo; Vertebrata; Carbapenem derivatives; Mammalia; Structure activity relation; Mouse; Animal; Secondary alcohol; Pharmacokinetics; Chemical synthesis; Primary amine
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(97)00282-5

A series of twelve highly active aminomethyl-THF 1β-methylcarbapenems
3a-1 were synthesized. Of these, carbapenems
3a-f demonstrated a spectrum of antimicrobial activity comparable to those of imipenem and meropenem with the exception of only moderate anti-pseudomonal activity. Most importantly, they demonstrated moderate intrinsic oral activity against an
E. coli infection in mice.
A series of twelve highly active aminomethyl-THF 1β-methylcarbapenems
3a-l were synthesized. Of these, carbapenems
3a-f demonstrated a spectrum of antimicrobial activity comparable to those of imipenem and meropenem with the exception of only moderate anti-pseudomonal activity. Most importantly, they demonstrated moderate intrinsic oral activity against an
E. coli infection in mice.