P2X

1. A method for treating a respiratory disorder in a patient, said method comprising administering to said patient a therapeutically effective amount of a compound of the structure of formula (I):

wherein:

R 1 is optionally substituted heteroaryl or NR 5 R 6 ;

R 2 is optionally substituted heteroaryl;

R 3 is H or C 1 to C 6 alkyl;

R 4 is optionally substituted heteroaryl;

R 5 and R 6 are, independently, selected from the group consisting of H, optionally substituted C 1 to C 6 alkyl, C 3 to C 6 cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, and CO(C 1 to C 6 alkyl); or

R 5 and R 6 are joined to form a 5 or 6-membered heterocyclic ring optionally substituted by one or more of halogen, C 1 to C 6 alkyl, C 1 to C 6 alkoxy, C 1 to C 6 hydroxyalkyl, C 3 to C 6 cycloalkyl, C 1 to C 6 alkyl containing 1 to 3 fluorine atoms, C 3 to C 6 cycloalkyl-C 1 to C 6 alkyl, or CONH 2 ;

or a pharmaceutically acceptable salt or prodrug thereof.

2. The method according to claim 1 , wherein the compound is of the structure of formula (II):

3. The method according to claim 1 , wherein the compound is of the structure of formula (III):

4. The method according to claim 1 , wherein the compound is of the structure of formula (IV):

5. The method according to claim 1 , wherein R 1 is:

optionally substituted heteroaryl;

heteroaryl substituted with one or more halogen, C 1 to C 6 alkyl, C 3 to C 6 cycloalkyl, C 3 to C 6 cycloalkyl-C 1 to C 6 alkyl, C 1 to C 6 hydroxyalkyl, C 1 to C 6 alkoxy, C 1 or C 6 alkyl containing 1 to 3 fluorine atoms, or CH 2 CONH 2 ;

oxadiazole, pyrazole, thiophene, or isoxazole;

oxadiazole substituted with one or more C 1 to C 6 alkyl, pyrazole substituted with one or more C 1 to C 6 alkyl, pyrazole substituted with one or more C 3 to C 6 cycloalkyl-C 1 to C 6 alkyl, pyrazole substituted with one or more C 1 to C 6 alkyl containing 1 to 3 fluorine atoms, pyrazole substituted with one or more CH 2 CONH 2 groups, thiophene substituted with one or more C 1 to C 6 alkyl, or isoxazole substituted with one or more C 1 to C 6 alkyl;

oxadiazole substituted with one C 1 to C 6 alkyl, pyrazole substituted with one C 1 to C 6 alkyl, pyrazole substituted with one C 3 to C 6 cycloalkyl-C 1 to C 6 alkyl, pyrazole substituted with one C 1 to C 6 alkyl containing 1 fluorine atom, pyrazole substituted with one CH 2 CONH 2 group, thiophene substituted with one C 1 to C 6 alkyl, or isoxazole substituted with one or two C 1 to C 6 alkyl;

oxadiazole substituted with one ethyl, pyrazole substituted with one CH 3 or CH 2 CH 3 , pyrazole substituted with one —CH 2 -cyclopropyl, pyrazole substituted with one CH 2 CH 2 F, pyrazole substituted with one CH 2 CONH 2 group, thiophene substituted with one CH 3 , or isoxazole substituted with two CH 3 ; or

2-ethyl-1,3,4-oxadiazole, 1-methyl-pyrazole, 1-ethyl-pyrazole, 1-cyclopropylmethane-pyrazole, 1-fluoroethane-pyrazole, 1-carboxamidomethyl-pyrazole, 2-methyl-thiophene, or 3,5-dimethyl-isoxazole.

6. The method according to claim 1 , wherein R 2 is:

heteroaryl substituted with one or more halogen, cyano, C 1 to C 6 alkyl, or C 1 to C 6 alkyl containing 1-3 fluorine atoms;

thiazole, thiophene, or furan;

thiazole substituted with C 1 to C 6 alkyl;

thiophene substituted with one or more of halogen, cyano, C 1 to C 6 alkyl, or C 1 to C 6 alkyl containing 1-3 fluorine atoms;

furan substituted with C 1 to C 6 alkyl; or

2-chloro-thiophene, 2-methyl-thiophene, 2-cyano-thiophene, 2-trifluoromethyl-thiophene, 5-methyl-thiazole, 2-methyl-thiazole, or 2-methyl-furan.

7. The method according to claim 1 , wherein R 4 is:

optionally substituted triazole, optionally substituted pyridine, optionally substituted pyridone, optionally substituted oxadiazole, optionally substituted pyrazine, or optionally substituted pyrimidine;

heteroaryl optionally substituted with C 1 to C 6 alkyl, C 3 to C 6 cycloalkyl, C 1 to C 6 alkoxy, or C 1 to C 6 trifluoroalkyl;

pyridine substituted with one or more C 1 to C 6 alkyl, C 3 to C 6 cycloalkyl, C 1 to C 6 alkoxy, or C 1 to C 6 trifluoroalkyl;

pyridine and the nitrogen atom of said pyridine is bound to an O-atom;

pyrazine substituted with one or more C 1 to C 6 alkyl;

pyrimidine substituted with one or more C 1 to C 6 alkyl or C 1 to C 6 alkoxy;

pyridone substituted with one or more C 1 to C 6 alkyl; or

1,2,4-triazole, 2-methyl-pyridine, 2-methoxy-pyridine, 1-oxo-pyridine, 1-oxo-2-methyl-pyridine, 1-oxo-2-trifluoromethyl-pyridine, 2-trifluoromethyl-pyridine, 2-cyclopropyl-pyridine, 1,3,4-oxadiazole, 1,2,4-oxadiazole, 3-methyl-1,2,4-oxadiazole, 2-methyl-1,3,4-oxadiazole, 2-methyl-pyrazine, 2-methyl-pyrimidine, 2-methoxy-pyrimidine, or 1-methyl-pyridone.

