Mirabegron

Mirabegron is a selective β3-adrenoceptor agonist with EC50 of 22.4 nM.

Mirabegron is a monocarboxylic acid amide obtained by formal condensation of the carboxy group of 2-amino-1,3-thiazol-4-ylacetic acid with the anilino group of (1R)-2-{[2-(4-aminophenyl)ethyl]amino}-1-phenylethanol. Used for the treatment of overactive bladder syndrome. It has a role as a beta-adrenergic agonist. It is a member of 1,3-thiazoles, an aromatic amide, a member of ethanolamines and a monocarboxylic acid amide.|Mirabegron is a beta-3 adrenergic receptor agonist for the management of overactive bladder. It is an alternative to antimuscarinic drugs for this indication. FDA approved on June 28, 2012.|Mirabegron is a beta3-Adrenergic Agonist. The mechanism of action of mirabegron is as an Adrenergic beta3-Agonist, and Cytochrome P450 2D6 Inhibitor, and Cytochrome P450 3A Inhibitor, and P-Glycoprotein Inhibitor.|Mirabegron is a beta-3 adrenergic agonist that is used for treatment of overactive bladder syndrome. Mirabegron has not been implicated in causing liver enzyme elevations or clinically apparent acute liver injury.|Mirabegron is an orally bioavailable agonist of the human beta-3 adrenergic receptor (ADRB3), with muscle relaxing, neuroprotective and potential antineoplastic activities. Upon oral administration, mirabegron binds to and activates ADRB3, which leads to smooth muscle relaxation. Mirabegron also restores sympathetic stimulation in mesenchymal stem cell (MSC) niches, inhibits JAK2-mutated hematopoietic stem cell (HSC) expansion and blocks the progression of myeloproliferative neoplasms (MPNs). Lack of sympathetic stimulation of the MSC and HSC niche is associated with the development of MPNs.

5 g of the amorphous form of Mirabegron free base prepared in the Preparation Example was dissolved in 50 ml of methanol at room temperature. Then, 1.7 g of L-pyroglutamic acid was dissolved in 17 ml of acetone. The two solvents were mixed and stirred at room temperature for 1 hour. The solvent was then evaporated under reduced pressure using a concentrator to precipitate a solid. 30 ml of ethyl acetate was added to the precipitated solid, and the mixture was stirred at room temperature for 30 minutes. The mixture was filtered under reduced pressure, and vacuum-dried at 45 C for 16 hours to obtain 4.2 g of Mirabegron pidolate.5 g of Amira Begron free base amorphous prepared in the above Preparation Example and 1.5 g of edicylic acid were mixed and then 50 ml of methanol was added. Thereafter, the mixture was stirred at room temperature for 1 hour, filtered under reduced pressure, and vacuum-dried at 45 C for 16 hours to obtain 4.5 g of mirabegron hemicylate.5 g of the amorphous form of Mirabegron free base prepared in the Preparation Example was dissolved in 50 ml of methanol at room temperature. Then, 2.3 g of napadic acid was dissolved in 23 ml of acetone. The two solvents were mixed and stirred at room temperature for 1 hour. The mixture was filtered under reduced pressure, and vacuum-dried at 45 C for 16 hours to obtain 5.8 g of Mirabegron hemipadcylate.10 g of Mirabegron and 100 ml of methanol were added to the reactor, and the temperature was raised to 50 C to completely dissolve the mixture. When dissolution was confirmed, 5.8 g of Myristic acid was added and the mixture was stirred at the same temperature until the reaction was completely dissolved. After complete dissolution, the mixture was stirred at room temperature for 2 hours, and the solvent was removed by concentration under reduced pressure. Then, 100 ml of n-heptane was added to the residue, and the mixture was stirred at room temperature for 12 hours. The resulting solid was filtered, washed with n-heptane (20 ml) and vacuum dried at 40 C to obtain a white14.2 g of Mirabegron myristate was obtained (yield: 89.2%).10 g of Mirabegron and 100 ml of methanol were added to the reactor, and the temperature was raised to 50 C to completely dissolve the mixture. When dissolution was confirmed, 4.6 g of hippuric acid was added and the mixture was stirred at the same temperature until the reaction was completely dissolved. After completely dissolved, the mixture was stirred at room temperature for 2 hours, and then the solvent was removed by concentration under reduced pressure. Then, 100 ml of methyl tert-butyl ether was added to the residue, and the mixture was stirred at room temperature for 12 hours. The resultant solid was filtered, washed with 20 ml of methyl tert-butyl ether, and vacuum dried at 40 C to obtain 13.6 g of white mirabegron hippurate (yield: 93.2%).10 g of Mirabegron and 100 ml of methanol were added to the reactor, and the temperature was raised to 50 C to completely dissolve the mixture. When dissolution was confirmed, 2.9 g of fumaric acid was added and the mixture was stirred at the same temperature until the reaction was completely dissolved. After completely dissolved, the mixture was stirred at room temperature for 2 hours, and then the solvent was removed under reduced pressure. 100 ml of ethyl acetate was added to the residue, and the mixture was stirred at room temperature for 12 hours. The resulting solid was filtered, washed with 20 ml of ethyl acetate, and vacuum dried at 40 to obtain 12.0 g of white mirabegron fumarate (yield 93%).10 g of Mirabegron and 100 ml of methanol were added to the reactor, and the temperature was raised to 50 C to completely dissolve the mixture. When the dissolution was confirmed, 1.4 ml of phosphoric acid was added, and the mixture was stirred at the same temperature until the reaction was completely dissolved. After completely dissolved, the mixture was stirred at room temperature for 2 hours, and then the solvent was removed by concentration under reduced pressure. Then, 100 ml of acetone was added to the residue, and the mixture was stirred at room temperature for 12 hours. The resulting solid was filtered, washed with 20 ml of acetone, and vacuum dried at 40 C to obtain 10.4 g of white mirabegron phosphate (yield: 83.9%).10 g of Mirabegron and 100 ml of methanol were added to the reactor, and the temperature was raised to 50 C to completely dissolve the mixture. When dissolution was confirmed, 4.4 g of orotic acid monohydrate was added and the mixture was stirred at the same temperature until the reaction was completely dissolved. After completely dissolved, the mixture was stirred at room temperature for 2 hours, and then the solvent was removed by concentration under reduced pressure. Then, 100 ml of methyl tert-butyl ether was added to the residue, and the mixture was stirred at room temperature for 12 hours. The resultant solid was filtered, washed with 20 ml of methyl tert-butyl ether, and vacuum dried at 40 C to obtain 11.4 g of white mirabegron orotate (yield: 79.2%).

Potent bladder relaxant and reagent for diabetes remedy.;Labeled Mirabegron, intended for use as an internal standard for the quantification of Mirabegron by GC- or LC-mass spectrometry.

Molecular Weight:396.5
XLogP3:2.1
Hydrogen Bond Donor Count:4
Hydrogen Bond Acceptor Count:6
Rotatable Bond Count:9
Exact Mass:396.16199719
Monoisotopic Mass:396.16199719
Topological Polar Surface Area:129
Heavy Atom Count:28
Complexity:467
Defined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes