Chemokine receptor binding heterocyclic compounds with enhanced efficacy

1. A compound of the formula

or a pharmaceutically acceptable salt thereof; and including any stereoisomeric forms thereof;

wherein n4 is 2-4;

each R 1 is independently H, halo, alkyl, alkoxy, or CF 3 ;

each R 2 is independently H or alkyl;

R 3 is H, alkyl, alkenyl, arylalkyl, or aryl;

each R 4 is independently H or alkyl, or the two R 4 groups may be taken together with the ring to which they are attached to form an optionally substituted 6-membered aromatic or heteroaromatic ring; and

each R 6 is independently H, arylalkyl, acyl, arylacyl, or arylsulfonyl, wherein the aryl moieties thereof optionally contain one or more heteroatoms selected from the group consisting of O, S, and N.

2. The compound of claim 1 wherein each R 1 is.

3. The compound of claim 1 wherein each R 2 is.

4. The compound of claim 1 wherein R 2 is H.

5. The compound of claim 1 wherein the two R 4 groups may be taken together with the ring to which they are attached to form an optionally substituted phenyl ring.

6. The compound of claim 1 wherein each R 6 is.

7. A pharmaceutical composition comprising a therapeutically effective amount of at least one compound of claim 1 , in admixture with a pharmaceutically acceptable excipient.

8. A compound selected from the group consisting of

N 1 -(1H-Benzimidazol-2-ylmethyl)-N 1 -(5,6,7,8-tetrahydro-quinolin-8-yl)-ethane-1,2-diamine;

N 1 -(1H-Benzimidazol-2-ylmethyl)-N 2 -(5-nitro-pyridin-2-yl)-N 1 -(5,6,7,8-tetrahydro-quinolin-8-yl)-ethane-1,2-diamine

N 1 -(6-2-[(1H-Benzimidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-ethylamino}-pyridin-3-yl)-acetamide;

N 1 -(1H-Benzimidazol-2-ylmethyl)-N 1 -(5,6,7,8-tetrahydro-quinolin-8-yl)-propane-1,3-diamine;

N 1 -(1H-Benzimidazol-2-ylmethyl)-N 2 -pyridin-2-ylmethyl-N 1 -(5,6,7,8-tetrahydro-quinolin-8-yl)-ethane-1,2-diamine;

N 1 -(1H-Benzimidazol-2-ylmethyl)-N 1 -(5,6,7,8-tetrahydro-quinolin-8-yl)-butane-1,4-diamine;

N′-(1H-benzimidazol-2-ylmethyl)-N′-(S)-5,6,7,8-tetrahydro-quinolin-8-yl-butane-1,4-diamine;

N 1 -(1-Methyl-1H-benzoimidazol-2-ylmethyl)-N 1 -(5,6,7,8-tetrahydro-quinolin-8-yl)-butane-1,4-diamine;

N 1 -[5-(4-Fluoro-phenyl)-1H-imidazol-2-ylmethyl]-N 1 -(5,6,7,8-tetrahydro-quinolin-8-yl)-butane-1,4-diamine;

N 1 -(1H-Benzimidazol-2-ylmethyl)-(5,6,7,8-tetrahydroquinolin-8-yl)-N-benzyl-1,4-butanediamine;

N 1 -(1H-Benzimidazol-2-ylmethyl)-N 4 -pyridin-2-ylmethyl-N 1 -(5,6,7,8-tetrahydro-quinolin-8-yl)-butane-1,4-diamine;

N 1 -(1H-Benzimidazol-2-ylmethyl)-N 4 -(1H-indol-3-ylmethyl)-N 1 -(5,6,7,8-tetrahydro-quinolin-8-yl)-butane-1,4-diamine;

1-N′-[4-(1H-Benzimidazol-2-ylmethyl)-(5,6,7,8-tetrahydroquinolin-8-yl)-amino]-aminobutane-N,N-dimethylformamidine;

N-{4-[(1H-benzoimidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-butyl}1-guanidine;

N′-(1H-benzimidazol-2-ylmethyl)-N′-(5,6,7,8-tetrahydro-quinolin-8-yl)-butane-1,4-diamine-N-(2-pyridinyl)-sulfonamide;

N-(1H-benzoimidazol-2-ylmethyl)-N′-pyrimidin-2-ylmethyl-N-(5,6,7,8-tetrahydro-quinolin-8-yl)-butane-1,4-diamine;