8. The method according to claim 1 , wherein one or both of R 5 and R 6 are:

optionally substituted phenyl;

phenyl substituted with fluorine or C 1 to C 6 alkoxy;

optionally substituted thiazole;

optionally substituted C 1 to C 6 alkyl or C 3 to C 6 cycloalkyl; or

4-fluoro-phenyl or 2-methoxy-phenyl.

9. The method according to claim 1 , wherein R 5 and R 6 are joined to form:

an optionally substituted heteroaryl or an optionally substituted 5 or 6-membered heterocyclic ring;

an optionally substituted pyrrolidine, piperazine or piperidine;

an optionally substituted imidazole, pyrazole, tetrazole, or triazole;

pyrrolidine optionally substituted with one or more C 1 to C 6 alkyl or C 1 to C 6 alkoxy;

imidazole substituted with one or more C 1 to C 6 alkyl;

a pyrazole substituted with one or more C 1 to C 6 alkyl;

tetrazole substituted with one or more C 3 to C 6 cycloalkyl, C 1 to C 6 alkyl, C 1 to C 6 hydroxyalkyl, C 1 to C 6 alkyl containing 1-3 fluorine atoms, and C 3 to C 6 cycloalkyl-C 1 to C 6 alkyl;

triazole substituted with one or more C 3 to C 6 cycloalkyl, C 1 to C 6 alkyl containing 1-3 fluorine atoms, and C 1 to C 6 alkyl;

a piperidine substituted with one or more C 1 to C 6 alkoxy, halogen, C 1 to C 6 alkyl containing 1-3 fluorine atoms, C 1 to C 6 alkyl, or CONH 2 ;

a piperazine substituted with one CONH 2 ; or

3-methoxy-pyrrolidine, 3-methyl-3-methoxy-pyrrolidine, 2,5-dimethyl-imidazole, 5-ethyl-pyrazole, 5-propyl-tetrazole, 5-cyclopropyl-tetrazole, 5-propyl-tetrazole, 5-isopropyl-tetrazole, 5-ethyl-tetrazole, 5-cyclobutyl-tetrazole, 5-cyclopropylmethyl-tetrazole, 5-methyl-tetrazole, 5-hydroxymethyl-tetrazole, 5-difluoromethyl-tetrazole, 5-(2,2,2-trifluoroethyl)-tetrazole, 5-(1,1-difluoroethyl)-tetrazole, 5-cyclopropyl-triazole, 5-difluoromethyl-triazole, 5-trifluoromethyl-triazole, 5-methyl-triazole, 5-isopropyl-triazole, 5-propyl-triazole, 5-ethyl-triazole, 5-tert-butyl-triazole, 5-cyclobutyl-triazole, 5-(1,1-difluoroethyl)-triazole, 5-(2,2,2-trifluoroethyl)-triazole, 3,5-dimethyl-1,2,4-triazole, 4-methyl-piperidine, 4,4-dimethyl-piperidine, 4,4-difluoro-piperidine, 4-methyl-4-carboxamido-piperidine, 4-fluoro-piperidine, 4-trifluoromethyl-piperidine, 4-fluoromethyl-piperidine, 4-methyl-4-methoxy-piperidine, 4-methoxy-piperidine, or 3-methoxy-piperidine, or 4-carboxamido-piperazine.

10. The method of claim 1 , comprising administering to the patient a pharmaceutical composition comprising an effective amount of the compound and optionally a pharmaceutically acceptable carrier.

11. The method according to claim 1 , wherein said administration is oral, intramuscular, rectal, cutaneous, subcutaneous, topical, transdermal, sublingual, nasal, vaginal, epidural, intrathecal, intravesical, or ocular.

12. A kit comprising one or more dosage forms for treating a respiratory disorder and instructions for administering the dosage forms to a patient, wherein the dosage forms comprise a compound of the structure of formula (I):

wherein:

R 1 is optionally substituted heteroaryl or NR 5 R 6 ;

R 2 is optionally substituted heteroaryl;

R 3 is H or C 1 to C 6 alkyl;

R 4 is optionally substituted heteroaryl;

R 5 and R 6 are, independently, selected from the group consisting of H, optionally substituted C 1 to C 6 alkyl, C 3 to C 6 cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, and CO(C 1 to C 6 alkyl); or

R 5 and R 6 are joined to form a 5 or 6-membered heterocyclic ring optionally substituted by one or more of halogen, C 1 to C 6 alkyl, C 1 to C 6 alkoxy, C 1 to C 6 hydroxyalkyl, C 3 to C 6 cycloalkyl, C 1 to C 6 alkyl containing 1 to 3 fluorine atoms, C 3 to C 6 cycloalkyl-C 1 to C 6 alkyl, or CONH 2 ;

or a pharmaceutically acceptable salt or prodrug thereof.

13. The kit according to claim 12 , wherein the compound is of the structure of formula (II):

14. The kit according to claim 12 , wherein the compound is of the structure of formula (III):

15. The kit according to claim 12 , wherein the compound is of the structure of formula (IV):

16. The method according to claim 1 , wherein the respiratory disorder is a cough.

17. The kit according to claim 12 , wherein the respiratory disorder is a cough.