CXCR4 receptor antagonists

1. A compound of formula (I) or a pharmaceutically acceptable salt thereof:

wherein:

R 1 is selected from C 1-4 -alkyl, cyano, —COR 3 , —CONR 3 R 4 , and heteroaryl, wherein

(a) said heteroaryl is optionally substituted with one more substituents independently selected from halogen, hydroxy, cyano, nitro, C 1-6 -alkyl, C 3-5 -cycloalkyl, C 1-4 -alkoxy, fluoro-C 1-6 -alkyl, fluoro-C 1-4 -alkoxy, C 1-4 -alkoxy-C 1-4 -alkyl, fluoro-C 1-4 -alkoxy-C 1-4 -alkyl, C 6-10 -aryl, heteroaryl, —NR 5A R 5B , —C 1-4 -alkyl-NR 5A R 5B , —NR 4 C(O)O—C 1-4 -alkyl, —NR 4 C(O)—C 1-4 -alkyl, —NR 4 C(O)O-fluoro-C 1-4 -alkyl, —NR 4 C(O)-fluoro-C 1-4 -alkyl, —NR 4 C(O)NR 5A R 5B , —C(O)NR 5A R 5B , —C(O)R 4 , —C(O)OR 4 , —NR 4 S(O) 2 —C 1-4 -alkyl, and —NR 4 S(O) 2 -fluoro-C 1-4 -alkyl, and

(b) said C 1-4 -alkyl is optionally substituted with one or more substituents independently selected from fluorine, hydroxyl, and C 1-4 -alkoxy;

U 1 , U 2 and U 3 are each independently —C(H)═ or —N═ so as to form a 6-membered heteroaryl ring, the heteroaryl ring having a configuration selected from (a), (b), (c), (d), and (f), wherein (a) is U 1 is —N═ and U 2 and U 3 are each —C(H)═; (b) is U 1 and U 2 are each —N═ and U 3 is —C(H)═; (c) is U 2 is —N═ and U 1 and U 3 are each —C(H)═; (d) U 3 is —N═ and U 1 and U 2 are each —C(H)═; and (f) is U 1 and U 3 are each —N═ and U 2 is —C(H)═;

wherein the heteroaryl ring is optionally substituted with one more substituents independently selected from halogen, cyano, nitro, C 1-4 -alkyl, C 1-4 -alkoxy, fluoro-C 1-4 -alkyl, and fluoro-C 1-4 -alkoxy, and wherein

n is 1, so as to form a piperazine ring, or n is 2, so as to form a homopiperazine ring, wherein either ring is optionally substituted with one more substituents independently selected from fluorine, hydroxyl, C 1-4 -alkyl, a divalent C 1-4 -alkylene radical which forms a bridge between ring carbons of said homopiperazine or piperazine, C 1-4 -alkoxy, fluoro-C 1-4 -alkyl, a divalent fluoro-C 1-4 -alkylene radical which forms a bridge between ring carbons of said homopiperazine or piperazine and fluoro-C 1-4 -alkoxy;

R 2 is selected from radicals of formulae (N)-(R) inclusive, any of which is optionally substituted with one more substituents independently selected from fluorine, hydroxyl, C 1-4 -alkyl, C 1-4 -alkoxy, fluoro-C 1-4 -alkyl, and fluoro-C 1-4 -alkoxy, wherein the bond marked * is attached to the piperazine or homopiperazine ring:

and o and p are each independently 1 or 2, and W is O or NR 9 ;

R 3 is selected from hydrogen, C 1-6 -alkyl, C 3-5 -cycloalkyl, C 3-5 -cycloalkyl-C 1-4 -alkyl, heterocyclyl, heterocyclyl-C 1-4 -alkyl, C 6-10 -aryl, heteroaryl, C 6-10 -aryl-C 1-4 -alkyl, and heteroaryl-C 1-4 -alkyl, wherein

