Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
  • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
  • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
  • C07D215/38—Nitrogen atoms
  • C07D215/42—Nitrogen atoms attached in position 4
  • C07D215/44—Nitrogen atoms attached in position 4 with aryl radicals attached to said nitrogen atoms
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system

Definitions

• the present invention relates to certain salts of a quinoline compound, pharmaceutical compositions containing them and their use in therapy as inhibitors of gastric acid secretion.
• EP-330485-A discloses a series of 4-amino-3- acylquinoline derivatives in which the quinoline is substituted in the 8-position by, for example, hydroxyalkyl and hydroxyalkoxy groups.
• the compounds of EP 330485-A have been found to have poor dissolution rates in water and, as a consequence, could potentially exhibit poor bioavailability in vivo and hence low and poorly reproducible levels of therapeutic activity. It has now been found that the problem of poor dissolution can be overcome by producing the compounds in the form of a particular class of salts. Furthermore, in selecting compounds for use in therapy it is important to take a number or criteria into account, for example, in addition to physical qualities such as good dissolution (and hence good bioavailability) , the desired level of intrinsic potency and duration of action of the chosen compounds has to be at the desired level.
• strong acid shall be taken to mean an acid with a pka of less than about 4.0.
• the nature of such acids will be apparent to those skilled in the art and include, for example, mineral acids such as hydrochloric acid, and sulphonic acids such as alkyl sulphonic acids, in particular methane sulphonic acid.
• Particularly preferred salts of the present invention are those formed by reaction with hydrochloric acid or methane sulphonic acid, that is to say,
• the salts of the present invention have been found to exhibit exceptionally fast intrinsic dissolution rates when compared to the free base compound of structure (I) disclosed in EP-330485-A.
• the free base has a poor dissolution rate and, as such, may be expected in vivo to exhibit poorly reproducible bioavailability (and so be less effective therapeutically)
• the salts of the present invention are expected to exhibit a much more consistent bioavailability (since their dissolution rates are far more favourable) and to prove more effective per given dose and more reliably effective per given dose on administration to patients.
• the salts described herein can be used in therapy in the treatment of gastrointestinal diseases in mammals, in particular humans. Such diseases include, for example, gastric and duodenal ulcers, aspiration pneumonitis and Zollinger-Ellison syndrome. Further, the salts can be used in the treatment of other disorders where an anti-secretory effect is desirable, for example in patients with a history of chronic and excessive alcohol consumption, and in patients with gastrooesophageal reflux disease (GERD) .
• GSD gastrooesophageal reflux disease
• the salts can be administered in a standard pharmaceutical composition comprising the salt and a pharmaceutically acceptable carrier.
• the present invention provides in a further aspect therefore a pharmaceutical composition comprising a salt as described herein in association with a pharmaceutically acceptable carrier.
• Suitable pharmaceutical compositions are as described in EP-330485-A.
• Suitable daily dosage regimens for an adult patient may be, for example, an oral dose of between 1 and 1000 mg, preferably between 1 and 500 mg, or an intravenous, subcutaneous or intramuscular dose of between 0.1 and 100 mg, preferably between 0.1 and 25 mg of the salts described herein, the salt being administered in a unit dosage 1 to 4 times a day.
• the salts can be co-administered with further active ingredients such as antacids (for example, magnesium carbonate or hydroxide and aluminium hydroxide) , non-steroidal anti-inflammatory drugs, steroids or nitrite scavengers or other drugs used for treating gastric ulcers (for example, prostanoids or H 2 -antagonists such as cimetidine) .
• antacids for example, magnesium carbonate or hydroxide and aluminium hydroxide
• non-steroidal anti-inflammatory drugs for example, steroids or nitrite scavengers or other drugs used for treating gastric ulcers (for example, prostanoids or H 2 -antagonists such as cimetidine) .
• active ingredients such as antacids (for example, magnesium carbonate or hydroxide and aluminium hydroxide) , non-steroidal anti-inflammatory drugs, steroids or nitrite scavengers or other drugs used for treating gastric ulcers (for example, prostanoids or H 2

Applications Claiming Priority (4)

Publications (1)

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• 1992
  • 1992-01-27 MA MA22687A patent/MA22401A1/fr unknown
  • 1992-01-27 HU HU9302201A patent/HUT67609A/hu unknown
  • 1992-01-27 EP EP92903019A patent/EP0569396A1/en not_active Withdrawn
  • 1992-01-27 CZ CZ931532A patent/CZ153293A3/cs unknown
  • 1992-01-27 AP APAP/P/1992/000352A patent/AP337A/en active
  • 1992-01-27 SK SK709-93A patent/SK70993A3/sk unknown
  • 1992-01-27 AU AU11799/92A patent/AU652028B2/en not_active Ceased
  • 1992-01-27 WO PCT/EP1992/000200 patent/WO1992012969A1/en not_active Application Discontinuation
  • 1992-01-27 MX MX9200338A patent/MX9200338A/es unknown
  • 1992-01-27 CA CA002099117A patent/CA2099117A1/en not_active Abandoned
  • 1992-01-27 JP JP4503051A patent/JPH06504541A/ja active Pending
  • 1992-01-27 NZ NZ241408A patent/NZ241408A/en unknown
  • 1992-01-28 IL IL100791A patent/IL100791A0/xx unknown
  • 1992-01-28 IE IE026792A patent/IE920267A1/en unknown
  • 1992-01-28 PT PT100056A patent/PT100056A/pt not_active Application Discontinuation
  • 1992-01-28 CN CN92101029A patent/CN1064268A/zh active Pending
• 1993
  • 1993-07-28 FI FI933376A patent/FI933376A/fi unknown
  • 1993-07-28 NO NO932722A patent/NO932722D0/no unknown

Non-Patent Citations (1)

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