Diaminopyrimidines as P2X

1. A compound of formula I:

or a pharmaceutically acceptable salt thereof,

wherein:

X is:

—O—;

D is an optional oxygen;

A is N and E, G, J, Y and Z are CR a ;

R 1 is:

alkyl;

alkenyl;

alkynyl;

cycloalkyl;

cycloalkenyl;

halo;

haloalkyl; or

hydroxyalkyl;

each R a is independently:

hydrogen;

alkyl;

alkenyl;

amino;

aminosulfonyl;

halo;

amido;

haloalkyl;

alkoxy;

hydroxy;

haloalkoxy;

nitro;

hydroxyalkyl;

alkoxyalkyl;

hydroxyalkoxy;

alkynylalkoxy;

alkylsulfonyl;

arylsulfonyl;

cyano;

aryl;

heteroaryl;

heterocyclyl;

heterocyclylalkoxy;

aryloxy;

heteroaryloxy;

aralkyloxy;

heteroaralkyloxy;

optionally substituted phenoxy;

—C≡C—R b —;

—(CH 2 ) m —(Z) n —(CO)—R c ;

—(CH 2 ) m —(Z) n —SO 2 —(NR d ) n —R c ;

wherein

m and n each independently is 0 or 1,

Z is O or NR d ,

R b is hydrogen; alkyl; aryl; aralkyl; heteroaryl; heteroaralkyl; hydroxyalkyl; alkoxyalkyl; alkylsulfonylalkyl; aminoalkyl; cyanoalkyl; alkylsilyl, cycloalkyl, cycloalkylalkyl; heterocyclyl; and heterocyclylalkyl;

R c is hydrogen, alkyl, hydroxy, alkoxy, amino, hydroxyalkyl or alkoxyalkyl, and

each R d is independently hydrogen or alkyl;

R 6 is:

hydrogen;

alkyl;

halo;

haloalkyl;

amino; or

alkoxy;

R 7 and R 8 each independently is:

hydrogen;

alkyl;

cycloalkyl;

cycloalkylalkyl;

haloalkyl;

haloalkoxy;

hydroxyalkyl;

alkoxyalkyl;

alkylsulfonyl;

alkylsulfonylalkyl;

aminocarbonyloxyalkyl;

hydroxycarbonylalkyl;

hydroxyalkyloxycarbonylalkyl;

aryl;

aralkyl;

arylsulfonyl;

heteroaryl;

heteroarylalkyl;

heteroarylsulfonyl;

heterocyclyl;

heterocyclylalkyl; or

—(C═O)—R e ;

wherein

R e is alkyl, alkoxy, cycloalkyl, cycloalkoxy, cycloalkylalkyl, cycloalkylalkoxy, aryl, aryloxy, heteroaryl, heteroaryloxy, aralkyl, aralkoxy, heteroaralkyl, heteroaralkoxy, —(CH 2 ) p —C(═O)—R f , —(CH═CH)—C(═O)—R f , or —CH(NH 2 )—R g

wherein

R f is hydrogen, hydroxy, alkyl, alkoxy, cycloalkyl, cycloalkoxy, cycloalkylalkyl, cycloalkylalkoxy, aryl, aryloxy, heteroaryl, heteroaryloxy, aralkyl, aralkoxy, heteroaralkyl, heteroaralkoxy, or amino;

p is 2 or 3;

R g is hydrogen, alkyl, hydroxyalkyl, aminoalkyl, optionally substituted phenyl, benzyl, guanidinylalkyl, carboxyalkyl, amidoalkyl, thioalkyl or imidazolalkyl.

2. The compound of claim 1 , wherein R 1 is ethyl, isopropyl, iodo, ethynyl or cyclopropyl.

3. The compound of claim 2 , wherein each R a is independently hydrogen, halo, alkyl, alkoxy, hydroxy, haloalkoxy, alkylsulfonyl or —C≡C—R b —.

4. The compound of claim 3 , wherein R 7 and R 8 are hydrogen.

5. The compound of claim 3 , wherein one of R 7 and R 8 is hydrogen and the other is alkyl, hydroxyalkyl or haloalkyl.

6. The compound of claim 4 , wherein R a is hydrogen, alkyl, alkoxy, hydroxy, halo, haloalkyl or haloalkoxy.

7. The compound of claim 5 , wherein R a is hydrogen, alkyl or alkoxy.

8. A pharmaceutical composition comprising:

(a) a pharmaceutically acceptable excipient; and

(b) a compound of claim 1 .

9. A method for treating, said method comprising administering to a subject in need thereof an effective amount of a compound of claim 1 .

10. A method for treating asthma, said method comprising administering to a subject in need thereof an effective amount of a compound of claim 1 .