Thiadiazoles AS CXC- and CC- chemokine receptor ligands

A compound of the formula:

• and the pharmaceutically acceptable salts thereof, wherein:
• A is selected from the group consisting of:
• wherein the above rings of said A groups are substituted with 1 to 6 substituents each independently selected from the group consisting of:
• R9 groups;
• wherein one or both of the above rings of said A groups are substituted with 1 to 6 substituents each independently selected from the group consisting of:
• R9 groups;
• wherein the above phenyl rings of said A groups are substituted with 1 to 3 substituents each independently selected from the group consisting of:
• R9 groups;
• and
• B is selected from the group consisting of
• n is 0 to 6;
• p is 1 to 5;
• X is O, NR18, or S;
• Z is 1 to 3;
• R2 is selected from the group consisting of:
• hydrogen, OH, —C(O)OH, —SH, —SO2NR13R14, —NHC(O)R13, —NHSO2NR13R14, —NHSO2R13, —NR13R14, —C(O)NR13R14, —C(O)NHOR13, —C(O)NR13OH, —S(O2)OH, —OC(O)R13, an unsubstituted heterocyclic acidic functional group, and a substituted heterocyclic acidic functional group;
• wherein there are 1 to 6 substituents on said substituted heterocyclic acidic functional group each substituent being independently selected from the group consisting of:
• R9 groups;
• each R3 and R4 is independently selected from the group consisting of:
• hydrogen, cyano, halogen, alkyl, alkoxy, cycloalkyl substituted with 1 to 4 alkyl groups wherein each alkyl group is independently selected, unsubstituted cycloalkyl, cycloalkyl substituted with 1 to 4 alkyl groups, —OH, —CF3, —OCF3, —NO2, —C(O)R13, —C(O)OR13, —C(O)NHR17, —C(O)NR13R14, —SO(t)NR13R14, —SO(t)R13, —C(O)NR13OR14, unsubstituted or substituted aryl, unsubstituted or substituted heteroaryl,
• wherein there are 1 to 6 substituents on said substituted aryl group and each substituent is independently selected from the group consisting of:
• R9 groups;
• and wherein there are 1 to 6 substituents on said substituted heteroaryl group and each substituent is independently selected from the group consisting of:
• R9 groups;
• or
• R3 is and R4 taken together with the carbons atoms to which they are bonded to in the the phenyl B substituent
• form a fused ring of the formula:
• wherein Z1 or Z2 is an unsubstituted or substituted saturated heterocyclic ring (preferably a 4 to 7 membered heterocyclic ring), said ring Z1 or Z2 optionally containing one additional heteroatom selected from the group consisting of:
• O, S and NR18;
• wherein there are 1 to 3 substituents on said ring Z1 or Z2, and each substituent is independently selected from the group consisting of:
• alkyl, aryl, hydroxy, hydroxyalkyl, alkoxy, alkoxyalkyl, arylalkyl, fluoroalkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, amino, —C(O)OR5, —C(O)NR5R6, —SOtNR5R6, —C(O)R15, —SO2R15 provided that R15 is not H, —NHC(O)NR15R16, —NHC(O)OR15, halogen, and a heterocycloalkenyl group;
• each R5 and R6 are the same or different and are independently selected from the group consisting of hydrogen, halogen, alkyl, alkoxy, —CF3, —OCF3, —NO2, —C(O)R13—C(O)OR13, —C(O)NR13R14, —SO(t)NR13R14, —C(O)NRO13OR14, cyano, unsubstituted or substituted aryl, and unsubstituted or substituted heteroaryl group;
• wherein there are 1 to 6 substituents on said substituted aryl group and each substituent is independently selected from the group consisting of:
• R9 groups;
• and wherein there are 1 to 6 substituents on said substituted heteroaryl group and each substituent is independently selected from the group consisting of:
• R9 groups;
• each R7 and R8 is independently selected from the group consisting of:
• H, unsubstituted or substituted alkyl, unsubstituted or substituted aryl, unsubstituted or substituted heteroaryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heteroarylalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted cycloalkylalkyl, —CO2R13, —CONR13R14, alkynyl, alkenyl, and cycloalkenyl;
• and wherein there are one or more substituents on said substituted R7 and R8 groups, wherein each substitutent is independently selected from the group consisting of:
• a) halogen,
• b) —CF3,
• c)—COR13,
• d) —OR13,
• e) —NR13R14,
• f) —NO2,
• g) —CN,
• h) —SO2OR13,
• i) —Si(alkyl)3, wherein each alkyl is independently selected,
• j) —Si(aryl)3, wherein each alkyl is independently selected,
• k) —(R13)2R14Si, wherein each R13 is independently selected,
• l) —CO2R13,
• m) —C(O)NR3R14,
• n) —SO2NR3R14,
• o) —SO2R13,
• p) —C(O)R13,
• q) —OC(O)NR13R14,
• r) —NR13C(O)R14, and
• s) —NR13CO2R14;
• (fluoroalkyl is one non-limiting example of an alkyl group that is substituted with halogen);
