The Polymer-supported and Combinatorial Synthesis of ß-lactam Compounds: An Update

LABORDE, MARÍA DE LOS ANGELES; MATA, ERNESTO G

Minirev Med Chem

Bentham Science

Año: 2006 vol. 6 p. 107 - 118

1389-5575

Solid-phase organic synthesis (SPOS) has become an effective synthetic tool for the preparation of combinatorial libraries of non-oligomeric small molecules. It is used for the generation of compounds requiered for screening against diverse biological targets, being a key technology in order to accelerate lead generation and lead optimization in drug discovery. On the other hand, b-Lactam ring is an active acylating agent whose effectiveness in a large number of clinically important therapeutic areas has been clearly demonstrated. Owing to their high efficacy and extremely safe toxicological profile, b-lactams antibiotics are the first choice for bacterial infectious diseases. Moreover, b-lactam compounds have also showed other biological activities that include inhibition of prostate specific antigen, thrombin, human cytomegalovirus protein, human leukocyte elastase and cholesterol absorption. Thus, the application of combinatorial and related methodologies to the chemistry of the b-lactam ring has been recognized as is a very attractive challenge by different research groups around the world. This review covers the solid-phase and combinatorial chemistry related to mono- and multicyclic b-lactam compounds that has been reported in the literature in the last five years.