Approaches to the synthesis of immunolides: selective immunomodulatory macrolides for cystic fibrosis.
The discovery of the clinical effectiveness of erythromycin and azithromycin in inflammatory airway diseases has inspired the discovery and development of macrolides with selective immunomodulatory activity. Erythromycin degradation continues to be a source of novel macrolides with a variety of selective biological activities. New technologies for drug discovery based in the emerging field of combinatorial biosynthesis provide the medicinal chemist with novel approaches toward the discovery of novel macrolides. Recent efforts to integrate synthetic organic medicinal chemistry with combinatorial biosynthesis have expanded the number of techniques available for macrolide synthesis.
Fecik
Robert A
RA
University of Minnesota, Department of Medicinal Chemistry, 308 Harvard Street SE, 8-101 WDH Minneapolis, MN 55455-0353, USA. fecik001@umn.edu
Nguyen
Phuongdiep L
PL
Venkatraman
Lakshmanan
L
D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000627:therapeutic use; D017963:Azithromycin / Q000138:chemical synthesis / Q000627:therapeutic use; D020650:Combinatorial Chemistry Techniques; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000276:immunology; D015195:Drug Design; D004917:Erythromycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000627:therapeutic use; D006801:Humans; D007155:Immunologic Factors / Q000138:chemical synthesis* / Q000627:therapeutic use; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology; D018942:Macrolides / Q000138:chemical synthesis* / Q000627:therapeutic use
D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D007155:Immunologic Factors; D018942:Macrolides; D004917:Erythromycin; D017963:Azithromycin; C003145:picromycin