beta3- adrenergic receptor agonist crystal forms, processes for the production thereof, and uses thereof

A crystal form of (R)-2-(2-(4-oxazol-4-yl-phenoxy)-ethylamino)-1-pyridin-3-yl-ethanol), p-toluenesulfonate salt, monohydrate.

A process for preparing crystalline (R)-2-(2-(4-oxazol-4-yl-phenoxy)-ethylamino)-1-pyridin-3-yl-ethanol), p-toluenesulfonate salt comprising the steps of:

• (a) preparing a solution of (R)-2-(2-(4-oxazol-4-yl-phenoxy)-ethylamino)-1-pyridin-3-yl-ethanol in a reaction-inert solvent;
• and
• (b) treating said solution from step (a) with p-toluenesulfonic acid monohydrate to obtain a final stoichiometric ratio of (R)-2-(2-(4-oxazol-4-yl-phenoxy)-ethylamino)-1-pyridin-3-yl-ethanol to p-toluenesulfonic acid monohydrate of about 1:1.

A process for preparing crystalline (R)-2-(2-(4-oxazol-4-yl-phenoxy)-ethylamino)-1-pyridin-3-yl-ethanol), p-toluenesulfonate salt, monohydrate comprising the step of contacting (R)-2-(2-(4-oxazol-4-yl-phenoxy)-ethylamino)-1-pyridin-3-yl-ethanol), p-toluenesulfonate salt with water, optionally in the presence of a reaction-inert solvent.

A pharmaceutical composition comprising

• (i) a therapeutically effective amount of a crystal form of (R)-2-(2-(4-oxazol-4-yl-phenoxy)-ethylamino)-1-pyridin-3-yl-ethanol), p-toluenesulfonate salt, or a crystal form of (R)-2-(2-(4-oxazol-4-yl-phenoxy)-ethylamino)-1-pyridin-3-yl-ethanol), p-toluenesulfonate salt, monohydrate;
• and
• (ii) a pharmaceutically acceptable carrier, vehicle, or diluent.

A method of treating a β3-adrenergic receptor-mediated disease, condition, or disorder comprising the step of administering to a mammal in need of such treatment a therapeutically effective amount of a crystal form of (R)-2-(2-(4-oxazol-4-yl-phenoxy)-ethylamino)-1-pyridin-3-yl-ethanol), p-toluenesulfonate salt;

• a crystal form of (R)-2-(2-(4-oxazol-4-yl-phenoxy)-ethylamino)-1-pyridin-3-yl-ethanol), p-toluenesulfonate salt, monohydrate;
• or a pharmaceutical composition comprising said a crystal form of (R)-2-(2-(4-oxazol-4-yl-phenoxy)-ethylamino)-1-pyridin-3-yl-ethanol), p-toluenesulfonate salt, or said crystal form of (R)-2-(2-(4-oxazol-4-yl-phenoxy)-ethylamino)-1-pyridin-3-yl-ethanol), p-toluenesulfonate salt, monohydrate.

A method of increasing lean meat content of an edible animal comprising the step of administering to said edible animal a lean meat increasing amount of a crystal form of (R)-2-(2-(4-oxazol-4-yl-phenoxy)-ethylamino)-1-pyridin-3-yl-ethanol), p-toluenesulfonate salt;

• a crystal form of (R)-2-(2-(4-oxazol-4-yl-phenoxy)-ethylamino)-1-pyridin-3-yl-ethanol), p-toluenesulfonate salt, monohydrate;
• or a pharmaceutical composition comprising said crystal form of (R)-2-(2-(4-oxazol-4-yl-phenoxy)-ethylamino)-1-pyridin-3-yl-ethanol), p-toluenesulfonate salt, or said crystal form of (R)-2-(2-(4-oxazol-4-yl-phenoxy)-ethylamino)-1-pyridin-3-yl-ethanol), p-toluenesulfonate salt, monohydrate.