(i) said C 1-6 -alkyl, C 3-5 -cycloalkyl, heterocyclyl or the heterocyclyl part of said heterocyclyl-C 1-4 -alkyl, or the C 1-6 -alkyl part of said heterocyclyl-C 1-4 -alkyl, C 6-10 -aryl-C 1-4 -alkyl or heteroaryl-C 1-4 -alkyl, is optionally substituted with one or more substituents independently selected from fluorine, hydroxy, cyano, C 1-4 -alkoxy, and —NR 5A R 5B , and

(ii) said C 6-10 -aryl or heteroaryl, or the C 6-10 -aryl part of said C 6-10 -aryl-C 1-4 -alkyl or the heteroaryl part of said heteroaryl-C 1-4 -alkyl, is optionally substituted with one more substituents independently selected from halogen, hydroxy, cyano, nitro, C 1-4 -alkyl, C 1-4 -alkoxy, fluoro-C 1-4 -alkyl, fluoro-C 1-4 -alkoxy, C 1-4 -alkoxy-C 1-4 -alkyl, fluoro-C 14 -alkoxy-C 1-4 -alkyl, —NR 5A R 5B , —C 1-4 -alkyl-NR 5A R 5B , —NR 4 C(O)O—C 1-4 alkyl, —NR 4 C(O)—C 1-4 alkyl, —NR 4 C(O)O-fluoro-C 1-4 alkyl, —NR 4 C(O)-fluoro-C 1-4 alkyl, —NR 4 C(O)NR 5A R 5B , —C(O)NR 5A R 5B , —C(O)R 4 , —C(O)OR 4 , —NR 4 S(O) 2 —C 1-4 alkyl, and —NR 4 S(O) 2 -fluoro-C 1-4 alkyl;

R 4 , R 5A and R 5B are each independently selected from hydrogen, C 1-4 -alkyl, and fluoro-C 1-4 -alkyl,

or

R 5A and R 5B together with the nitrogen atom to which they are bound, form a 4- to 7-membered saturated heterocyclic ring or a heteroaryl ring, said ring being optionally substituted with one or more substituents independently selected from fluorine, hydroxyl, C 1-4 -alkyl, fluoro-C 1-4 -alkyl, and C 1-4 -alkoxy,

or

R 3 and R 4 , together with the nitrogen atom to which they are bound, form a 4- to 7-membered saturated heterocyclic ring or a heteroaryl ring, said ring being optionally substituted with one or more substituents independently selected from fluorine, hydroxyl, C 1-4 -alkyl, fluoro-C 1-4 -alkyl, and C 1-4 -alkoxy; and

R 6 is selected from C 1-6 -alkyl, C 3-5 -cycloalkyl, C 3-5 -cycloalkyl-C 1-4 -alkyl, heterocyclyl, heterocyclyl-C 1-4 -alkyl, C 6-10 -aryl-C 1-4 -alkyl, and C 6-10 -aryl, wherein

(iii) said C 1-6 -alkyl, C 3-5 -cycloalkyl, heterocyclyl, or the C 1-6 -alkyl part of said heterocyclyl-C 1-4 -alkyl or C 6-10 -aryl-C 1-4 -alkyl, or the heterocyclyl part of said heterocyclyl-C 1-4 -alkyl is optionally substituted with one or more substituents independently selected from fluorine, hydroxyl, and C 1-4 -alkoxy, and

(iv) said C 6-10 -aryl or the C 6-10 -aryl part of said C 6-10 -aryl-C 1-4 -alkyl is optionally substituted with one more substituents independently selected from halogen, hydroxy, cyano, nitro, C 1-4 -alkyl, C 1-4 -alkoxy, fluoro-C 1-4 -alkyl, fluoro-C 1-4 -alkoxy, C 1-4 -alkoxy-C 1-4 -alkyl, and fluoro-C 1-4 -alkoxy-C 1-4 -alkyl;

R 7 is selected from C 1-6 -alkyl, C 3-5 -cycloalkyl, C 3-5 -cycloalkyl-C 1-4 -alkyl, heterocyclyl, heterocyclyl-C 1-4 -alkyl, C 6-10 -aryl-C 1-4 -alkyl, C 6-10 -aryl, and —NR 10A R 10B , wherein