N-(1H-benzoimidazol-2-ylmethyl)-N′-(1H-imidazol-2-yl)-N-(5,6,7,8-tetrahydro-quinolin-8-yl)-butane-1,4-diamine;

N 1 -(1H-benzimidazol-2-ylmethyl)-N 4 -(1H-indol-2-ylmethyl)-N 1 -(5,6,7,8-tetrahydroquinolin-8-yl)-butane-1,4-diamine;

(1H-Benzimidazol-2-ylmethyl)-(5,6,7,8-tetrahydroquinolin-8-yl)-(N,N-dimethyl-4-amino-but-1-yl)-amine;

(1H-Benzimidazol-2-ylmethyl)-(5,6,7,8-tetrahydroquinolin-8-yl)-(N-allyl-4-amino-but-1-yl)-amine;

(1H-Benzimidazol-2-ylmethyl)-(5,6,7,8-tetrahydroquinolin-8-yl)-(N-methyl-4-amino-but-1-yl)-amine;

N′-(1H-imidazol-2-ylmethyl)-N′-(5,6,7,8-tetrahydro-quinolin-8-yl)-butane-1,4-diamine;

N-{4-[(1H-benzoimidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-butyl}-benzenesulfonamide;

(2S)-2-Amino-5-[(1H-benzimidazol-2-ylmethyl)-(5,6,7,8-tetrahydroquinolin-8-yl)-amino]-pentanoic acid;

N 1 -(1H-Benzimidazol-2-ylmethyl)-N 4 -cyclopropyl-N 1 -(5,6,7,8-tetrahydro-quinolin-8-yl)-butane-1,4-diamine;

N′-(1H-benzimidazol-2-ylmethyl)-3-methyl-3-phenyl-N′-(5,6,7,8-tetrahydro-quinolin-8-yl)-butane-1,4-diamine;

(1H-benzimidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-(1-phenyl-1-aminobut-4-yl)-amine;

(1H-benzimidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-(1-aminobutan-3-ol-4-yl)-amine;

(1H-benzimidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-(1-amino-3-fluoro-butan-4-yl)-amine;

(1H-Benzimidazol-2-ylmethyl)-(5,6,7,8-tetrahydroquinolin-8-yl)-(5-amino-pent-1-yl)-amine;

(1H-Benzimidazol-2-ylmethyl)-(5,6,7,8-tetrahydroquinolin-8-yl)-(6-amino-hex-1-yl)-amine;

N 1 -(1H-Benzimidazol-2-ylmethyl)-N 1 -(R)-5,6,7,8-tetrahydro-quinolin-8-yl-butane-1,4-diamine;

N 1 -(1H-Benzimidazol-2-ylmethyl)-2-methylene-N 1 -(5,6,7,8-tetrahydro-quinolin-8-yl)-butane-1,4-diamine;

N 1 -(1H-benzimidazol-2-ylmethyl)-3,3-difluoro-N 1 -(5,6,7,8-tetrahydroquinolin-8-yl)-butane-1,4-diamine;

N 1 -(1H-benzimidazol-2-ylmethyl)-2,2-difluoro-N 1 -(5,6,7,8-tetrahydroquinolin-8-yl)-butane-1,4-diamine;

(1H-benzimidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-(1-amino-2-(O-methyloxime)-butan-4-yl)-amine:

(1H-benzimidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-(1-amino-2-methylenyl-butan-4-yl)-amine;

(1H-benzimidazol-4-methoxy-2-ylmethyl)-(5,6,7,8-tetrahydroquinolin-8-yl)-(1-aminobutan-4-yl)-amine;

N 1 -(1H-Benzimidazol-2-ylmethyl)-N 1 -(4-methoxy-5,6,7,8-tetrahydro-quinolin-8-yl)-butane-1,4-diamine;

N 1 -(1H-benzimidazol-2-ylmethyl)-N 1- (3-methoxy-5,6,7,8-tetrahydroquinolin-8-yl)-butane-1,4-diamine;

N 1 -(1-Methyl-1H-benzoimidazol-2-ylmethyl)-N 1 -(S)-(5,6,7,8-tetrahydro-quinolin-8-yl)-butane-1,4-diamine;

N 1 -(1H-benzimidazol-2-ylmethyl)-N 1 -(2-chloro-5,6,7,8-tetrahydro-quinolin-8-yl)-butane-1,4-diamine;

