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WO1996005199A1 - Sel d'imidazopyridine - Google Patents

Sel d'imidazopyridine Download PDF

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Publication number
WO1996005199A1
WO1996005199A1 PCT/EP1995/003139 EP9503139W WO9605199A1 WO 1996005199 A1 WO1996005199 A1 WO 1996005199A1 EP 9503139 W EP9503139 W EP 9503139W WO 9605199 A1 WO9605199 A1 WO 9605199A1
Authority
WO
WIPO (PCT)
Prior art keywords
compound according
salt
compound
methoxycarbonylamino
dimethylimidazo
Prior art date
Application number
PCT/EP1995/003139
Other languages
German (de)
English (en)
Inventor
Georg Rainer
Jörg Senn-Bilfinger
Gerhard Grundler
Richard Riedel
Stefan Postius
Wolfgang-Alexander Simon
Original Assignee
Byk Gulden Lomberg Chemische Fabrik Gmbh
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Byk Gulden Lomberg Chemische Fabrik Gmbh filed Critical Byk Gulden Lomberg Chemische Fabrik Gmbh
Priority to AU33432/95A priority Critical patent/AU3343295A/en
Publication of WO1996005199A1 publication Critical patent/WO1996005199A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems

Definitions

  • the invention relates to a new imidazopyridine salt which is used in the pharmaceutical industry as an active ingredient for the production of pharmaceuticals.
  • European patent application EP-A-0033 094 describes imidazo [1,2-a] pyridines which bear an aryl substituent in the 8-position, which is preferably a phenyl, thienyl, pyridyl or chlorine or fluorine group , Methyl, tert-butyl, trifluoromethyl, ethoxy or cyano substituted phenyl radical.
  • aryl radicals in EP-A-0033 094 are the phenyl, o- or p-fluorophenyl, p-chlorophenyl and 2,4,6-trimethylphenyl radicals, of which the phenyl, o- or p-fluorophenyl radicals and 2,4,6-tri ethylphenyl are particularly preferred.
  • EP-A-0 204 285 EP-A-0 228006, EP-A-0 268989 and EP-A-0308917 imidazo [1,2-a] pyridines are described which are described in 3- Position carry an unsaturated aliphatic radical, in particular a (substituted) alkynyl radical.
  • European patent application EP-A-0 266890 describes imidazo [1,2-a] pyridines which are substituted in the 8-position by an alkenyl, alkyl or cycloalkylalkyl radical.
  • the invention relates to the salt of the compound 8- (2-methoxycarbonylamino-6-methylbenzylamino) -2,3-dimethylimidazo [1,2-a] pyridine with D, L-apple acid, ie the 8- (2- Methoxycarbonylamino-6-methylbenzylamino) -2,3-dimethylimidazo [1,2-a] pyridine-D, L-hemimalate and its enantiomers.
  • the 8- (2-methoxycarbonylamino-6-methylbenzylamino) -2,3-dimethylimidazo [1,2-a] pyridine can be prepared as described in the examples below.
  • the preparation of the malate is also described in the examples.
  • RT room temperature
  • h hour (s)
  • min minute (s)
  • mp melting point
  • dec. decomposition
  • the compound is known from EP-A-0 299470 or it can be prepared analogously to that described there.
  • the 8- (2-methoxycarbonylamino-6-methylbenzylamino) -2,3-dimethylimidazo [1,2-a] pyridine-D, L-hemimalate has valuable pharmacological properties which make it commercially usable. In particular, it has a pronounced inhibition of gastric acid secretion and an excellent gastric and intestinal protective action in warm-blooded animals.
  • the compound according to the invention is distinguished by a high selectivity of action, a comparatively long duration of action, good enteral effectiveness, the absence of essential side effects, a large therapeutic breadth and, in particular, excellent bioavailability.
  • “Stomach and intestinal protection” in this context means the prevention and treatment of gastrointestinal diseases, in particular gastrointestinal inflammatory diseases and lesions (such as, for example, ulcer ventriculi, duodenal ulcer, gastritis, hyperacid or drug-induced irritable stomach), which are caused, for example, by microorganisms (eg Helicobacter pylori), bacterial toxins, medications (eg certain anti-inflammatory drugs and anti-rheumatic drugs), chemicals (eg ethanol), gastric acid or stressful situations.
  • the compound according to the invention also has an intrinsic effect against the Helicobacter pylori germ.
  • the compound according to the invention surprisingly proves to be clearly superior to the compounds known from the prior art on various models in which the antiulcerogenic and the antisecretory properties are determined.
  • the compound according to the invention is outstandingly suitable for use in human and veterinary medicine, it being used in particular for the treatment and / or prophylaxis of diseases of the stomach and / or intestine.
  • the invention therefore furthermore relates to the compound according to the invention for use in the treatment and / or prophylaxis of the abovementioned diseases.
