Chemokine receptor binding heterocyclic compounds

1. A compound of the Formula

or a pharmaceutically acceptable salt thereof,

wherein:

X is a monocyclic (5-6 membered) ring system containing at least one heteroatom selected from N, O and S, wherein said ring system may be optionally substituted with 1-2 substituents selected from the group consisting of halogen, C 1-4 alkyl, C 1-4 alkoxy, and optionally substituted phenyl, wherein said phenyl may be optionally substituted by halogen, C 1-4 alkyl, or C 1-4 alkoxy;

L 1 is CH 2 ;

Z is a tetrahydroquinoline or dihydroquinoline ring system;

Ar is an optionally substituted aromatic or heteroaromatic ring;

L 2 is CH 2 ;

L 3 is CO;

n is 0, 1 or 2;

each R 1 and R 2 is independently H or straight or branched chain or cyclic alkyl (1-6C) which may optionally be substituted, and wherein R 2 may be alkylene coupled to Y; and

Y is a pyridinyl ring, wherein the ring nitrogen may optionally be oxidized, and wherein said ring may be optionally substituted with 1-3 substituents selected from the group consisting of halogen, cyano, alkyl, —OR, —SR, —NR 2 , —NRCOR, —OOCR, —COR, -CONR2, —COOR, —NO 2 , and —CF 3 , where R is H or alkyl (1-6C).

2. The compound of claim 1 , wherein X is an optionally substituted imidazolyl, oxazolyl, thiazolyl, or pyrrolyl ring.

3. The compound of claim 1 which is a compound selected from the group consisting of

3,5-Dichloro-N-(4-{[(1H-imidazol-4-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzyl)-isonicotinamide;

3,5-Dichloro-N-(3-{[(1H-imidazol-4-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzyl)-isonicotinamide;

3,5-Dichloro-N-(4-{[(2-methyl-1H-imidazol-4-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzyl)-isonicotinamide;

3,5-Dichloro-N-(3-{[(2-methyl-1H-imidazol-4-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzyl)-isonicotinamide;

3,5-Dichloro-N-(4-{[(5-methyl-1H-imidazol-4-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzyl)-isonicotinamide;

3,5-Dichloro-N-(3-{[(5-methyl-1H-imidazol-4-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzyl)-isonicotinamide;

3,5-Dichloro-N-(4-{[(2,5-dimethyl-1H-imidazol-4-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzyl)-isonicotinamide;

3,5-Dichloro-N-(3-{[(2,5-dimethyl-1H-imidazol-4-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzyl)-isonicotinamide;

3,5-Dichloro-N-(4-{[(1-methyl-1H-imidazol-4-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzyl)-isonicotinamide;

3,5-Dichloro-N-(3-{[(1-methyl-1H-imidazol-4-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzyl)-isomcotmamide;

3,5-Dichloro-N-(4-[(1,2-dimethyl-1H-imidazol-4-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl -benzyl)-isonicotinamide;

3,5-Dichloro-N-(3-{[(1,2-dimethyl-1H-imidazol-4-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzyl)-isonicotinamide;

3,5-Dichloro-N-(4-{[(1,5-dimethyl-1H-imidazol-4-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzyl)-isonicotinamide;

3,5-Dichloro-N-(3-{[(1,5-dimethyl-1H-imidazol-4-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzyl)-isonicotinamide;

3,5-Dichloro-N-(4-{[(1H-imidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzyl)-isonicotinamide;

3,5-Dichloro-N-(3-{[(1H-imidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzyl)-isonicotinamide;

3,5-Dichloro-N-(4-{[(4-methyl-1H-imidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzyl)-isonicotinamide;

3,5-Dichloro-N-(3-{[(4-methyl-1H-imidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzyl)-isonicotinamide;

3,5-Dichloro-N-(4-{[[4-(2-fluoro-phenyl)-1H-imidazol-2-ylmethyl]-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzyl)-isonicotinamide;

3,5-Dichloro-N-(4-{[[4-(3-fluoro-phenyl)-1H-imidazol-2-ylmethyl]-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzyl)-isonicotinamide;

3,5-Dichloro-N-(4-{[[4-(4-fluoro-phenyl)-1H-imidazol-2-ylmethyl]-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzyl)-isonicotinamide;

3,5-Dichloro-N-(3-{[[4-(2-fluoro-phenyl)-1H-imidazol-2-ylmethyl]-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzyl)-isonicotinamide;

3,5-Dichloro-N-(3-{[[4-(3-fluoro-phenyl)-1H-imidazol-2-ylmethyl]-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzyl)-isonicotinamide;