N 1 -(1H-Benzoimidazol-2-ylmethyl)-N 1 -(2-methyl-5,6,7,8-tetrahydroquinolin-8-yl)-butane-1,4-diamine;

N 1 -(5,6-dimethyl-1H-benzimidazol-2-ylmethyl)-N 1 -(5,6,7,8-tetrahydro-quinolin-8-yl)-butane-1,4-diamine;

N 1 -[1-(1H-Benzimidazol-2-yl)-ethyl]-N 1 -(5,6,7,8-tetrahydro-quinolin-8-yl)-butane-1,4-diamine;

N 1 -(4-fluoro-1H-benzimidazol-2-ylmethyl)-N 1 -(5,6,7,8-tetrahydro-quinolin-8-yl)-butane-1,4-diamine;

N 1 -(4-Methoxy-1H-benzoindiazol-2-ylmethyl)-N 1 -(S)-(5,6,7,8-tetrahydro-quinolin-8-yl)-butane-1,4-diamine;

N 1 -(4-methyl-1H-benzoimidazol-2-ylmethyl)-N 1 -(5,6,7,8-tetrahydro-quinolin-8-yl)-butane-1,4-diamine;

N 1 -(4,5-dimethyl-1H-benzoimidazol-2-ylmethyl)-N 1 -(5,6,7,8-tetrahydro-quionlin-8-yl)-butane-1,4-diamine;

N 1 -(6-Fluoro-1H-benzimidazol-2-ylmethyl)-N 1 -(5,6,7,8-tetrahydroquinolin-8-yl)-butane-1,4-diamine;

N 1 -(1H-imidazo[4,5-b]pyridin-2-ylmethyl)-N 1 -(5,6,7,8-tetrahydro-quinolin-8-yl)-butane-1,4-diamine;

N 1 -(1H-imidazo[4,5-c]pyridin-2-ylmethyl)-N 1 -(5,6,7,8-tetrahydro-quinolin-8-yl)-butane-1,4-diamine;

N 1 -(5-trifluoromethyl-1H-benzoimidazol-2-ylmethyl)-N 1 -(5,6,7,8-tetrahydro-quinolin-8-yl)-butane-1,4-diamine;

N 1 -(1-allyl-1H-benzoimidazol-2-ylmethyl)-N 1 -(5,6,7,8-tetrahydro-quinolin-8-yl)-butane-1,4-diamine;

N 1 -(1-Allyl-1H-benzimidazol-2-ylmethyl)-N 1 -(S)-5,6,7,8-tetrahydro-quinolin-8-yl-butane-1,4-diamine;

N 1 -(1-cyclopropylmethyl-1H-benzoimidazol-2-ylmethyl)-N 1 -(5,6,7,8-tetrahydro-quinolin-8-yl)-butane-1,4-diamine;

N 1 -(1-pyridin-2-ylmethyl-1H-imidazol-2-ylmethyl)-N 1- (5,6,7,8-tetrahydro-quinolin-8-yl)-butane-1,4-diamine;

N 1 -(4-methyl-1H-imidazol-2-ylmethyl)-N 1 -(5,6,7,8-tetrahydro-quinolin-8-yl)-butane-1,4-diamine;

N 1 -(1-isopropyl-1H-imidazol-2-ylmethyl)-N 1 -(5,6,7,8-tetrahydro-quinolin-8-yl)-butane-1,4-diamine;

N 1 -[1-(2-methoxy-ethyl)-1H-imidazol-2-ylmethyl]-N 1 -(5,6,7,8-tetrahydro-quinolin-8-yl)-butane-1,4-diamine;

N 1 -(4-methyl-1-propyl-1H-imidazol-2-ylmethyl)-N 1 -(5,6,7,8-tetrahydro-quinolin-8-yl)-butane-1,4-diamine;

N 1 -(1-propyl-1H-imidazol-2-ylmethyl)-N 1 -(5,6,7,8-tetrahydroquinolin-8-yl)-butane-1,4-diamine;

N 1 -(1-methyl-1H-imidazol-2-ylmethyl)-N 1 -(5,6,7,8-tetrahydro-quinolin-8-yl)butane-1,4-diamine;

N 1 -(1-allyl-1H-imidazol-2-ylmethyl)-N 1 -(5,6,7,8-tetrahydroquinolin-8-yl)-butane-1,4-diamine;

N 1 -(4-Methoxymethyl-1H-imidazol-2-ylmethyl)-N 1 -(5,6,7,8-tetrahydro-quinolin-8-yl)-butane-1,4-diamine);