• R8a is selected from the group consisting of:
• hydrogen, alkyl, cycloalkyl and cycloalkylalkyl;
• each R9 is independently selected from the group consisting of:
• a) —R13,
• b) halogen,
• c) —CF3,
• d) —COR13,
• e) —OR,
• f) —NR13R14,
• g) —NO2,
• h) —CN,
• i) —SO2R13,
• j) —SO2NR13R14,
• k) —NR13COR14,
• l)—CONR13R14,
• m) —NR13CO2R14,
• n) —CO2R13,
• p) alkyl substituted with one or more —OH groups,
• q) alkyl substituted with one or more —NR13R14 group, and
• r) —N(R13)SO2R14;
• each R10 and R11 is independently selected from the group consisting of R13, halogen, —CF3, —OCF3, —NR13R14, —NR13C(O)NR13R14, —OH, —C(O)OR13, —SH, —SO(t)NR13R14, —SO2R13, —NHC(O)R13, —NHSO2NR13R14, —NHSO2R13, —C(O)NR13R14, C(O)NR13OR14, —OC(O)R13 and cyano;
• R12 is selected from the group consisting of:
• hydrogen, —C(O)OR13, unsubstituted or substituted aryl, unsubstituted or substituted heteroaryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted alkyl, unsubstituted or substituted cycloalkylalkyl, and unsubstituted or substituted heteroarylalkyl group;
• wherein there are 1 to 6 substituents on the substituted R12 groups and each substituent is independently selected from the group consisting of:
• R9 groups;
• each R13 and R14 is independently selected from the group consisting of:
• H, unsubstituted or substituted alkyl, unsubstituted or substituted cyanoalkyl, unsubstituted or substituted aryl, unsubstituted or substituted heteroaryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heteroarylalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted cyanocycloalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heterocyclic, unsubstituted or substituted fluoroalkyl, and unsubstituted or substituted heterocycloalkylalkyl (wherein “heterocyloalkyl” means heterocyclic);
• wherein there are 1 to 6 substituents on said substituted R13 and R14 groups and each substituent is independently selected from the group consisting of:
• alkyl, —CF3, —OH, alkoxy, aryl, arylalkyl, fluroalkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, —N(R40)2, —C(O)OR15, —C(O)NR15R16, —S(O)tNR15R16, —C(O)R15, halogen, —NHC(O)NR15R16 and —SO2R15 provided that R15 is not H;
• and provided that for the substituted cyanoalkyl and the substituted cyanocycloalkyl moieties the carbon atom to which the cyano group is bound to does not also have bound to said carbon atom a substituent selected from the group consisting of:
• —OH, alkoxy, —N(R40)2, halogen and —NHC(O)NR15R16;
• or
• R13 and R14 taken together with the nitrogen they are attached to in the groups —C(O)NR13R14 and —SO2NR13R14 form an unsubstituted or substituted saturated heterocyclic ring, said ring optionally containing one additional heteroatom selected from the group consisting of:
• O, S and NR18;
• wherein there are 1 to 3 substituents on the substituted cyclized R13 and R14 groups and each substituent is independently selected from the group consisting of:
• CN, alkyl, cyanoalkyl, aryl, hydroxy, hydroxyalkyl, alkoxy, alkoxyalkyl, arylalkyl, fluoroalkyl, cycloalkyl, cyanocycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, amino, —C(O)OR15, —C(O)NR15R16, —SOtNR15R16, —C(O)R15, —SO2R15 (provided that R15 is not H), —NHC(O)NR15R16, —NHC(O)OR15, halogen, and a heterocycloalkenyl group;
• and provided that the carbon atom to which the cyano group is bound to does not also have bound to said carbon atom a substituent selected from the group consisting of:
• hydroxy, alkoxy, amino, halogen, —NHC(O)NR15R16 and —NHC(O)OR15;
• each R15 and R16 is independently selected from the group consisting of:
• H, alkyl, aryl, arylalkyl, cycloalkyl and heteroaryl;
• R17 is selected from the group consisting of:
• —SO2alkyl, —SO2aryl, —SO2cycloalkyl, and —SO2heteroaryl;
• R18 is selected from the group consisting of:
• H, alkyl, aryl, heteroaryl, —C(O)R19, —SO2R19 and —C(O)NR19R20;
• each R19 and R20 is independently selected from the group consisting of:
• alkyl, aryl and heteroaryl;
• R30 is selected from the group consisting of:
• alkyl, cycloalkyl, —CN, —NO2, or —SO2R15 provided that R15 is not H;
• each R31 is independently selected from the group consisting of:
• unsubstituted alkyl, unsubstituted or substituted aryl, unsubstituted or substituted heteroaryl and unsubstituted or substituted cycloalkyl;
• wherein there are 1 to 6 substituents on said substituted R31 groups and each substituent is independently selected from the group consisting of:
• alkyl, halogen and —CF3;
• each R40 is independently selected from the group consisting of:
• H, alkyl and cycloalkyl;
• and
• t is 0, 1 or 2.