(v) said C 1-6 -alkyl, C 3-5 -cycloalkyl, heterocyclyl, or the C 1-6 -alkyl part of said heterocyclyl-C 1-4 -alkyl or C 6-10 -aryl-C 1-4 -alkyl, or the heterocyclyl part of said heterocyclyl-C 1-4 -alkyl is optionally substituted with one or more substituents independently selected from fluorine, hydroxyl, and C 1-4 -alkoxy, and

(vi) said C 6-10 -aryl or the C 6-10 -aryl part of said C 6-10 -aryl-C 1-4 -alkyl is optionally substituted with one more substituents independently selected from halogen, hydroxy, cyano, nitro, C 1-4 -alkyl, C 1-4 -alkoxy, fluoro-C 1-4 -alkyl, fluoro-C 1-4 -alkoxy, C 1-4 -alkoxy-C 1-4 -alkyl, and fluoro-C 1-4 -alkoxy-C 1-4 -alkyl;

R 9 is selected from hydrogen, C 3-5 -cycloalkyl, C 1-6 -alkyl, and C 6-10 -aryl-C 1-4 -alkyl wherein any alkyl residue or cycloalkyl or C 6-10 -aryl ring system is optionally substituted with one or more substituents independently selected from halogen, hydroxyl, and C 1-4 -alkoxy;

and

R 10A and R 10B are each independently selected from hydrogen and C 1-6 -alkyl, wherein said C 1-6 -alkyl is optionally substituted with one or more substituents independently selected from fluorine, hydroxyl, and C 1-4 -alkoxy,

or

R 10A and R 10B , together with the nitrogen atom to which they are bound, form a 4- to 7-membered saturated heterocyclic ring or a heteroaryl ring, optionally substituted with one or more substituents independently selected from fluorine, hydroxyl, C 1-4 -alkyl, fluoro-C 1-4 -alkyl, and C 1-4 -alkoxy; provided that

when n=1, then R 2 is not piperidine wherein p=1, and o=2.

2. A compound as claimed in claim 1 wherein R 1 is CONR 3 R 4 or heteroaryl wherein said heteroaryl is optionally substituted with one more substituents independently selected from halogen, cyano, C 1-6 -alkyl, C 3-5 -cycloalkyl, C 1-4 -alkoxy, fluoro-C 1-6 -alkyl, fluoro-C 1-4 -alkoxy, and heteroaryl.

3. A compound as claimed in claim 1 wherein R 1 is heteroaryl selected from benzoxazolyl, indolyl, azaindolyl, imidazolyl, benzimidazolyl, oxazolyl, oxadiazolyl, and tetrazolyl, any of which being optionally substituted with one more substituents independently selected from halogen, hydroxy, cyano, nitro, C 1-6 -alkyl, C 3-5 -cycloalkyl, C 1-4 -alkoxy, fluoro-C 1-6 -alkyl, fluoro-C 1-4 -alkoxy, C 1-4 -alkoxy-C 1-4 -alkyl, fluoro-C 1-4 -alkoxy-C 1-4 -alkyl, C 6-10 -aryl, heteroaryl, —NR 5A R 5B , —C 1-4 -alkyl-NR 5A R 5B , —NR 4 C(O)O—C 1-4 -alkyl, —NR 4 C(O)—C 1-4 -alkyl, —NR 4 C(O)O-fluoro-C 1-4 -alkyl, —NR 4 C(O)-fluoro-C 1-4 -alkyl, —NR 4 C(O)NR 5A R 5B , —C(O)NR 5A R 5B , —C(O)R 4 , —C(O)OR 4 , —NR 4 S(O) 2 —C 1-4 -alkyl, and —NR 4 S(O) 2 -fluoro-C 1-4 -alkyl.