N 1 -(1-Allyl-1H-imidazol-2-ylmethyl)-N 1 -(S)-5,6,7,8-tetrahydro-quinolin-8-yl-butane-1,4-diamine;

N 1 -{2-[(1H-Benzimidazol-2-ylmethyl)-N 1 -(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-ethyl}-guanidine;

{4-[(1H-Benzimidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-butylamino}-acetic acid methyl ester;

pyrazine-2-carboxylic acid }4-[(1H-benzimidazol-2-ylmethyl)-(S)-5,6,7,8-tetrahydro-quinolin-8-yl-amino]-butyl}-amide;

Pyridine-2-carboxylic acid {3-[(1H-benzimidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-propyl}-amide;

Isoquinoline-3-carboxylic acid {3-[(1H-benzimidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-propyl}-amide;

N-{3-[(1H-benzoimidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-propyl}-6-hydroxy-nicotinamide;

N-3-[(1H-benzoimidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-propyl}-benzamide;

N-{3-[(1H-benzoimidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-propyl}-5-bromo-nicotinamide;

Cinnoline-4-carboxylic acid-13-[(1H-benzoimidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-propyl}-amide;

N-{4-[1H-benzolimidazol-2-ylmethyl)-(5,6,7,8-tetrahydroquinolin-8-yl)-amino]-butyl}-6-hydroxynicotinamide;

N-{4-[(1H-benzolimidazol-2-ylmethyl)-(5,6,7,8-tetrahydroquinolin-8-yl)-amino]-butyl}-benzamide;

pyridine-2-carboxylic acid {4-[1H-benzoimidazol-2-ylmethyl)-(5,6,7,8-tetrahydroquinolin-8-yl)-amino]-butyl}-amide;

N-{4-[(1H-Benzoimidazol-2-ylmethyl)-(5,6,7,8-tetrahydroquinolin-8-yl)-amino]-butyl}-5-bromo-nicotinamide;

quinoline-2-carboxylic acid {2-[(1H-benzoimidazol-2-ylmethyl)-(5,6,7,8-tetrahydroquinolin-8-yl)-amino]-butyl}-amide;

cinnoline-4-carboxylic acid {4-[(1H-benzoimidazol-2-ylmethyl)-5,6,7,8-tetrahydroquinolin-8-yl)-amino]-butyl}-amide;

N-{2-[(1H-benzoimidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-ethyl}-3,5-dicliloro-isonicotinamide;

N-{3-[(1H-benzoimidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-propyl}-3,5-dicliloro-isonicotinamide;

N-{4-[(1-allyl-1H-benzimidazol-2-ylmethyl)-(S)-5,6,7,8-tetrahydro-quinolin-8-ylamino]-butyl}-3,5-dicliloro-isonicotinamide;

N-{4-[(1H-benzimidazol-2-ylmethyl)-(R)-5,6,7,8-tetrahydro-quinolin-8-yl-amino]-butyl}-3,5-dicliloro-isonicotinamide;

N-{4-[(1-allyl-1H-imidazol-2-ylmethyl)-(S)-5,6,7,8-tetrahydro-quinolin-8-ylamino]-butyl}-3,5-dicliloro-isonicotinamide;

N-{4-[(1H-Benzimidazol-2-ylmethyl)-(S)-5,6,7,8-tetrahydro-quinolin-8-yl-amino]-butyl}-acetamide;

{4-[(1H-Benzimidazol-2-ylmethyl)-(S)-5,6,7,8-tetrahydro-quinolin-8-yl-amino]-butyl}-urea;

pyrazine-2-carboxylic acid {3-[(1H-benzimidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-propyl}-amide;

N-{3-[(1H-benzimidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-propyl}-guanidine;

{3-[(1H-benzimidazol-2-ylmethyl)-(5,6,7,8-tetrahydroquinolin-8-yl)-amino]-propyl}-urea; and

{2-[(1H-benzimidazol-2-ylmethyl)-(5,6,7,8-tetrahydroquinolin-8-yl)-amino]-ethyl}-urea;

or a pharmaceutically acceptable salt thereof.

9. A compound which is N 1 -(1H-Benzimidazol-2-ylmethyl)-N 1 -(5,6,7,8-tetrahydro-quinolin-8-yl)-butane-1,4-diamine or a pharmaceutically acceptable salt thereof.

10. The compound of claim 9 as a hydrobromide salt.