title: Structure of grepafloxacin relative to activity and safety profile.
abstract: A comparison of the structure of ciprofloxacin and grepafloxacin shows that the two compounds are similar, with two exceptions: grepafloxacin has a methyl group at the 5 position and a methyl group attached to the 7-piperazinyl substituent. At the 1 position, both compounds have a cyclopropyl group, which is important for potency, but limits anaerobic activity. The methylpiperazine at position 7 in grepafloxacin is associated with its enhanced Gram-positive activity and long half-life. The methyl group at R5 is also thought to enhance Gram-positive activity. Ciprofloxacin's piperazine group at the 7 position is associated with good Gram-negative activity. Grepafloxacin's Gram-negative activity is comparable to that of ciprofloxacin's against Haemophilus influenzae, Moraxella catarrhalis and enteric Gram-negative bacilli. Studies of resistance development to fluoroquinolones suggest that grepafloxacin is associated with a reduced selection of resistance in Staphylococcus aureus, which is possibly related to the inhibition or avoidance of efflux transport by NorA.
authors.affiliation: Infectious Disease Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: David C.
authors.initials: DC
authors.lastname: Hooper