Chemokine receptor binding compounds

1. A compound having the formula 1:

and pharmaceutically acceptable salts thereof,

wherein A is carbon or sulfur;

X is oxygen, sulfur, NR 2 , NOR 2 , NCN, NSO 2 R 2 , NAc, NNO 2 , CRNO 2 , NCOR 2 , C(CN) 2 or CRCN, provided X is oxygen if A is sulfur;

Y is a bond, O(CR 2 ) p , S(CR 2 ) p , NR(CR 2 ) p or (CR 2 ) p wherein one carbon in (CR 2 ) p may optionally be substituted and/or replaced with N, O or S;

n and p are independently 0 to 6;

m is 1 to 2, provided m is 1 if A is carbon;

E is H or methyl;

R 1 is an optionally substituted aryl or heteroaryl;

R 2 is H, an optionally substituted alkyl, a carbocyclic ring, a heterocyclic ring, an aryl, or a heteroaryl; and

R 3 is H; an optionally substituted alkyl, alkenyl or alkynyl; hydroxy, alkoxy, cyano, amino, amido, carboxyl, CO 2 R 2 , S═(O) p R 2 , CR═N—OR, O(CR 2 )CN, NR—COR 2 , SR 2 ; a carbocyclic ring, a heterocyclic ring, an aryl, or a heteroaryl;

R and R 4 are independently H, C 1-6 alkyl, or C 3-6 cycloalkyl;

wherein in each said optionally substituted alkyl, alkenyl or alkynyl, a carbon may be optionally substituted with halo, N, O, or S, and/or replaced with N, O or S; and

each carbocyclic ring, heterocyclic ring, aryl or heteroaryl may be optionally substituted and/or fused with a carbocyclic, aryl, heterocyclic, or heteroaryl ring.

2. The compound of claim 1 , wherein R 1 is phenyl, pyrimidinyl, pyridinyl, pyridine N-oxide, thienyl, isoxazolyl or pyrazolyl, each of which is optionally substituted by one or more halo, cyano, alkyl, alkoxy, amine, amide, cycloalkyl, heterocyclyl, aryl, heteroaryl, or N-oxide.

3. The compound of claim 1 , wherein R 2 is H, an optionally substituted alkyl, cycloalkyl, aryl or heteroaryl, each of which is optionally linked to one or more C 1-6 alkyl, alkoxy, trifluoromethyl, carboxylalkyl, cyano, halo, cycloalkyl, heterocyclyl, aryl, heteroaryl, or N-oxide.

4. The compound of claim 3 , wherein R 2 is phenyl, pyrimidinyl, pyridinyl, thiazolyl, furanyl, thienyl, or imidazolyl.

5. The compound of claim 1 , wherein R 3 is H, OH, cyano, NR 2 , SR, SOR, SO 2 R, CO 2 R, CONR 2 , or an optionally substituted alkyl or alkoxy, wherein R is independently H or C 1-6 alkyl; or R 3 may be a carbocyclic ring, a heterocyclic ring, an aryl, or a heteroaryl, each of which may be optionally substituted with halo, cyano, alkyl, alkoxy, cycloalkyl, heterocyclyl, aryl, heteroaryl, or N-oxide and/or fused with a carbocyclic, aryl, heterocyclic, or heteroaryl ring.

6. The compound of claim 5 , wherein R 3 is cyclohexyl, tetrahydropyran, morpholine, phenyl optionally fused with a 5-6 membered heterocyclic ring, pyridinyl, thienyl, C 1-6 straight or branched alkyl, bicyclo[4.2.0]octa-1,3,5-triene, indolyl, benzodioxolyl, dihydrobenzofuranyl, dihydroisobenzofuranyl, benzofuranyl, dihydrobenzodioxinyl, pyrrolidin-2-one, tetrazole, imidazole, dioxolane, or isoxazole.

7. The compound of claim 1 , where R 4 is hydrogen.

8. The compound of claim 1 , wherein n is 1.

9. The compound of claim 1 , wherein n=1 and R 2 is unsubstituted thiophenyl.

10. The compound of claim 1 , wherein R 1 is optionally substituted pyridyl.

11. The compound of claim 10 , wherein said optional substituents comprise halo.

12. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier.

13. The compound of claim 1 , wherein said compound is selected from the group consisting of:

and pharmaceutically acceptable salts thereof.

14. A pharmaceutical composition comprising a compound of claim 13 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.