Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
  • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
  • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
  • A61P31/04—Antibacterial agents

Definitions

• the subject of the present invention is new quinolones and more particularly quinolones substituted by a piperidine cycle.
• Z represents an amino radical
• RI represents a radical (lower alkyl optionally hydroxylated)
• an acyl radical derived from an organic carboxylic acid, from an alkyl carbonic acid, or from an alkylsulphonic acid, or an arylamino carbonyl radical of shape :
• Ar represents a mono or bicyclic aromatic radical optionally substituted by one, two or three substituents chosen from lower alkyl, halogens and trifluoromethyl.
• X represents oxygen or sulfur.
• R2 represents oxygen bound by a semi-polar valence and n is zero or one.
• n is zero or one.
• RI represents hydrogen or a lower alkyl radical, linear or branched, optionally substituted with a hydroxyl.
• NH AC in which Ac represents the remainder of an aliphatic, aromatic or cyclanic carboxylic acid having from I to 10 carbon atoms, the remainder of an alkylcarbonic acid or else the remainder of an alkylsulfonic acid optionally substituted by a hydroxyl or a trifluoromethyl radical.
• W is a C-H or N group
• B is hydrogen or an aromatic structure with 5 or 6 links.
• Z is hydrogen, a lower alkyl radical, a trifluoromethyl radical or a halogen, and p is 1, 2 or 3
• the compounds for which ZRI is a ureido function are those which are currently preferred.
• the compounds according to the invention can be salified by adding a mineral or organic base.
• the main salts which can be used are those of alkali metals, alkaline earth metals, ammonium, iron, aluminum, the alkylamine salts, the hydroxyalkylamine salts, the phenylalkylamine salts, the pyridylalkylamine salts, the salts of cyclanylamines, dicyclanylalkoylamine salts ...
• the sodium, lithium, ammonium, N-methylglucamine and tromethanol salts are those presently preferred.
• These compounds can also be salified with a strong mineral or organic acid when RI represents hydrogen, a lower alkyl radical or a lower (hydroxyalkyl) radical.
• the compounds according to the invention have very marked anti-bacterial properties, in particular against Gram positive bacteria.
• They can therefore be used effectively as drugs for bacterial infections of the digestive tract for the treatment of bacterial dysentria, travelers' diarrhea, or intestinal infections. They can also be used topically for the treatment of eye infections or infections of the ear canal.
• the compounds according to the invention will be used in the form of pharmaceutical compositions in which the active principle of general formula I or one of its salts, is added or mixed with an excipient or an inert non-toxic pharmaceutically acceptable vehicle.
• the most suitable pharmaceutical forms are those intended for administration by the digestive route such as oral solutions or suspensions, granules, capsules, naked or coated tablets, sugar-coated powders, flavored or not flavored powder sachets, sweetened or not, pills or cachets. Solutions, creams, ointments, salts can also be used for topical application as an external antibacterial agent.
• the average dosage depends mainly on the severity of the infection and the sensitivity of the microbial germ to the antibacterial agent.
• the unit dosage ranges from 100 to 600 mg per dose.
• the daily dosage ranges from 200 to 1200 mg divided into 2 to 4 doses.
• the invention also relates to a process for obtaining the compounds of general formula I which consists in reacting 6-fluoro T-chloro 1-ethyl 4-oxo 1,4-dihydroquinoIeine 3-carboxylic acid of formula II,
• the invention also relates to a process for converting the amino compound of formula III into urea or thiourea which consists in subjecting the compound of formula III to the action of an aryl isocyanate or isothiocyanate of formula
• the crystals formed are separated, which are drained and which are crystallized from a dimethylformamide-ethanol mixture.
• the inoculation is done by adding to each capsule 10 ⁇ l of a dilution in physiological water of an 18 H broth in brain heart broth such that each cup contains approximately 10 bacteria / ml.
• the minimum inhibitory concentration is read as the first concentration of non-culture-giving antibiotic, macroscopically visible after 18 H of incubation at 37 °.
• Example II The compound of Example II was found to be the most active. In particular with regard to Staphycococcus aureus:
• the MIC is 0.2 mcg / ml
• the CMB is 0.5 mcg / ml.
• the MIC is 8 mcg / ml
• the CMB is 8 mcg / ml

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• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Health & Medical Sciences (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Oncology (AREA)
• General Chemical & Material Sciences (AREA)
• Medicinal Chemistry (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Communicable Diseases (AREA)
• Pharmacology & Pharmacy (AREA)
• Life Sciences & Earth Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Applications Claiming Priority (2)

Publications (1)

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ID=9410326

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• 1991
  • 1991-03-01 FR FR9102585A patent/FR2673426B1/fr not_active Expired - Fee Related
• 1992
  • 1992-02-27 US US07/946,315 patent/US5332749A/en not_active Expired - Fee Related
  • 1992-02-27 AU AU14132/92A patent/AU1413292A/en not_active Abandoned
  • 1992-02-27 WO PCT/FR1992/000177 patent/WO1992015574A1/fr not_active Application Discontinuation
  • 1992-02-27 JP JP4506544A patent/JPH06503094A/ja active Pending
  • 1992-02-27 EP EP92907142A patent/EP0535184A1/fr not_active Withdrawn
  • 1992-10-30 FI FI924939A patent/FI924939A0/fi not_active Application Discontinuation

Non-Patent Citations (1)

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