4-(2,6-dichloro-benzoylamino)-1H-pyrazole-3-carboxylic acid piperidin-4-ylamide acid addition salts as kinase inhibitors
AssigneeAstex Therapeutics Limited
InventorsPaul Graham Wyatt, David Charles Rees, Mladen Vinkovic, Gary Trewartha
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Abstract
The invention provides an acid addition salt of 4-(2,6-dichloro-benzoylamino)-1H-pyrazole-3-carboxylic acid piperidin-4-ylamide and crystals thereof, the salt being formed with an acid selected from methanesulphonic acid and acetic acid and mixtures thereof. Also provided are the novel uses of salts of 4-(2,6-dichloro-benzoylamino)-1H-pyrazole-3-carboxylic acid piperidin-4-ylamide, processes for the preparation of 4-(2,6-dichloro-benzoylamino)-1H-pyrazole-3-carboxylic acid piperidin-4-ylamide and its salts and novel chemical intermediates.
Claims22
An acid addition salt of 4-(2,6-dichloro-benzoylamino)-1H-pyrazole-3-carboxylic acid piperidin-4-ylamide, wherein said salt is chosen from a methanesulphonate salt, an acetate salt and mixtures thereof.
A pharmaceutical composition comprising a salt of 4-(2,6-dichloro-benzoylamino)-1H-pyrazole-3-carboxylic acid piperidin-4-ylamide, wherein said salt is chosen from a methanesulphonate salt, an acetate salt and mixtures thereof, and a pharmaceutically acceptable carrier.
A process for preparing an acid addition salt of 4-(2,6-dichloro-benzoylamino)-1H-pyrazole-3-carboxylic acid piperidin-4-ylamide, wherein said salt is chosen from a methanesulphonate salt, an acetate salt and mixtures thereof, which process comprises reacting a compound of the formula (XI):
- with a compound of the formula (XII):
- where PG is an amine-protecting group, in an organic solvent in the presence of a non-interfering base, to give a compound of the formula (XIII):
- and thereafter removing the protecting group PG to give 4-(2,6-dichloro-benzoylamino)-1H-pyrazole-3-carboxylic acid piperidin-4-ylamide or salt thereof;
- and optionally recrystallizing a salt thus formed to give a crystalline form.
A compound of formula (XI):
A method for treating B-cell lymphoma and chronic lymphocytic leukemia, which method comprises administering to a mammal in need thereof a salt of 4-(2,6-dichloro-benzoylamino_-1H-pyrazole-3-carboxylic acid piperidin-4-ylamide, wherein said salt is chosen from methanesulphonatesalt, an acetate salt and mixtures thereof, in an amount effective in inhibiting abnormal cell growth.
A method for treating chronic lymphocytic leukemia comprising administering a compound of formula (Va):
- or salts or tautomers or N-oxides thereof;
- wherein
- R2 is hydrogen or methyl;
- R11 is hydrogen or C1-3 alkyl;
- r is 0, 1 or 2;
- R14a is hydrogen or methyl;
- R19 is fluorine;
- chlorine;
- C1-4 alkoxy optionally substituted by fluoro or C1-2-alkoxy;
- or C1-4 alkyl optionally substituted by fluoro or C1-2-alkoxy;
- and
- w is 0, 1, 2 or 3.
Dependencies are inferred from the claim text.