Grepafloxacin

Source: Wikipedia, the free encyclopedia.
Grepafloxacin
Clinical data
AHFS/Drugs.comMultum Consumer Information
ATC code
Pharmacokinetic data
Protein binding50%
Identifiers
  • (RS)-1-Cyclopropyl-6-fluoro-5-methyl-7-(3-methylpiperazin-1-yl)-4-oxo-quinoline-3-carboxylic acid
JSmol)
ChiralityRacemic mixture
  • O=C(O)\C2=C\N(c1cc(c(F)c(c1C2=O)C)N3CC(NCC3)C)C4CC4
  • InChI=1S/C19H22FN3O3/c1-10-8-22(6-5-21-10)15-7-14-16(11(2)17(15)20)18(24)13(19(25)26)9-23(14)12-3-4-12/h7,9-10,12,21H,3-6,8H2,1-2H3,(H,25,26) checkY
  • Key:AIJTTZAVMXIJGM-UHFFFAOYSA-N checkY
  (verify)

Grepafloxacin (trade name Raxar,

sudden death.[3]

Clinical uses

Grepafloxacin was used for treating exacerbations of chronic bronchitis caused by susceptible bacteria (e.g. Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis),[4][5][6] community-acquired pneumonia (including those, in addition to the above germs, caused by Mycoplasma pneumoniae)[7][8] gonorrhea and non-gonococcal urethritis and cervicitis (for example caused by Chlamydia trachomatis or Ureaplasma urealyticum).[9][10]

Synthesis

The preparation of quinolones bearing a substituent at position 5 is complicated by the greater electrophilic character of the 8 position. One scheme for resolving the problem consists in blocking access to position 8 by first adding a readily removable group to that center.

Grepafloxacin synthesis:[11][12]

The scheme starts with the conversion of the carboxylic acid in (1) to its dimethyloxazoline derivative (3) by reaction with the

cesium fluoride breaks the carbon–silicon bond, removing the silyl group; aqueous acid then hydrolyzes the oxazoline to afford the free acid (6). This last intermediate is then taken on to the quinolone (9) [13] by essentially the same scheme as that used to prepare difloxacin, with the difference that the chain elongation is by means of Grignard reagent of ethyl bromoacetate. Treatment of (9) with 2-methylpiperazine proceeds by reaction at the less hindered of the two amino groups; saponification
then affords grepafloxacin (10).

Stereochemistry

Grepafloxacin contains a stereocenter and consists of two enantiomers. This is a

racemate
, ie a 1: 1 mixture of (R)- and the (S)-forms:

Enantiomers of grepafloxacin

(R)-grepafloxacin
CAS number: 146761-68-4
(S)-grepafloxacin
CAS number: 146761-69-5

See also

  • Quinolones

References

  1. ^ "Glaxo Wellcome voluntary withdrawn Raxar (Grepafloxacin)" (PDF). Food and Drug Administration. Retrieved 2014-10-12.
  2. ^ "Withdrawal of Product: RAXAR (grepafloxacin HCl) 600 mg Tablets, 400 mg Tablets, and 200 mg Tablets". U.S. Food and Drug Administration. Retrieved 2014-10-12.
  3. PMID 14992418
    .
  4. PMID 9449270
    .
  5. PMID 9484875
    .
  6. PMID 10588313
    .
  7. PMID 9484876
    .
  8. PMID 10719006
    .
  9. PMID 9484871
    .
  10. PMID 9785106
    .
  11. PMID 2002456
    .
  12. ^ WO 8906649 ; eidem, U.S. patent 4,920,120 (1989, 1990 both to Warner-Lambert).
  13. doi:10.1002/jhet.5570270616
    .
Retrieved from "https://en.wikipedia.org/w/index.php?title=Grepafloxacin&oldid=1193710359"