Novel compounds

Abstract

Novel substituted 1,5,7-trisubstituted-3,4-dihydro-pyrimido[4,5-d]pyrimidin-2-(1H)-one compounds and compositions, and their use in therapy as CSBP/RK/p38 kinase inhibitors.

1 . The compound which is 3-[2-{[3-(diethylamino)propyl]amino}-8-(2,6-difluorophenyl)-7-oxo-5,6,7,8-tetrahydropyrimido[4,5-d]pyrimidin-4-yl]-4-methyl-N-propylbenzamide, or a pharmaceutically acceptable salt thereof. 
   
   
       2 . The compound according to  claim 1  which is:
 3-[2-{[3-(diethylamino)propyl]amino}-8-(2,6-difluorophenyl)-7-oxo-5,6,7,8-tetrahydropyrimido[4,5-d]pyrimidin-4-yl]-4-methyl-N-propylbenzamide hydrochloride;   3-[2-{[3-(diethylamino)propyl]amino}-8-(2,6-difluorophenyl)-7-oxo-5,6,7,8-tetrahydropyrimido[4,5-d]pyrimidin-4-yl]-4-methyl-N-propylbenzamide hemisulfate;   3-[2-{[3-(diethylamino)propyl]amino}-8-(2,6-difluorophenyl)-7-oxo-5,6,7,8-tetrahydropyrimido[4,5-d]pyrimidin-4-yl]-4-methyl-N-propylbenzamide fumarate;   3-[2-{[3-(diethylamino)propyl]amino}-8-(2,6-difluorophenyl)-7-oxo-5,6,7,8-tetrahydropyrimido[4,5-d]pyrimidin-4-yl]-4-methyl-N-propylbenzamide phosphate;   3-[2-{[3-(diethylamino)-propyl]amino}-8-(2,6-difluorophenyl)-7-oxo-5,6,7,8-tetrahydropyrimido[4,5-d]pyrimidin-4-yl]-4-methyl-N-propylbenzamide ethanedisulfonate; or   3-[2-{[3-(diethylamino)propyl]amino}-8-(2,6-difluorophenyl)-7-oxo-5,6,7,8-tetrahydropyrimido[4,5-d]pyrimidin-4-yl]-4-methyl-N-propylbenzamide.   
   
   
       3 . The compound according to  claim 1  wherein the pharmaceutically acceptable salt is selected from the group consisting of acetate, benzenesulfonate, benzoate, bicarbonate, bisulfate, bitartrate, borate, bromide, calcium edetate, camsylate, carbonate, chloride, clavulanate, citrate, dihydrochloride, edetate, edisylate, estolate, esylate, ethanesulphonate, formate, fumarate, gluceptate, gluconate, glutamate, glycollylarsanilate, hexylresorcinate, hydrabamine, hydrobromide, hydrochloride, hydrogen phosphate, hydroiodide, hydroxynaphthoate, iodide, isethionate, lactate, lactobionate, laurate, malate, maleate, mandelate, mesylate, methylbromide, methylnitrate, methylsulfate, monopotassium maleate, mucate, napsylate, nitrate, N-methylglucamine, oxalate, oxaloacetate, pamoate (embonate), palmitate, pantothenate, phosphate/diphosphate, piruvate, polygalacturonate, saccharate, salicylate, stearate, subacetate, succinate, sulphate, tannate, tartrate, teoclate, tosylate, triethiodide, trifluoroacetate and valerate. 
   
   
       4 . A pharmaceutical composition comprising a compound according to  claim 1 , or a pharmaceutically acceptable salt thereof, in admixture with one or more pharmaceutically acceptable carriers, diluents or excipients. 
   
   
       5 . A pharmaceutical composition comprising a compound according to  claim 2  in admixture with one or more pharmaceutically acceptable carriers, diluents or excipients. 
   
   
       6 . A pharmaceutical composition comprising a compound according to  claim 3  in admixture with one or more pharmaceutically acceptable carriers, diluents or excipients. 
   
   
       7 . A pharmaceutical composition according to  claim 4  adapted for administration by intranasal or oral inhalation means. 
   
   
       8 . A pharmaceutical composition according to  claim 5  adapted for administration by intranasal or oral inhalation means. 
   
   
       9 . A pharmaceutical composition according to  claim 6  adapted for administration by intranasal or oral inhalation means. 
   
   
       10 . The compound which is 3-[2-{[3-(diethylamino)propyl]amino}-8-(2,6-difluorophenyl)-7-oxo-5,6,7,8-tetrahydropyrimido[4,5-d]pyrimidin-4-yl]-4-methyl-N-propylbenzamide, or a pharmaceutically acceptable salt thereof. 
   
   
       11 . A pharmaceutical composition comprising a compound according to  claim 10  in admixture with one or more pharmaceutically acceptable carriers, diluents or excipients. 
   
   
       12 . A pharmaceutical composition according to  claim 11  adapted for administration by intranasal or oral inhalation means. 
   
   
       13 . The compound 3-[8-(2,6-difluorophenyl)-2-(4-methyl-1,4′-bipiperidin-1′-yl)-7-oxo-5,6,7,8-tetrahydropyrimido[4,5-d]pyrimidin-4-yl]-4-methyl-N-(1-methylethyl)benzamide, or pharmaceutically acceptable salt thereof. 
   
   
       14 . The compound according to  claim 13  wherein the pharmaceutically acceptable salt is selected from the group consisting of acetate, benzenesulfonate, benzoate, bicarbonate, bisulfate, bitartrate, borate, bromide, calcium edetate, camsylate, carbonate, chloride, clavulanate, citrate, dihydrochloride, edetate, edisylate, estolate, esylate, ethanesulphonate, formate, fumarate, gluceptate, gluconate, glutamate, glycollylarsanilate, hexylresorcinate, hydrabamine, hydrobromide, hydrochloride, hydrogen phosphate, hydroiodide, hydroxynaphthoate, iodide, isethionate, lactate, lactobionate, laurate, malate, maleate, mandelate, mesylate, methylbromide, methylnitrate, methylsulfate, monopotassium maleate, mucate, napsylate, nitrate, N-methylglucamine, oxalate, oxaloacetate, pamoate (embonate), palmitate, pantothenate, phosphate/diphosphate, piruvate, polygalacturonate, saccharate, salicylate, stearate, subacetate, succinate, sulphate, tannate, tartrate, teoclate, tosylate, triethiodide, trifluoroacetate and valerate. 
   
   
       15 . A pharmaceutical composition comprising a compound according to  claim 13 , or a pharmaceutically acceptable salt thereof, in admixture with one or more pharmaceutically acceptable carriers, diluents or excipients. 
   
   
       16 . A pharmaceutical composition comprising a compound according to  claim 14  in admixture with one or more pharmaceutically acceptable carriers, diluents or excipients. 
   
   
       17 . A pharmaceutical composition according to  claim 15  adapted for administration by intranasal or oral inhalation means. 
   
   
       18 . A pharmaceutical composition according to  claim 16  adapted for administration by intranasal or oral inhalation means. 
   
   
       19 . The compound 3-[8-(2,6-difluorophenyl)-2-(4-methyl-1,4′-bipiperidin-1′-yl)-7-oxo-5,6,7,8-tetrahydropyrimido[4,5-d]pyrimidin-4-yl]-4-methyl-N-(1-methylethyl)benzamide. 
   
   
       20 . A pharmaceutical composition comprising a compound according to  claim 19  in admixture with one or more pharmaceutically acceptable carriers, diluents or excipients. 
   
   
       21 . A pharmaceutical composition according to  claim 20  adapted for administration by intranasal or oral inhalation means.