3,5-Dichloro-N-(3-{[[4-(4-fluoro-phenyl)-1H-imidazol-2-ylmethyl]-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}benzyl)-isonicotinamide;

3,5-Dichloro-N-(4-{[(4-phenyl-1H-imidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}benzyl)-isonicotinamide;

3,5-Dichloro-N-(3-{[(4-phenyl-1H-imidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}benzyl)-isonicotinamide;

3,5-Dichloro-N-(4-{[(2-phenyl-3H-imidazol-4-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}benzyl)-isonicotinamide;

3,5-Dichloro-N-(4-{[[2-(2-methoxy-phenyl)-3H-imidazol-4-ylmethyl]-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}benzyl)-isonicotinamide;

3,5-Dichloro-N-(4-{[[2-(3-methoxy-phenyl)-3H-imidazol-4-ylmethyl]-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}benzyl)-isonicotinamide;

3,5-Dichloro-N-(4-{[[2-(4-methoxy-phenyl)-3H-imidazol-4-ylmethyl]-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}benzyl)-isonicotinamide;

3,5-Dichloro-N-(3-{[[2-(2-methoxy-phenyl)-3H-imidazol-4-ylmethyl]-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}benzyl)-isonicotinamide;

3,5-Dichloro-N-(3-{[[2-(3-methoxy-phenyl)-3H-imidazol-4-ylmethyl]-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}benzyl)-isonicotinamide;

3,5-Dichloro-N-(3-{[[2-(4-methoxy-phenyl)-3H-imidazol-4-ylmethyl]-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}benzyl)-isonicotinamide;

3,5-Dichloro-N-(4-{[[4-(2-methoxy-phenyl)-1H-imidazol-2-ylmethyl]-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}benzyl)-isonicotinamide;

3,5-Dichloro-N-(4-{[[4-(3-methoxy-phenyl)-1H-imidazol-2-ylmethyl]-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}benzyl)-isonicotinamide;

3,5-Dichloro-N-(4-{[[4-(4-methoxy-phenyl)-1H-imidazol-2-ylmethyl]-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}benzyl)-isonicotinamide;

3,5-Dichloro-N-(3-{[[4-(2-methoxy-phenyl)-1H-imidazol-2-ylmethyl]-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}benzyl)-isonicotinamide;

3,5-Dichloro-N-(3-{[[4-(3-methoxy-phenyl)-1H-imidazol-2-ylmethyl]-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}benzyl)-isonicotinamide;

3,5-Dichloro-N-(3-{[[4-(4-methoxy-phenyl)-1H-imidazol-2-ylmethyl]-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}benzyl)-isonicotinamide;

3,5-Dichloro-N-(4-{[(3H-pyrrol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzyl)-isonicotinamide;

3,5-Dichloro-N-(3-{[(3H-pyrrol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzyl)-isonicotinamide;

3,5-Dichloro-N-(4-{[(5-methyl-3H-pyrrol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzyl)-isonicotinamide;

3,5-Dichloro-N-(4-{[(4-methyl-3H-pyrrol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzyl)-isonicotinamide;

3,5-Dichloro-N-(3-{[(5-methyl-3H-pyrrol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzyl)-isonicotinamide;

3,5-Dichloro-N-(3-{[(4-methyl-3H-pyrrol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzyl)-isonicotinamide;

3,5-Dichloro-N-(4-{[oxazol-2-ylmethyl-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzyl)-isonicotinamide;

3,5-Dichloro-N-(4-{[(4-methyl-oxazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzyl)-isonicotinamide;

3,5-Dichloro-N-(4-{[(5-methyl-oxazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzyl)-isonicotinamide;

3,5-Dichloro-N-(4-{[oxazol-4-ylmethyl-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzyl)-isonicotinamide;

3,5-Dichloro-N-(4-{[(2-methyl-oxazol-4-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzyl)-isonicotinamide;

3,5-Dichloro-N-(3-{[oxazol-2-ylmethyl-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzyl)-isonicotinamide;

3,5-Dichloro-N-(3-{[(4-methyl-oxazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzyl)-isonicotinamide;

3,5-Dichloro-N-(3-{[(5-methyl-oxazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzyl)-isonicotinamide;

3,5-Dichloro-N-(3-{[oxazol-4-ylmethyl-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzyl)-isonicotinamide;

3,5-Dichloro-N-(3-{[(2-methyl-oxazol-4-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzyl)-isonicotinamide;

