JPWO2019178331A5 - - Google Patents

Claims (21)

The compound of the following formula (I), or a pharmaceutically acceptable salt, solvate, coordination complex or prodrug thereof:

In the formula, R ¹ and R ² are selected from C ₁ to C ₆ alkyl, respectively. The compound according to claim 1, wherein R ¹ and R ² are methyl, or a pharmaceutically acceptable salt, solvate, coordination complex or prodrug thereof. The compound according to claim 1, wherein the compound is a sodium salt of the following formula:

A pharmaceutical composition comprising a pharmaceutically acceptable carrier and the compound according to claim 1, or a pharmaceutically acceptable salt, solvate, coordination complex or prodrug thereof. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and the compound according to claim 2, or a pharmaceutically acceptable salt, solvate, coordination complex or prodrug thereof. A method for treating a respiratory disease mediated by a P2X3 receptor antagonist or a P2X2 / 3 receptor antagonist, wherein the compound according to claim 1 or a pharmaceutically acceptable substance thereof is acceptable to a subject in need of the treatment. A method comprising administering a therapeutically effective amount of a salt, a solvent, a coordination complex or a prodrug. The method according to claim 6, wherein the respiratory disease is a cough-related respiratory disease. The method of claim 7, wherein the cough-related respiratory disease is chronic obstructive pulmonary disease (COPD), bronchial spasm or asthma. The respiratory diseases are subacute cough, chronic cough, refractory cough, idiopathic chronic cough, cough associated with upper airway infection, cough after viral infection, idiopathic cough, idiopathic pulmonary fibrosis or smoking or The method of claim 6, wherein the cough is associated with a form of bronchitis. The method according to any one of claims 7 to 9, wherein R ¹ and R ² in the compound of formula (I) or a pharmaceutically acceptable salt, solvate, coordination complex or prodrug thereof are methyl. .. Treatment of the compound according to claim 1 or a pharmaceutically acceptable salt, solvate, coordination complex or prodrug thereof, which is a method for treating a bladder disorder and requires the treatment. Methods involving administration of an effective amount. 11. The method of claim 11, wherein the bladder disorder is bladder overactivity or urinary incontinence. Claimed that the bladder overactivity comprises one or more of urinary urgency, pollakiuria, changes in bladder capacity and micturition threshold, unstable bladder contraction, detrusor spasm, detrusor hyperreflexia and detrusor instability. 12. The method according to 12. 11. The method of claim 11, wherein the bladder disorder is interstitial cystitis. The method according to any one of claims 12 to 14, wherein R ¹ and R ² in the compound of formula (I) or a pharmaceutically acceptable salt, solvate, coordination complex or prodrug thereof are methyl. .. A therapeutically effective amount of the compound according to claim 1 or a pharmaceutically acceptable salt, solvate, coordination complex or prodrug thereof, which is a method for treating pain and requires the treatment. Methods involving the administration of. 16. The method of claim 16, wherein the pain is nociceptive pain. 16. The method of claim 16, wherein the pain is neuropathic pain. 16. The method of claim 16 or 17, wherein R ¹ and R ² in the compound of formula (I) or a pharmaceutically acceptable salt, solvate, coordination complex or prodrug thereof are methyl. The compound of the following formula (I):

(In the formula, R ¹ and R ² are selected from C ₁ to C ₆ alkyl, respectively)
It is a manufacturing method of
(A) The following compound 1 and

The compound of the following formula (IIa)

By reacting with, the compound of the following formula (III)

To form;
(B) A method comprising 5'-phosphorylation of a compound of formula (III) to obtain a compound of formula (I). 20. The method of claim 20, wherein R ¹ and R ² are methyl.