Zoliflodacin

Source: Wikipedia, the free encyclopedia.
(Redirected from
AZD0914
)
Zoliflodacin
Clinical data
Other namesAZD0914; ETX0914
Pregnancy
category
  • Not classified yet
Routes of
administration		Oral
Drug classAntibiotic
Legal status
Legal status
JSmol)
  • C[C@@H]1CN2[C@H]([C@@H](O1)C)C3(CC4=C2C(=C5C(=C4)C(=NO5)N6[C@H](COC6=O)C)F)C(=O)NC(=O)NC3=O
  • InChI=1S/C22H22FN5O7/c1-8-7-33-21(32)28(8)17-12-4-11-5-22(18(29)24-20(31)25-19(22)30)16-10(3)34-9(2)6-27(16)14(11)13(23)15(12)35-26-17/h4,8-10,16H,5-7H2,1-3H3,(H2,24,25,29,30,31)/t8-,9+,10-,16+/m0/s1
  • Key:ZSWMIFNWDQEXDT-ZESJGQACSA-N

Zoliflodacin (development codes AZD0914 and ETX0914) is an experimental

Phase III clinical trials.[3][4]

Susceptible bacteria

Zoliflodacin has shown in vitro activity[5] against the following species of bacteria:

Pharmacology

Mechanism of action

Zoliflodacin is primarily active against both

Gram-negative bacteria. It functions by inhibiting DNA gyrase
, an enzyme necessary to separate bacterial DNA, thereby inhibiting cell replication.

History

Compound PNU-386607, discovered in a high-throughput screen for compounds with antibiotic activity.

A high throughput screening campaign aimed at identifying compounds with whole cell antibacterial activity performed at Pharmacia & Upjohn identified compound PNU-286607, a progenitor of Zoliflodacin, as having the desired activity.[6] Subsequent biological profiling of PNU-286607 showed that the compound inhibited DNA synthesis in susceptible bacteria, and analysis of mutants resistant to the compound's activity indicated that these compounds acted on DNA gyrase at a site distinct from that of the fluoroquinolone antibiotics.

Subsequent research at AstraZeneca led to the discovery that the nitroaromatic in PNU-286607 could be replaced with a fused benzisoxazole ring,[7] which allowed for an exploration of different groups at the 3-position of the heterocycle. This work was continued at Entasis Pharmaceuticals where extensive optimization resulted in the discovery of ETX0914,[8] which was renamed Zolifodacin in the course of its clinical development.

References

  1. PMID 30403954
    .
  2. PMID 26168713
    .
  3. ^ "GARDP and Innoviva Specialty Therapeutics Announce Completion of Patient Recruitment for Registrational Phase 3 Gonorrhea Treatment Trial". Innoviva Specialty Therapeutics. 23 May 2023. Retrieved 6 November 2023.
  4. ^ "Positive Results Announced in Largest Pivotal Phase 3 Trial of a First-In-Class Oral Antibiotic to Treat Uncomplicated Gonorrhea". Global Antibiotic Research & Development Partnership. 2023-11-01. Retrieved 2023-11-03.
  5. PMID 26168713
    .
  6. PMID 18519725
    .
  7. PMID 25286019
    .
  8. PMID 26168713
    .
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