Pyrimidyl sulphone amide derivatives as chemokine receptor modulators

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

• wherein R1 is a group selected from C3-7carbocyclyl, C1-8alkyl, C2-6alkenyl and C2-6alkynyl;
• wherein the group is optionally substituted by 1, 2 or 3 substituents independently selected from fluoro, nitrile, —OR4, —NR5R6, —CONR5R6, —COOR7, —NR8COR9, —SR10, —SO2R10, —SO2NR5R6, —NR8SO2R9, phenyl or heteroaryl;
• wherein phenyl and heteroaryl are optionally substituted by 1, 2 or 3 substituents independently selected from halo, cyano, nitro, —OR4, —NR5R6, —CONR5R6, —COOR7, —NR8COR9, —SR10, —SO2R10, —SO2NR5R6, —NR8SO2R9, C1-6alkyl and trifluoromethyl;
• wherein R2 is C3-7carbocyclyl, optionally substituted by 1, 2 or 3 substituents independently selected from:
• (a) fluoro, —OR4, —NR5R6—CONR5R6, —COOR7, —NR8COR9, —SR10, —SO2R10, —SO2NR5R6, —NR8SO2R9;
• (b) a 3-8 membered ring optionally containing 1, 2 or 3 atoms selected from O, S, —NR8 and whereby the ring is optionally substituted by C1-3alkyl or fluoro;
• or
• (c) phenyl or heteroaryl, each of which is optionally substituted by 1, 2 or 3 substituents independently selected from halo, cyano, nitro, —OR4, —NR5R6, —CONR5R6, —NR8COR9, —SO2NR5R6, —NR8SO2R9, C1-6alkyl and trifluoromethyl;
• or R2 is a group selected from C1-8alkyl, C2-6alkenyl or C2-6alkynyl wherein the group is substituted by 1, 2 or 3 substituents independently selected from hydroxy, amino, C1-6alkoxy, C1-6alkylamino, di(C1-6alkyl)amino, N—(C1-6alkyl)-N-(phenyl)amino, N—C1-6alkylcarbamoyl, N,N-di(C1-6alkyl)carbamoyl, N—(C1-6alkyl)-N-phenyl)carbamoyl, carboxy, phenoxycarbonyl, —NR8COR9, —SO2R10, —SO2NR5R6 and —NR8SO2R9;
• wherein R3 is hydrogen or independently R2;
• R4 is hydrogen or a group selected from C1-6alkyl and phenyl, wherein the group is optionally substituted by 1 or 2 substituents independently selected from halo, phenyl, —OR11 and —NR12R13;
• R5 and R6 are independently hydrogen or a group selected from C1-6alkyl and phenyl wherein the group is optionally substituted by 1, 2 or 3 substituents independently selected from halo, phenyl, —OR14, —NR15R16, —COOR14, —CONR15R16, —NR15COR16, —SO2R10, —SONR15R16 and NR15SO2R16 or
• R5 and R6 together with the nitrogen atom to which they are attached form a 4- to 7-membered saturated heterocyclic ring system optionally containing a further heteroatom selected from oxygen and nitrogen atoms, which ring is optionally substituted by 1, 2 or 3 substituents independently selected from phenyl, —OR14, —COOR14, —NR15R16, —CONR15R16, —N15COR16, —SO2R10, —SONR15R16, NR15SO2R16 or C1-6alkyl (optionally substituted by 1 or 2 substituents independently selected from halo, —NR15R16 and —OR17 groups);
• R10 is hydrogen or a group selected from C1-6alkyl or phenyl, wherein the group is optionally substituted by 1, 2 or 3 substituents independently selected from halo, phenyl, —OR17 and —NR15R16;
• and
• each of R7, R8, R9, R11, R12, R13, R14 R15, R16, R17 is independently hydrogen, C1-6alkyl or phenyl;
• X is hydrogen, halo, cyano, nitro, hydroxy, C1-6alkoxy (optionally substituted by 1 or 2 substituents selected from halo, —OR11 and —NR12R13), —NR5R6, —COOR7, —NR8COR9, thio, C1-6alkylthio (optionally substituted by 1 or 2 substituents selected from halo, —OR17, —NR15R16), —SO2R10 or a group selected from C3-7carbocyclyl, C1-8alkyl, C2-6alkenyl or C2-6alkynyl, wherein the group is optionally substituted by 1, 2 or 3 substituents independently selected from halo, —OR4, —NR5R6, —CONR5R6, —COOR7, —NR8COR9, —SR10, —SO2R10, —SO2NR5R6 and —NR8SO2R9;
• Rx is trifluoromethyl, —NR5R6, phenyl, napthyl, monocyclic or bicyclic heteroaryl wherein a heteroring may be partially or fully saturated and one or more ring carbon atoms may form a carbonyl group, and wherein each phenyl or heteroaryl group is optionally substituted by 1, 2 or 3 substituents independently selected from halo, cyano, nitro, —OR4, —NR5R6, —CONR5R6, —COR7, —COOR7, —NR8COR9, —SR10, —SO2R10, —SO2NR5R6, —NR8SO2R9, C1-6alkyl or trifluoromethyl;
• or Rx is a group selected from C3-7carbocyclyl, C1-8alkyl, C2-6alkenyl and C2-6alkynyl whereby the group is optionally substituted by 1, 2 or 3 substituents independently selected from halo, —OR4, —NR5R6, —CONR5R6, —COR7, —COOR7, —NR8COR9, —SR10, —SO2R10, —SO2NR5R6, —NR8SO2R9, phenyl or heteroaryl;
• and wherein each phenyl or heteroaryl group is optionally substituted by 1, 2 or 3 substituents independently selected from halo, cyano, nitro, —OR4, —NR5R6, —CONR5R6, —COR7, —COOR7, —NR8COR9, —SR10, —SO2R10, —SO2NR5R6, —NR8SO2R9, C1-6alkyl or trifluoromethyl;
• or Rx and X together form a 4 to 8-membered sulfonamide ring optionally substituted by 1, 2 or 3 substituents independently selected from halo, —OR4, —NR5R6, —CONR5R6, —COOR7, —NR8COR9, —SR10, —SO2R10, —SO2NR5R6, —NR8SO2R9, phenyl or heteroaryl;
• wherein phenyl and heteroaryl are optionally substituted by 1, 2 or 3 substituents independently selected from halo, cyano, nitro, —OR4, —NR5R6, —CONR5R6, —COOR7, —NR8COR9, —SR10, —SO2R10, —SO2NR5R6, —NR8SO2R9, C1-6alkyl and trifluoromethyl.