What is claimed is:
1. A method of treating a disease associated with aberrant leukocyte recruitment and/or activation comprising administering to a subject in need thereof a therapeutically effective amount of a compound represented by the following structural formula:
z L N M ;
and physiologically acceptable salts thereof, wherein:
Z is a cycloalkyl or non-aromatic heterocyclic ring group fused to a pyridine ring and to a carbocyclic aromatic or heteroaromatic ring, wherein each ring in Z is independently substituted or unsubstituted;
L is a C1-C1B substituted or unsubstituted hydrocarbyl group ,-
M is >NR2 or >CRXR2;
R1 is -H, -OH, an aliphatic group, -0- (aliphatic group) , -O- (substituted aliphatic group) , -SH,
-S- (aliphatic group) , -S- (substituted aliphatic group) , -OC (0) - (aliphatic group), -0-C (0) - (substituted aliphatic group) , -CN, -C00H, -C0-NR3R4 or -NR3R4; and
R2 is -H, -OH, an acyl group, a substituted acyl group, -NR5Rδ, an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group, a benzyl group, a substituted benzyl group, a non-aromatic heterocyclic group or a substituted non-aromatic heterocyclic group; wherein:
R3, R4, R5 and R6 are independently -H, an acyl group, a substituted acyl group, an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group, a benzyl group, a substituted benzyl group, a non-aromatic heterocyclic group or a substituted non-aromatic heterocyclic group; or
R1 and R2, R3 and R4, or R5 and R6 taken together with the atom to which they are bonded, form a substituted or unsubstituted non-aromatic carbocyclic or heterocyclic ring.
2. The method of Claim 1 wherein L is represented by the following structural formula:
Y- (CH2)n- •X
wherein:
Y is a single or double covalent bond, -0- , -CO- or =CH- ; n is an integer from one to about five; and
X is a covalent bond or -CO- .
3. The method of Claim 2 wherein X and Y are each a covalent bond.
4. The method of Claim 3 wherein Z is represented by the following structural formula:
wherein:
Ring A and Ring B are individually substituted or unsubstituted; and
Ring C is a substituted or unsubstituted C6, C7 or C8 non-aromatic carbocyclic ring or a substituted or unsubstituted non-aromatic heterocyclic ring.
5. The method of Claim 4 wherein Z is represented by a structural formula selected from:
wherein:
Xx is a covalent bond d,, -S-, — H2 - , - H — H2 — , — H — , —S - H2 - , -O- H2— , - CH2-0-, -NRC-CH2-, -CH2-NRC-, -S0-CH2-, -CH2-SO-, -S(0)2 - CH2 - , -CH2-S(0)2-, -CH=CH-, -Nrc-CO- or -CO-NRc- ;
Rc is hydrogen, an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group, a benzyl group or a substituted benzyl group;
W is -H, an electron withdrawing group, -O^-NR^R12, -CH2-OR11, -CH=NH, -CHs-NH-CO-NR^R12, -CH2-0-CO-NR**R12 or -CH2-NHC (0) -O-R11; wherein:
R11 and R12 are independently -H, an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group or a non-aromatic heterocyclic group; or
R11 and R12, taken together with the nitrogen atom to which they are bonded, form a non-aromatic heterocyclic ring;
n is an integer from 2-5;
Ring B is substituted with R8 and R9, wherein R8 and R9 are independently -H, a halogen, alkoxy or alkyl, or, taken together with Ring B, form a naphthyl group;
M is >N (alkanoyl) , >N(aroyl), >N (aralkoyl) , >N(alkyl), >N(aralkyl), >N (cycloalkyl) , >C (OH) (aryl) or >CH (heteroaryl) .
6 . The method of Claim 5 wherein Rc is - (CH2 ) s- COOR30 , - (CH2 ) s- C (0) -NR31R32 or - ( CH2 ) S-NHC (0) -O-R30 ; wherein : s is an integer from zero to about 3;
R30, R31 or R32 are independently -H, an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group or a non-aromatic heterocyclic group; or
R31 and R32, taken together with the nitrogen atom to which they are bonded, form a non-aromatic heterocyclic ring.
7. The method of Claim 2 wherein X is a covalent bond and Y is -CO- .
8. A method of treating a disease associated with aberrant leukocyte recruitment and/or activation comprising administering to a subject in need thereof a therapeutically effective amount of a compound represented by the following structural formula:
and physiologically acceptable salts thereof, wherein:
Y is a single covalent bond; n is an integer from one to about five;
X is a single covalent bond; and M is >NR2 or >CRXR2;
R1 is -H, -OH, an aliphatic group, -O- (aliphatic group) , -0- (substituted aliphatic group) , -SH, -S- (aliphatic group) , -S- (substituted aliphatic group) , -OC(O) - (aliphatic group), -O-C (0) - (substituted aliphatic group), -CN, -C00H, -CO-NR3R4 or -NR3R4; and R2 is -H, -OH, an acyl group, a substituted acyl group, -NR5R6, an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group, a benzyl group, a substituted benzyl group, a non-aromatic heterocyclic group or a substituted non-aromatic heterocyclic group; wherein: R3, R4, Rs and R6 are independently -H, an acyl group, a substituted acyl group, an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group, a benzyl group, a substituted benzyl group, a non-aromatic heterocyclic group or a substituted non-aromatic heterocyclic group; or
R1 and R2, R3 and R4, or R5 and Rs taken together with the atom to which they are bonded, form a substituted or unsubstituted non-aromatic carbocyclic or heterocyclic ring;
Z is represented by a structural formula selected from:
wherein:
Ring B and Ring C are independently substituted or unsubstituted;
Xx is a covalent bond, -S-, -CH2-, -CH2-CH2-, -CH2-S-, -S-CH2-, -0-CH2-, -CH2-0-, -NRC-CH2-, -CH2-NRC-, -S0-CH2-, -CH2-SO-, -S(0)2-CH2-, -CH2-S(0)2-, -CH=CH-, -Nrc-C0-, -CO-NRc- ; Rc is hydrogen, an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group, a benzyl group or a substituted benzyl group; and
W is -H or an electron withdrawing group.