4. A compound as claimed in claim 1 wherein R 1 is CONR 3 R 4 wherein R 4 is hydrogen or methyl.

5. A compound as claimed in claim 4 wherein R 3 is selected from tetrahydropyranyl, isopropylmethyl, tetrahydropyranylmethyl, imidazolylethyl, methoxyethyl, N-methylimidazolylmethyl, tetrahydrofuranylmethyl, 1-fluoroethyl, oxazolylmethyl, pyridylmethyl, 2,2-difluoromethyl, tetrahydrofuranyl, methyl, ethyl, n- or iso-propyl, n-sec- or tert-butyl, cyclopropyl, hydroxyethyl, cyanoethyl, phenyl, chlorophenyl, methoxyphenyl, methylphenyl, hydroxyphenyl, thiazoloylmethyl, indolyl, methoxypropyl, tetrahydroisoquinolinyl, furylmethyl, pyridylethyl, thiazolyl, and cyclopropylmethyl.

6. A compound according to claim 4 wherein R 3 is pyridyl optionally substituted with one or more substituents selected from halogen, C 1-4 -alkyl, C 1-4 -alkoxy, and fluoro-C 1-4 -alkyl.

7. A compound according to claim 4 where R 3 is 4-pyridyl optionally substituted with one or more methyl group.

8. A compound as claimed in claim 1 , wherein n is 2 so as to form a homopiperazine ring, the homopiperazine ring being optionally substituted with one more substituents independently selected from fluorine, hydroxyl, C 1-4 -alkyl, a divalent C 1-4 -alkylene radical which forms a bridge between ring carbons of said homopiperazine, C 1-4 -alkoxy, fluoro-C 1-4 -alkyl or a divalent fluoro-C 1-4 -alkylene radical which forms a bridge between ring carbons of said homopiperazine and fluoro-C 1-4 -alkoxy.

9. A compound as claimed in claim 1 , wherein n is 1 so as to form a piperazine ring, the piperazine ring being optionally substituted with one more substituents independently selected from fluorine, hydroxyl, C 1-4 -alkyl, a divalent C 1-4 -alkylene radical which forms a bridge between ring carbons of said piperazine, C 1-4 -alkoxy, fluoro-C 1-4 -alkyl or a divalent fluoro-C 1-4 -alkylene radical which forms a bridge between ring carbons of said piperazine, and fluoro-C 1-4 -alkoxy.

10. A compound as claimed in claim 8 wherein R 2 is a 4-piperidine radical of formula (N) wherein o is 2 and p is 1, a 4-azepine radical of formula (N) wherein o is 2 and p is 2, a 1,4-cyclohexyl radical of formula (R) or a —CH 2 morphilin-3-yl radical of formula (Q) wherein W is O, said 4-piperidine, 4-azepine, 1,4-cyclohexyl and —CH 2 morphilin-3-yl radicals being optionally substituted with one more substituents independently selected from fluorine, hydroxyl, C 1-4 -alkyl, C 1-4 -alkoxy, fluoro-C 1-4 -alkyl, and fluoro-C 1-4 -alkoxy.

11. A compound as claimed in claim 9 wherein R 2 is a 4-azepine radical of formula (N) wherein o is 2 and p is 2, a 1,4-cyclohexyl radical of formula (R) or a —CH 2 morphilin-3-yl radical of formula (Q) wherein W is O, said a 4-azepine, 1,4-cyclohexyl and —CH 2 morphilin-3-yl radicals being optionally substituted with one more substituents independently selected from fluorine, hydroxyl, C 1-4 -alkyl, C 1-4 -alkoxy, fluoro-C 1-4 -alkyl, and fluoro-C 1-4 -alkoxy.

12. A compound as claimed in claim 1 , wherein R 6 is selected from C 1-6 -alkyl, C 1-6 fluoroalkyl, C 1-2 -alkoxy-C 1-4 alkyl, C 3-5 cycloalkyl, C 3-5 fluorocycloalkyl, benzyl, alpha methyl-benzyl, and benzyl or alpha methyl-benzyl either of which being optionally ring-substituted by one or two substituents selected from halogen, C 1-4 -alkyl, and C 1-4 -alkoxy.