3,5-Dichloro-N-(4-{[(5,6,7,8-tetrahydro-quinolin-8-yl)-thiazol-2-ylmethyl-amino]-methyl}-benzyl)-isonicotinamide;

3,5-Dichloro-N-(4-{[(4-methyl-thiazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzyl)-isonicotinamide;

3,5-Dichloro-N-(4-{[(5-methyl-thiazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzyl)-isonicotinamide;

3,5-Dichloro-N-(4-{[(5,6,7,8-tetrahydro-quinolin-8-yl)-thiazol-4-ylmethyl-amino]-methyl}benzyl)-isonicotinamide;

3,5-Dichloro-N-(4-{[(2-methyl-thiazol-4-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}benzyl)-isonicotinamide;

3,5-Dichloro-N-(3-{[(5,6,7,8-tetrahydro-quinolin-8-yl)-thiazol-2-ylmethyl-amino]-methyl}-benzyl)-isonicotinamide;

3,5-Dichloro-N-(3-{[(4-methyl-thiazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}benzyl)-isonicotinamide;

3,5-Dichloro-N-(3-{[(5-methyl-thiazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}benzyl)-isonicotinamide;

3,5-Dichloro-N-(3-{[(5,6,7,8-tetrahydro-quinolin-8-yl)-thiazol-4-ylmethyl-amino]-methyl}-benzyl)-isonicotinamide;

3,5-Dichloro-N-(3-{[(2-methyl-thiazol-4-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}benzyl)-isonicotinamide;

N-(4-{[(3H-Imidazol-4-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzyl)-2,4-dimethyl-nicotinamide;

N-(3-{[(3H-Imidazol-4-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzyl)-2,4-dimethyl-nicotinamide;

2,4-Dimethyl-N-(4-{[(3-methyl-3H-imidazol-4-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzyl)-nicotinamide;

2,4-Dimethyl-N-(3-{[(3-methyl-3H-imidazol-4-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzyl)-nicotinamide;

2,4,N-Trimethyl-N-(4-{[(3-methyl-3H-imidazol-4-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzyl)-nicotinamide;

2,4,N-Trimethyl-N-(3-{[(3-methyl-3H-imidazol-4-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzyl)-nicotinamide;

N-(4-{[(1H-Imidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzyl)-2,4-dimethyl-nicotinamide;

N-(3-{[(1H-Imidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzyl)-2,4-dimethyl-nicotinamide;

2,4-Dimethyl-N-(4-{[(1-methyl-1H-imidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzyl)-nicotinamide;

2,4-Dimethyl-N-(3-{[(1-methyl-1H-imidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzyl)-nicotinamide;

2,4-Dimethyl-N-(4-{[oxazol-2-ylmethyl-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzyl)-nicotinamide;

2,4-Dimethyl-N-(3-{[oxazol-2-ylmethyl-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzyl)-nicotinamide;

2,4-Dimethyl-N-(4-{[oxazol-5-ylmethyl-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzyl)-nicotinamide;

2,4-Dimethyl-N-(3-{[oxazol-5-ylmethyl-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzyl)-nicotinamide;

2,4-Dimethyl-N-(4-{[(5,6,7,8-tetrahydro-quinolin-8-yl)-thiazol-5-ylmethyl-amino]-methyl}-benzyl)-nicotinamide;

2,4-Dimethyl-N-(3-{[(5,6,7,8-tetrahydro-quinolin-8-yl)-thiazol-5-ylmethyl-amino]-methyl}-benzyl)-nicotinamide;

2,4-Dimethyl-N-(4-{[(5,6,7,8-tetrahydro-quinolin-8-yl)-thiazol-2-ylmethyl-amino]-methyl}-benzyl)-nicotinamide; and

2,4-Dimethyl-N-(3-{[(5,6,7,8-tetrahydro-quinolin-8-yl)-thiazol-2-ylmethyl-amino]-methyl}-benzyl)-nicotinamide.

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

5. A compound of claim the formula

wherein l s 0-3, and R′ is OH, MeO, SH, SMe, CN, CO 2 Me, F, Cl, Br, NO 2 , CH 3 CO, NH 2 , NHCH 3 , N(CH 3 ) 2 , CH 3 CONH, CH 3 SO 2 NH, CONH 2 , SO 2 NH 2 , CF 3 , or Me; k is 0-2;

each of Z 1 and Z 2 is independently CH or CR′;

Z 3 is N;

X is a tetrahydroquinoline or dihydroquinoline ring system;

L 2 is CH 2 ; and

L 3 is CO.

6. A pharmaceutical composition comprising the compound of claim 5 and a pharmaceutically acceptable carrier.