Salt Forms of 4- (4-Methylpiperazin-1-Ylmethyl) -N- [4-Methyl-3- (4-Pyridin-3-Yl) Pyrimidin-2-Ylamino) Phenyl]- Benzamide

Abstract

The present invention relates to acid addition salts of 4-[(4-methyl-1-piperazinyl)methyl]-N-(4-methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]phenyl]-benzamide, which are selected from the group consisting of a tartrate salt, such as a (D)(−) tartrate salt or a (L)(+) tartrate salt, a hydrochloride salt, a citrate salt, a malate salt, a fumarate salt, a succinate salt, a benzoate salt, a benzenesulfonate salt, a pamoate salt, a formate salt, a malonate salt, a 1,5-naphthalenedisulfonate salt, a salicylate salt, a cyclohexanesulfamate salt, a lactate salt, a mandelate salt, aq glutarate salt, an adipate salt, a squarate salt, a vanillate salt, an oxaloacetate salt, an ascorbate salt and a sulfate salt.

1 . An acid addition salt of 4-[(4-methyl-1-piperazinyl)methyl]-N-[4-methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]phenyl]-benzamide selected from the group consisting of a tartrate salt, such as a (D)(−) tartrate salt or a (L)(+) tartrate salt, a hydrochloride salt, a citrate salt, a malate salt, particularly a D-malate salt, a fumarate salt, a succinate salt, a benzoate salt, a benzenesulfonate salt, a pamoate salt, a formate salt, a malonate salt, a 1,5-naphthalenedisulfonate salt, a salicylate salt, a cyclohexanesulfamate salt, a lactate salt, particularly a (S)-lactate salt, a mandelate salt, particularly an (R)(−) mandelate salt, aq glutarate salt, an adipate salt, a squarate salt, a vanillate salt, an oxaloacetate salt, an ascorbate salt, particularly an (L)-ascorbate salt and a sulfate salt. 
     
     
         2 . An acid addition salt selected from the group consisting of imatinib ascorbate, imatinib formate, imatinib malonate, imatinib oxaloacetate, imatinib squarate and imatinib vanillate. 
     
     
         3 . An acid addition salt of 4-[(4-methyl-1-piperazinyl)methyl]-N-[4-methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]phenyl]-benzamide selected from the group consisting of a tartrate salt, such as a (D)(−) tartrate salt or a (L)(+) tartrate salt, a hydrochloride salt, a citrate salt, a malate salt, particularly a D-malate salt, a fumarate salt, a succinate salt, a benzoate salt, a benzenesulfonate salt, a pamoate salt, a hemiformate salt, a malonate salt, a salicylate salt, a cyclohexanesulfamate salt, a mandelate salt, particularly an (R)(−) mandelate salt, a hemiglutarate salt, an adipate salt, a vanillate salt and a sulfate salt. 
     
     
         4 . An acid addition salt selected from the group consisting of imatinib D-tartrate, imatinib D-malate, imatinib hemiformate, imatinib malonate, imatinib salicylate, imatinib hemiglutamate, imatinib cyclohexanesulfamate, imatinib mandelate, particularly imatinib (R)(−) mandelate, imatinib adipate, imatinib vanillate and imatinib sulfate. 
     
     
         5 . A pharmaceutical composition which comprises a pharmaceutically acceptable carrier and an acid addition salt of 4-[(4-methyl-1-piperazinyl)methyl]-N-[4-methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]phenyl]-benzamide selected from the group consisting of a tartrate salt, such as a (D)(−) tartrate salt or a (L)(+) tartrate salt, a hydrochloride salt, a citrate salt, a malate salt, particularly a D-malate salt, a fumarate salt, a succinate salt, a benzoate salt, a benzenesulfonate salt, a pamoate salt, a formate salt, a malonate salt, a 1,5-naphthalenedisulfonate salt, a salicylate salt, a cyclohexanesulfamate salt, a lactate salt, particularly a (S)-lactate salt, a mandelate salt, particularly an (R)(−) mandelate salt, aq glutarate salt, an adipate salt, a squarate salt, a vanillate salt, an oxaloacetate salt, an ascorbate salt, particularly an (L)-ascorbate salt and a sulfate salt. 
     
     
         6 . A pharmaceutical composition of  claim 3  wherein the acid addition salt is selected from the group consisting of imatinib ascorbate, imatinib formate, imatinib malonate, imatinib oxaloacetate, imatinib squarate and imatinib vanillate. 
     
     
         7 . Use of an acid addition salt of 4-[(4-methyl-1-piperazinyl)methyl]-N-[4-methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]phenyl]-benzamide according to  claim 1  for the manufacture of a pharmaceutical composition for the treatment of a tumour disease, especially the treatment of leukemia.