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 partly new 3-(lH-tetrazol- -5-yl)-4H-pyrido[l,2-a]pyrimidin-4-ones of the general formula (I) and pharmaceutically acceptable salts and/or hydrates and the preparation thereof. These compounds possess significant antiallergic or antiulcer activity.
• 3-(lH-tetrazol-5-yl)-4H-pyrido[1,2-a]pyrimidin-4- -ones of general formula (I) where R represents hydrogenatom, are described in US-PS Nos. 4122274 and 4209620 as antiallergic agents, whereas in US-PS No. 4457932 as antiulcer agents.
• the basis of our invention is the unexpected dis ⁇ covery that the acrylnitriles of general formula (II) may be transformed in a simple manner, in good yield, and without the formation of by-products into the pyrido- [l,2-a]pyrimidines of general formula (I).
• R stands for hydrogenatom, C 1 _ 4 alkyl group, or c 6 - 10 ar Yl group
• R 1 stands for hydrogenatom, - ⁇ ⁇ _ % alkyl group, halogen- atom, hydroxyl group, nitro group, carboxyl group, C2-5 alkoxycarbonyl group or C ⁇ ⁇ i2 aralkoxy group
• R 2 represents hydrogenatom, C 1 -4 alkyl group, or halogenatom; and a process for the preparation thereof.
• C1--.4 alkyl group means - in itself or in moieties, for instance in alkoxy groups - straight or branched chain aliphatic saturated hydrocarbon groups having one to four carbon atoms (such as e.g. methyl, ethyl, n-propyl and tert.-butyl group).
• C 6 _ ⁇ o aryl group means phenyl group or naphthyl group, optionally bearing a ⁇ - ⁇ alkyl group.
• the present invention also relates to a process for the preparation of compounds of general formula (I) and pharmaceutically acceptable salts and/or hydrates thereof, which comprises cyclising a 3-(2-pyridylamino)- -2-(lH-tetrazol-5-yl)acrylnitrile of general formula (II)
• organic and inorganic acids may be applied. If desired, the reaction may be carried out in the presence of solvent, preferably in the presence of water. As for organic acids alkanecarboxylic acids and arylsulfonic acids may be used. For inorganic acids preferably hydrogenhalides, sulfonic acid and various acids of the phosphor may be applied.
• the reaction may be accomplished, if desired, at elevated temperature. The temperature may be chosen according to the properties of the acidic agent and, if the reaction is carried out in the presence of solvent, according to the properties of the solvent. The reaction is preferably carried out at a temperature different from room temperature.
• the compound of general formula (I) obtained in the reaction precipitates from the reaction mixture after dilution with water or after adjusting the pH of the reaction mixture to neutral and may be recovered for instance by filtration.
• Compounds of general formula (I) may be converted into their pharmaceutically acceptable salts and/or hydrates on the effect of acids or bases. From the salts the bases may be liberated and, if desired, converted into another salt thereof.
• acid addition salts with e.g. hydrochloric acid, hydrobromic acid, sulphuric acid, acetic acid, citric acid ets. may favourably be prepared, as well as the sodium, potassium and calcium salts.
• the compound of general formula (I) or its pharma- ceutically acceptable salts may therapeutically be used in the form of pharmaceutical compositions containing the active ingredient in an admixture with inert non- toxic solid or liquid diluents and carriers.
• compositions may be formulated as solids (tablet, capsule, dragee) or as liquids (solution, suspension, emulsion) .
• the usual materials such as e.g. talc, calcium carbonate, magnesium stearate, water, poly(ethylene glycol) may be used.
• the preparations may contain supplementary materials such as e.g. emulsifying agents, or dissolution materials.
• Example 1 53 . 3 g ( 0. 25 mol) of 3- ( 2-pyridylamino) -2- ( 1H- -tetrazol-5-yl)-acrylnitrile are heated in 500 ml of cone, hydrochloric acid under reflux conditions for 1 hour. After 10-15 mins of heating the original crystals dissolve, and the crystals of the product appear. The resulting suspension is cooled, diluted with 1000 ml of water, and neutralized with 25 % aqueous ammonia solution. The crystals are collected, washed with water.
• Example 5 ⁇ 2.47 g (0.01 mol) of 3-[ (5-chloro-2-pyridyl)- -amino]-2-(lH-tetrazol-5-yl)acrylnitrile are added under stirring to 12 g of polyphosphoric acid at 60 °C.
• the mixture is granulated with the help of 150 g of Endragit-lac solution, then it is dried at 40 °C and re- granulated.
• the granulatum is homogenized with a powder mixture consisting of 20 g of talc and 20 g of magnesium stearate, then in a method known per se, with the help of the appropriate pressure tools, it is pressed into tablets of 50, 100, 200 and 400 mg.

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

Applications Claiming Priority (2)

Publications (1)

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ID=10981335

Family Applications (1)

Country Status (7)

Cited By (17)

Families Citing this family (1)

Citations (1)

• 1992
  • 1992-02-13 HU HU9200432A patent/HUT64064A/hu unknown
• 1993
  • 1993-02-12 MX MX9300779A patent/MX9300779A/es unknown
  • 1993-02-12 IL IL104706A patent/IL104706A0/xx unknown
  • 1993-02-12 AU AU35737/93A patent/AU3573793A/en not_active Withdrawn
  • 1993-02-12 SI SI19939300075A patent/SI9300075A/sl unknown
  • 1993-02-12 WO PCT/HU1993/000009 patent/WO1993016076A1/en active Application Filing
  • 1993-02-13 CN CN93102959.7A patent/CN1080289A/zh active Pending

Patent Citations (1)

Non-Patent Citations (1)

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