  • the invention also encompasses the use of the compound according to the invention for the production of medicaments which are used for the treatment and / or prophylaxis of the abovementioned diseases.
  • the invention further comprises the use of the compound according to the invention for the treatment and / or prophylaxis of the abovementioned diseases.
  • the invention further relates to medicaments which contain the compound according to the invention.
  • the pharmaceuticals are produced by methods known per se and familiar to the person skilled in the art.
  • suitable pharmaceutical auxiliaries or carriers in the form of tablets, dragées, capsules, suppositories, plasters (for example as TTS), emulsions Sions, suspensions or solutions are used, the active ingredient content advantageously being between 0.1 and 95% and the galenic dosage form being precisely adapted to the active ingredient and / or the desired
  • auxiliaries and excipients suitable for the desired pharmaceutical formulations on the basis of his specialist knowledge.
  • active ingredient carriers for example antioxidants, dispersants, emulsifiers, defoamers, taste correctives, preservatives, solubilizers, dyes or in particular permeation promoters and complexing agents (e.g. cyclodextrins) can be used.
  • the active ingredients can be administered orally, parenterally or percutaneously.
  • the active ingredient in general, it has proven to be advantageous in human medicine for the active ingredient to be administered orally in a daily dose of about 0.01 to about 20, preferably 0.05 to 5, in particular 0.1 to 1.5 mg / kg of body weight, optionally in the form of several, preferably 1 to 4, individual doses to achieve the desired result.
  • a daily dose of about 0.01 to about 20, preferably 0.05 to 5, in particular 0.1 to 1.5 mg / kg of body weight, optionally in the form of several, preferably 1 to 4, individual doses to achieve the desired result.
  • similar or generally lower doses in particular when the active ingredient is administered intravenously
  • the optimum dosage and type of application of the active ingredient required in each case can easily be determined by any person skilled in the art on the basis of his specialist knowledge.
  • the pharmaceutical preparations can also contain one or more pharmacologically active constituents of other groups of medicaments, such as antacids, for example aluminum hydroxide, magnesium aluminate; Tranquilizers, such as benzodiazepines, for example diazepam; Spasmolytics, e.g. Bietamiverin, Camylofin, Anticholinergica, e.g. Oxyphencyclimine, phencarbamide; Local anesthetics, e.g. Tetracaine, procaine; optionally also contain ferments, vitamins or amino acids.
  • antacids for example aluminum hydroxide, magnesium aluminate
  • Tranquilizers such as benzodiazepines, for example diazepam
  • Spasmolytics e.g. Bietamiverin, Camylofin, Anticholinergica, e.g. Oxyphencyclimine, phencarbamide
  • Local anesthetics e.
  • the combination of the compound according to the invention with pharmaceuticals which inhibit acid secretion should be emphasized in particular So-called peripheral anticholinergics (eg pirenzepin, telenzepin) and with gastrin antagonists with the aim of strengthening the main effect in an additive or superadditive sense and / or eliminating or reducing the side effects, or further the combination with antibacterially active substances ⁇ zen (such as cephalosporins, tetracyclines, nalidixic acid, penicillins or bismuth salts) to combat Helicobacter pylori. pharmacology
  • H blockers for example ci-etidine, ranitidine
  • H / K -ATPase inhibitors for example omeprazole, pantoprazole
  • gastrin antagonists with the aim of strengthening the main effect in an additive or superadditive sense and / or eliminating or reducing the side effects
  • antibacterially active substances ⁇ zen such as cephalosporins, tetracyclines
  • Table 1 below shows the influence of the compound according to the invention after intraduodenal administration on the acid secretion of the perfused rat stomach stimulated by pentagastrin in vivo.
  • anesthetized rats (CD rat, female, 200-250 g * 1.5 g / kg in urethane) were opened with a median upper abdominal incision and a PVC catheter transorally in the esophagus and another one after tracheotomy fixed via the pylorus in such a way that the tube ends just protruded into the stomach lumen.
  • the catheter leading out of the pylorus led outwards through a lateral opening in the right abdominal wall.
  • the body temperature of the animals was kept at a constant 37.8-38 ° C. by means of infrared radiation and heating pads (automatic, stepless regulation via rectal temperature sensors).

