This document discusses urinary tract anti-infective agents. It classifies these agents based on their chemical structure into quinolone derivatives, nitrofuran derivatives, methenamine and its salts, and urinary analgesics. It provides details on various quinolone derivatives like norfloxacin, ciprofloxacin, and nalidixic acid. It describes the structure-activity relationships and mechanisms of action of quinolone derivatives and nitrofurantoin. It lists the uses of various urinary tract anti-infective agents in treating infections like UTIs, pneumonia, and pelvic inflammatory disease.

1. URINARY TRACT
ANTI-INFECTIVE
AGENTS
BY
KENCHA SWATHI
ASSISTANT PROFESSOR
Swathi Pharma Jnan

2. URINARY TRACT ANTI-INFECTIVE
AGENTS
Definition: Antibacterial agents that fail to achieve adequate concentrations in
the plasma or tissues for the treatment of systemic infections following oral or
parentral administration are concentrated in the urine,where they can be
effective for eradicating urinary tract infections.
Swathi Pharma Jnan

3. CLASSIFICATION
Based on chemical structure:
1.Quinolone derivatives – Nalidixic acid,Norfloxacin,Ciprofloxacin
2.Nitrofuran derivatives – Nitrofurantoin
3.Methenamine and its salts – Hexamine(Hexa methylene Tetramine)
4.Urinary analgesics – Phenyl azo pyridine
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4. QUINOLONE DERIVATIVES
• These are isosteric heterocyclic groupings which includes –
a.Quinolones –Norfloxacin
Ciprofloxacin,Sparfloxacin,Lomefloxacin,O-floxacin
b.Naphthyridines(1,8-Napthyridines) – Nalidixic acid,Enoxacin
c.Cinnolines(1,2-Napthyridines) – Cinnoxacin
Quinolone derivatives contain isosteric substitution of carbon by nitrogen.
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5. SAR OF QUINOLONES
• 1,4-dihydro 4-oxo pyridine 3-carboxylic acid is essential for anti-bacterial
activity.
• Pyridone should be fused with aromatic ring for showing activity.
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6. • Isosteric replacements of nitrogen for carbon atoms at position
2(cinnolines),position 5(1,5-naphthyridines),position 6(1,6-
naphthyridines),position 8(1,8-naphthyridines) are consistent with retained
antibacterial activity.
• 1,7-naphthyridines and 1,3-naphthyridines are not active.
• 1,2-Naphthyridines(Cinnolines) are showing better activity.
Eg:
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7. • 1,5-naphthyridines have isosteric substitution of carbon with nitrogen at 5th
position.
Eg:
• 1,8-Naphthyridines shows better activity compared to other napthyridines.
Eg: Nalidixic acid
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8. • Introduction of substituents at position 2 greatly abolishes the activity.
• Introduction of substituents at position 5,6,7 (especially at 8) of anneulated ring
will result in compounds with good activity.
• Normally at 7th position piperazinyl (saturated pyrazine)structure is common.
• 3-Amino pyrrolidinyl(saturated pyrrole) substituents at position 7 enhances the
activity of quinolone class against “Pseudomonas aerogenosa”.
Eg: Enoxacin
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9. • F atom substitution at position 6 also significantly enhances the antibacterial
activity.
• Alkyl substitution at position 1 is essential for activity with lower alkyl groups like
methyl,ethyl,cyclopropyl group containing compounds have progressively greater
potency.
Eg:Ciprofloxacin
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10. • If we have aryl substitution at position 1 is also consisting with the antibacterial
activity with 2,4-difluorogroups produces optimum activity.
• Ring condensation compounds are active
Eg: Cinnoxacin - 6,7-fusion & O-Floxacin -1,8 condensation
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11. • 6-Fluoro quinolones having basic moieties like 1-piperidino-3-amino,1-pyrrolidino or
similar basic moiety at the 7th position will have some CNS effects such as
irritability,tremors,sleep disorders,vertigo,anxiety,agitation and convulsions etc.,
Eg: O-Floxacin
• Quinolones possessing additional halogen atom at 8th position shows along with
CNS effects they also exihibit phototoxicity.
• One more F at 8th position causes sensitive towards photolight.
Eg: Lomefloxacin
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12. • Quinolone derivatives having an amino group or methoxy group either at 5th or 8th
position will have lowest incidence of photo light.
Eg: Sparfloxacin
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13. NORFLOXACIN
USES: In the treatment of UTI’s caused by E.Coli,Pneumonia,Enterobacter
species,Proteus species and staphylococcus aureus.
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14. SPARFLOXACIN
USES: To treat skin and soft tissue infections.
To treat lower respiratory tract infetions like bronchitis and bacterial
pneumonia,pelvic inflammatory disease caused by gonorrhoea,chlamydia
species.
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15. CIPROFLOXACIN
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USES: To treat bacterial gastroenteritis caused by gram –ve bacteria .
It is widely used for the treatment of respiratory tract infections such as pneumonia
caused by gram –ve bacteria.
To treat UTI ,venereal disease. For post exposure treatment of inhalation anthrax.

16. LOMEFLOXACIN
USES: To treat Urinary tract infections
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17. O-FLOXACIN
USES: To treat lower respiratory tract infections and pelvic inflammatory
disease.
To treat UTI’s caused by gram-ve bacteria and for prostatitis caused by
E.Coli.
To treat soft tissue /skin infections caused by staphylococcus,streptococci .Swathi Pharma Jnan

18. NALIDIXIC ACID
USES:In the treatment of UTI’s in which gram –ve bacteria predominates.
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19. ENOXACIN
USES: To treat urinary tract infections
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20. CINNOXACIN
USES: To treat UTI infection in which gram-ve bacteria is susceptible .
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21. NITROFURANTOIN
USES: To treat bacterial infections.
Antiprotozoal drug
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22. METHENAMINE(HEXAMETHYLENE
TETRAMINE)
Uses: Used as urinary antiseptic and for the treatment of chronic UTI’s.
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23. PHENYL AZO PYRIDINE
USES: Used as local analgesic which acts on the mucosa of urinary tract.
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24. MOA OF QUINOLONES
• Quinolones produces their antibacterial activity by inhibiting the synthesis of
DNA due to the inhibition of bacterial DNA gyrase(topoisomerase-2),an
enzyme responsible for introducing negative supercoils into circular duplex
DNA.
• Negative supercoiling relieves torsional stress of unwinding helical DNA and
there by allows transcription and replication to occur .
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25. MOA OF NITROFURANTOIN
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26. SYNTHESIS OF NITROFURANTOIN
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5-Nitrofurfural 1-Amino
hydantoin Nitrofurantoin
NaOH
-H₂O