Synthesis, in vitro and in vivo activity of novel 9-deoxo-9a-aza-9a-homoerythromycin A derivatives; A new class of macrolide antibiotics, the azalides.
Year: 1988
Type: article
Abstract: A series of erythromycin A-derived semisynthetic antibiotics, featuring incorporation of a basic nitrogen atom into a ring expanded (15-membered) macrocyclic lactone, have been prepared and biologically evaluated. Semisynthetic modifications focused upon (1) varied substitution at the macrocyclic ring nitrogen and (2) epimerization or amine substitution at the C-4'' hydroxyl site within the cladinose sugar. In general, the new azalides exhibit improved Gram-negative potency, expanding the spectrum of erythromycin A to fully include Haemophilus influenzae and Neisseria gonorrhoeae. When compared to erythromycin A, the azalides exhibit substantially increased half-life and area-under-the-curve values in all species studied. The overall in vitro/in vivo performance of N-methyl, C-4'' epimers 3a and 9; and C-4'' amine 11 identify these compounds as the most interesting erythromycin A-superior agents. Compound 3a has been advanced to clinical study.
Source: The Journal of Antibiotics
Authors: G. MICHAEL BRIGHT, ARTHUR A. NAGEL, JON BORDNER, KISHOR A. DESAI, JOSEPH N. DIBRINO, JOLANTA NOWAKOWSKA, LAWRENCE VINCENT, RICHARD M. WATROUS, FRANK C. SCIAVOLINO, ARTHUR R. ENGLISH, JAMES A. RETSEMA, MARGARET R. ANDERSON, LORI A. BRENNAN, ROBERTA J. BOROVOY, CAROLINE R. CIMOCHOWSKI, JAMES A. FAIELLA, ARTHUR E. GIRARD, DENNIS GIRARD, CAROL HERBERT, MARY MANOUSOS, RACHEL MASON
Institution: Pfizer (United States)
Language: English
Subfield: Applied Microbiology and Biotechnology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W2003567541