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne le composé 8-(2-méthoxycarbonylamino-6-méthylbenzylamino)-2,3-diméthylimidazo-[1,2-a]pyridine-D,L-hémimalate et son utilisation thérapeutique.
PCT/EP1995/003139 1994-08-12 1995-08-08 Sel d'imidazopyridine WO1996005199A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU33432/95A AU3343295A (en) 1994-08-12 1995-08-08 Imidazopyridine salt

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CH249994 1994-08-12
CH2499/94-7 1994-08-12

Publications (1)

Publication Number Publication Date
WO1996005199A1 true WO1996005199A1 (fr) 1996-02-22

Family

ID=4235181

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1995/003139 WO1996005199A1 (fr) 1994-08-12 1995-08-08 Sel d'imidazopyridine

Country Status (2)

Country Link
AU (1) AU3343295A (fr)
WO (1) WO1996005199A1 (fr)

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007115305A2 (fr) 2006-04-04 2007-10-11 Cogentus Pharmaceuticals, Inc. Formes de dosage orales incluant un inhibiteur de l'agrégation plaquettaire et un inhibiteur acide
WO2009105568A1 (fr) 2008-02-20 2009-08-27 The Curators Of The University Of Missouri Composition comprenant une combinaison d'oméprazole et de lansoprazole, et un agent tampon, et ses méthodes d'utilisation
EP2486910A2 (fr) 2006-10-27 2012-08-15 The Curators Of The University Of Missouri Appareil comprenant plusieurs chambres et une tête de distribution
US8852636B2 (en) 2001-06-01 2014-10-07 Pozen Inc. Pharmaceutical compositions for the coordinated delivery of NSAIDs
US8945621B2 (en) 2009-06-25 2015-02-03 Pozen Inc. Method for treating a patient at risk for developing an NSAID-associated ulcer
US9220698B2 (en) 2008-09-09 2015-12-29 Pozen Inc. Method for delivering a pharmaceutical composition to patient in need thereof
US9539214B2 (en) 2011-12-28 2017-01-10 Pozen Inc. Compositions and methods for delivery of omeprazole plus acetylsalicylic acid
WO2018209150A1 (fr) 2017-05-10 2018-11-15 Axsome Therapeutics, Inc. Compositions pharmaceutiques contenant du méloxicam
EP3789016A1 (fr) 2017-01-04 2021-03-10 Axsome Therapeutics, Inc. Compositions pharmaceutiques contenant du méloxicam et du rizatriptan
EP4008319A1 (fr) 2015-11-25 2022-06-08 Axsome Therapeutics, Inc. Compositions pharmaceutiques contenant du méloxicam

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0033094A1 (fr) * 1980-01-23 1981-08-05 Schering Corporation Imidazo (1,2-a) pyridines, procédés pour leur préparation et compositions pharmaceutiques les contenant
WO1994018199A1 (fr) * 1993-02-15 1994-08-18 Byk Gulden Lomberg Chemische Fabrik Gmbh Imidazopyridines et leur utilisation pour traiter des maladies gastro-intestinales

