Amdinocillin

Common Name Amdinocillin pivoxil Structural Formula ... 

Antibacterial activity is retained when the relatively complex amide side chains are replaced by a simple heterocycle amidine. The required reagent (7-2) is prepared by reaction of azepine formamide (7-1) with oxalyl chloride. Condensation of the product with 6-APA (2-4) leads to the formation of the amidine and thus amdinocillin (7-3) [11]. 

The unique biochemical aspects of amdinocillin (compound 21, Table 6-2) can be better comprehended following a consideration of the current understanding of bacterial membrane-associated penicillin-binding proteins (PBPs) and their relationship to the transpep-tidation reaction. 

Table 6-3 illustrates (for E. coli) the roles, if any, played by the seven PBPs in cell wall synthesis and cell morphology. Each is a distinct penicillin-sensitive enzyme whose inhibition has a particular consequence to the cell. For example, inactivation of PBP3 inhibits cell division and growth into filamentous cells. Death follows. PBP2 inactivation (the only specific target of mecillinam) in E. coli leads to spherical cell formation followed by lysis. Even though PBP2 is only 0.7% of total PBPs, amdinocillin s inhibition of it produces... 

Many in vitro studies have firmly established a synergism between sulbactam and various P-lactam antibiotics including piperacillin, amdinocillin, ampicillin, and penicillin G. These studies included bacterial strains resistant to ampicillin or penicillin G alone, which became sensitive upon addition of sulbactam. Carbenicillin-resistant Pseudomonas, however, was not potentiated. 

Crystals from methanol-acetone, tnp 156 (dec). [a) f + 285 Pivaloyloxymethyl ester, see Amdinocillin Pivoxil. therap CAT Antibacterial... 

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