ORGN 477 |
Synthesis of novel benzazepine oxazolidinone antibacterials
| Paul Johnson, Pfizer, 7254-209-608, 301 S. Henrietta Street, Kalamazoo, MI 49001 |
ZYVOX® (linezolid injection, tablets and oral suspension) is the first member of a new class of totally synthetic antibacterials for the treatment of Gram-positive bacteria, including the methicillin resistant S. aureus (MRSA) and S. epidermidis (MRSE), and vancomycin resistant enterococci (VRE). Continuing SAR studies of the oxazolidinone class of antibacterials have demonstrated a high tolerance for structural promiscuity in the area of the morpholine substituent including heterocycles with 5-, 6-, and 7-membered ring systems. Benzo-fused ring systems including indolines and tetrahydroquinolines have also been studied. Our search for new oxazolidinones to enhance potency and expand the spectrum of activity led us to synthesize a number of novel benzazepine oxazolidinones, exemplified by 2, to explore the effect of ring nitrogen position and N-substitution on antibacterial activity. |
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