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0033094A1 (fr) * 1980-01-23 1981-08-05 Schering Corporation Imidazo (1,2-a) pyridines, procédés pour leur préparation et compositions pharmaceutiques les contenant
WO1994018199A1 (fr) * 1993-02-15 1994-08-18 Byk Gulden Lomberg Chemische Fabrik Gmbh Imidazopyridines et leur utilisation pour traiter des maladies gastro-intestinales

Cited By (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9345695B2 (en) 2001-06-01 2016-05-24 Pozen Inc. Pharmaceutical compositions for the coordinated delivery of NSAIDs
US9707181B2 (en) 2001-06-01 2017-07-18 Pozen Inc. Pharmaceutical compositions for the coordinated delivery of NSAIDs
US8852636B2 (en) 2001-06-01 2014-10-07 Pozen Inc. Pharmaceutical compositions for the coordinated delivery of NSAIDs
US8858996B2 (en) 2001-06-01 2014-10-14 Pozen Inc. Pharmaceutical compositions for the coordinated delivery of NSAIDS
US8865190B2 (en) 2001-06-01 2014-10-21 Pozen Inc. Pharmaceutical compositions for the coordinated delivery of NSAIDs
US9161920B2 (en) 2001-06-01 2015-10-20 Pozen Inc. Pharmaceutical compositions for the coordinated delivery of NSAIDs
US9364439B2 (en) 2001-06-01 2016-06-14 Pozen Inc. Pharmaceutical compositions for the coordinated delivery of NSAIDs
US9198888B2 (en) 2001-06-01 2015-12-01 Pozen Inc. Pharmaceutical compositions for the coordinated delivery of NSAIDs
WO2007115305A2 (fr) 2006-04-04 2007-10-11 Cogentus Pharmaceuticals, Inc. Formes de dosage orales incluant un inhibiteur de l'agrégation plaquettaire et un inhibiteur acide
EP2486910A2 (fr) 2006-10-27 2012-08-15 The Curators Of The University Of Missouri Appareil comprenant plusieurs chambres et une tête de distribution
WO2009105568A1 (fr) 2008-02-20 2009-08-27 The Curators Of The University Of Missouri Composition comprenant une combinaison d'oméprazole et de lansoprazole, et un agent tampon, et ses méthodes d'utilisation
US9220698B2 (en) 2008-09-09 2015-12-29 Pozen Inc. Method for delivering a pharmaceutical composition to patient in need thereof
US9393208B2 (en) 2008-09-09 2016-07-19 Pozen Inc. Method for delivering a pharmaceutical composition to patient in need thereof
US9801824B2 (en) 2008-09-09 2017-10-31 Pozen Inc. Method for delivering a pharmaceutical composition to patient in need thereof
US8945621B2 (en) 2009-06-25 2015-02-03 Pozen Inc. Method for treating a patient at risk for developing an NSAID-associated ulcer
US9539214B2 (en) 2011-12-28 2017-01-10 Pozen Inc. Compositions and methods for delivery of omeprazole plus acetylsalicylic acid
US9987231B2 (en) 2011-12-28 2018-06-05 Pozen Inc. Compositions and methods for delivery of omeprazole plus acetylsalicylic acid
US10603283B2 (en) 2011-12-28 2020-03-31 Genus Lifesciences, Inc. Compositions and methods for delivery of omeprazole plus acetylsalicylic acid
EP4008319A1 (fr) 2015-11-25 2022-06-08 Axsome Therapeutics, Inc. Compositions pharmaceutiques contenant du méloxicam
EP4470614A2 (fr) 2015-11-25 2024-12-04 Axsome Therapeutics, Inc. Compositions pharmaceutiques comprenant du méloxicam
EP3789016A1 (fr) 2017-01-04 2021-03-10 Axsome Therapeutics, Inc. Compositions pharmaceutiques contenant du méloxicam et du rizatriptan
WO2018209150A1 (fr) 2017-05-10 2018-11-15 Axsome Therapeutics, Inc. Compositions pharmaceutiques contenant du méloxicam
EP4467600A2 (fr) 2017-05-10 2024-11-27 Axsome Therapeutics, Inc. Compositions pharmaceutiques comprenant du méloxicam

Also Published As

Publication number Publication date
AU3343295A (en) 1996-03-07

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