13. A compound having formula (IA):

wherein R 6 is

selected from C 1-6 -alkyl, C 3-5 -cycloalkyl, C 3-5 -cycloalkyl-C 1-4 -alkyl, heterocyclyl, heterocyclyl-C 1-4 -alkyl, C 6-10 -aryl-C 1-4 -alkyl, and C 6-10 -aryl, wherein

(i) said C 1-6 -alkyl, C 3-5 -cycloalkyl, heterocyclyl, or the C 1-6 -alkyl part of said heterocyclyl-C 1-4 -alkyl or C 6-10 -aryl-C 1-4 -alkyl, or the heterocyclyl part of said heterocyclyl-C 1-4 -alkyl is optionally substituted with one or more substituents independently selected from fluorine, hydroxyl, and C 1-4 -alkoxy, and

(ii) said C 6-10 -aryl or the C 6-10 -aryl part of said C 6-10 -aryl-C 1-4 -alkyl is optionally substituted with one more substituents independently selected from halogen, hydroxy, cyano, nitro, C 1-4 -alkyl, C 1-4 -alkoxy, fluoro-C 1-4 -alkyl, fluoro-C 1-4 -alkoxy, C 1-4 -alkoxy-C 1-4 -alkyl, and fluoro-C 1-4 -alkoxy-C 1-4 -alkyl; and

R 21 and R 22 are independently selected from hydrogen, halogen, C 1-6 -alkyl, C 1-6 fluoroalkyl, C 1-4 -alkoxy, C 1-2 -alkoxy-C 1-4 alkyl, C 3-5 cycloalkyl, C 3-5 fluorocycloalkyl, benzyl, alpha methyl-benzyl, and benzyl or alpha methyl-benzyl either of which being optionally ring-substituted by one or two substituents selected from halogen, C 1-4 -alkyl, and C 1-4 -alkoxy.

14. A compound as claimed in claim 13 wherein R 21 and R 22 are independently selected from hydrogen and methyl, and R 6 is isopropyl.

15. A pharmaceutical composition comprising a compound as claimed in claim 1 , together with one or more pharmaceutically acceptable carriers and/or excipients.

16. The pharmaceutical composition of claim 15 , the compound having formula (IA):

wherein R 6 is selected from C 1-6 -alkyl, C 3-5 -cycloalkyl, C 3-5 -cycloalkyl-C 1-4 -alkyl, heterocyclyl, heterocyclyl-C 1-4 -alkyl, C 6-10 -aryl-C 1-4 -alkyl, and C 6-10 -aryl, wherein

(i) said C 1-6 -alkyl, C 3-5 -cycloalkyl, heterocyclyl, or the C 1-6 -alkyl part of said heterocyclyl-C 1-4 -alkyl or C 6-10 -aryl-C 1-4 -alkyl, or the heterocyclyl part of said heterocyclyl-C 1-4 -alkyl is optionally substituted with one or more substituents independently selected from fluorine, hydroxyl, and C 1-4 -alkoxy, and

(ii) said C 6-10 -aryl or the C 6-10 -aryl part of said C 6-10 -aryl-C 1-4 -alkyl is optionally substituted with one more substituents independently selected from halogen, hydroxy, cyano, nitro, C 1-4 -alkyl, C 1-4 -alkoxy, fluoro-C 1-4 -alkyl, fluoro-C 1-4 -alkoxy, C 1-4 -alkoxy-C 1-4 -alkyl, and fluoro-C 1-4 -alkoxy-C 1-4 -alkyl; and

R 21 and R 22 are independently selected from hydrogen, halogen, C 1-6 -alkyl, C 1-6 fluoroalkyl, C 1-4 -alkoxy, C 1-2 -alkoxy-C 1-4 alkyl, C 3-5 cycloalkyl, C 3-5 fluorocycloalkyl, benzyl, alpha methyl-benzyl, and benzyl or alpha methyl-benzyl either of which being optionally ring-substituted by one or two substituents selected from halogen, C 1-4 -alkyl, and C 1-4 -alkoxy.

17. The pharmaceutical composition of claim 16 , wherein R 21 and R 22 are independently selected from hydrogen and methyl, and R 6 is isopropyl.