DIAMINOPYRIMIDINE P2X3 AND P2X2/3 RECEPTOR MODULATORS FOR USE IN THE TREATMENT OF COUGH
Methods for treating cough, chronic cough and urges to cough associated with respiratory diseases with a P2X3 and/or a P2X2/3 receptor antagonist, the methods comprising administering to a subject in need thereof an effective amount of a compound of Formula (I): or a pharmaceutically acceptable salt thereof, wherein R 1 and R 2 are as defined herein.
1 . A method for treating chronic cough, comprising administering to a patient with chronic cough about 15 mg twice daily of a compound of Formula (I):
or a pharmaceutically acceptable salt thereof, wherein:
R 1 is hydrogen or C 1 -C 6 alkyl; and
R 2 is: alkyl; aminosulfonyl; halo; amido; haloalkyl; alkoxy; hydroxy; haloalkoxy; nitro; hydroxyalkyl; alkoxyalkyl; hydroxyalkoxy; alkynylalkoxy; alkylsulfonyl; arylsulfonyl; carboxyalkyl; cyano or alkylcarbonyl; and
wherein the method exhibits a reduced taste disturbance relative to a taste disturbance resulting from administering a dose of about 100 mg or greater of the compound of formula (I) or the pharmaceutically acceptable salt thereof twice daily to a patient with chronic cough.
2 . The method of claim 1 , wherein the chronic cough is idiopathic or treatment resistant cough.
3 - 4 . (canceled)
5 . The method of claim 1 , wherein the compound of Formula (I), or the pharmaceutically acceptable salt thereof, is administered twice daily for days, weeks, months or years.
6 . The method of claim 1 , wherein the chronic cough is refractory chronic cough.
7 . The method of claim 1 , wherein the reduced taste disturbance is relative to a taste disturbance resulting from administering about 100 mg of the compound of Formula (I) or the pharmaceutically acceptable salt thereof twice daily to a patient with chronic cough.
8 . The method of claim 1 , wherein the chronic cough is daytime cough.
9 - 10 . (canceled)
11 . The method of claim 1 , wherein the compound is selected from:
or a pharmaceutically acceptable salt thereof.
12 . The method of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
13 - 20 . (canceled)
21 . A method for treating chronic cough, comprising administering to a patient with chronic cough about 15 mg twice daily of a pharmaceutically acceptable salt of the following compound:
wherein the method exhibits a reduced taste disturbance relative to a taste disturbance resulting from administering a dose of about 100 mg or greater of the pharmaceutically acceptable salt of the compound of formula (I) twice daily to a patient with chronic cough.
22 . The method of claim 21 , wherein the reduced taste disturbance is relative to a taste disturbance resulting from administering about 100 mg of the pharmaceutically acceptable salt of the compound of formula (I) twice daily to a patient with chronic cough.
23 - 26 . (canceled)
27 . The method of claim 21 , wherein the reduced taste disturbance is relative to a taste disturbance resulting from administering about 600 mg of the pharmaceutically acceptable salt of the compound of formula (I) twice daily to a patient with chronic cough.