The discovery and synthesis of 2-biphenylcarbapenems active against methicillin resistant staphylococci

✍ Scribed by Frank DiNinno; David A. Muthard; Thomas N. Salzmann; Joann Huber; Jean Kahan; Helmut Kropp

• Publisher: Elsevier Science
• Year: 1995
• Tongue: English
• Weight: 183 KB
• Volume: 5
• Category: Article
• ISSN: 0960-894X
• DOI: 10.1016/0960-894x(95)00149-n

✦ Synopsis

The discovery and synthesis of the arylcarbapenem 2b possessing potent activity against highly resistant strains of m_ethicillin resistant staphylococci are disclosed.

Recently, we reported on the in vitro antimicrobial activity of quatemary ammoniomethyl-phenylcarbapenems, such as 1, which were shown to be potent, broad spectrum antibacterial agents with stability toward mammalian dehydropeptidase. 1 In an attempt to further improve upon the activity profile and pharmacokinetics of 1, we focused on increasing serum protein binding by increasing the overall lipophilicity of the molecule, and thus initially targeted the biphenyl variants 2. Of the three possible biphenyl arrays, we opted to synthesize the more readily accessible para and meta dispositions utilizing the chemistry previously developed for the construction of the related carbapenems 1.