. The method of Claim 8 wherein Ring B is substituted with -OH, a halogen, -0- (aliphatic group) ,
-0- (substituted aliphatic group) , -0- (aromatic group) , -0- (substituted aromatic group) , an electron withdrawing group, - (0) u- (CH2) t-COOR20,
- (0 ) u- ( CH2 ) t - C ( 0) -NR 1R22 or - (0) u- ( CH2 ) C -NHC ( 0) -O -R20 ; wherein : u i s zero or one ; t is an integer from zero to about 3 ; R20, R21 or R22 are independently -H, an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group or a non-aromatic heterocyclic group; or
R21 and R22, taken together with the nitrogen atom to which they are bonded, form a non-aromatic heterocyclic ring.
10. The method of Claim 8 wherein Rc is - (CH2) s-COOR30,
- (CH2)s-C(0) -NR31R32 or - (CH2) S-NHC (0) -O-R30 ; wherein: s is an integer from one to about 3 ; R30, R31 or R32 are independently -H, an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group or a non-aromatic heterocyclic group; or
R31 and R3 , taken together with the nitrogen atom to which they are bonded, form a non-aromatic heterocyclic ring.
11. The method of Claim 9 wherein Ring B is substituted para to the carbon atom of Ring B which is bonded to Xx
in Ring C, and Z represented by a structural formula selected from:
wherein R40 is -OH, halogen, aliphatic group, substituted aliphatic group, -0- (aliphatic group), -0- (substituted aliphatic group) , -0- (aromatic group) , -0- (substituted aromatic group) , an electron withdrawing group, - (0) u- (CH2) t-COOR20,
- (0)..- (CH2)t-0C(0)R20, - (0)u- (CH2)t-C(0) -NR21R22 or
- (0)u- (CH2)t-NHC(0) -O-R20; wherein: u is zero or one; t is an integer from zero to about 3;
R20, R21 or R22 are independently -H, an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group or a non-aromatic heterocyclic group; or
R21 and R22, taken together with the nitrogen atom to which they are bonded, form a non-aromatic heterocyclic ring.
12. The method of Claim 11 wherein Rc is - (CH2) s-COOR30, - (CH2)ε-C(0) -NR31R32 or - (CH2) S-NHC (0) -O-R30; wherein: s is an integer from one to about 3 ; R30, R31 or R32 are independently -H, an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group or a non-aromatic heterocyclic group; or
R31 and R32, taken together with the nitrogen atom to which they are bonded, form a non-aromatic heterocyclic ring.
13. The method of Claim 11 wherein R40 -0-CH3.
14. The method of Claim 13 wherein R1 is -OH.
15. The method of Claim 13 wherein M is >C(0H)R2 and n is three .
16. The method of Claim 15 wherein: W is -CN; and X1 is -CH2-0-, -CH2-CH2- or -CH2-S- .
17. The method of Claim 16 wherein R2 is a substituted or unsubstituted aromatic group.
18. The method of Claim 17 wherein R2 is an aromatic group that is substituted with a halogen.
19. The method of Claim 18 wherein R2 is a 4-chlorophenyl group .
0. A method of treating a disease associated with aberrant leukocyte recruitment and/or activation comprising administering to a subject in need thereof a therapeutically effective amount of a compound represented by the following structural formula:
and physiologically acceptable salts thereof, wherein:
Y is a single covalent bond; n is an integer from one to about five;
X is a single covalent bond; and M is >NR2 or >CR*R2;
R1 is -H, -OH, an aliphatic group, -O- (aliphatic group) , -0- (substituted aliphatic group) , -SH, -S- (aliphatic group) , -S- (substituted aliphatic group) , -0C(0) - (aliphatic group) , -O-C (O) - (substituted aliphatic group) , -CN, -COOH, -CO-NR3R4 or -NR3R4; and R2 is -H, -OH, an acyl group, a substituted acyl group, -NRSRS, an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group, a benzyl group, a substituted benzyl group, a non-aromatic heterocyclic group or a substituted non-aromatic heterocyclic group; wherein: R3, R4, R5 and R6 are independently -H, an acyl group, a substituted acyl group, an aliphatic group, a
substituted aliphatic group, an aromatic group, a substituted aromatic group, a benzyl group, a substituted benzyl group, a non-aromatic heterocyclic group or a substituted non-aromatic heterocyclic group; or
R1 and R2, R3 and R4, or R5 and R6 taken together with the atom to which they are bonded, form a substituted or unsubstituted non-aromatic carbocyclic or heterocyclic ring;
Z is represented by a structural formula selected from:
wherein:
Ring B and Ring C are independently substituted or unsubstituted;
X-L is a covalent bond, -S-, -CH2-, -CH2-CH2-, -CH2-S-, -S-CH2-, -0-CH2-, -CH2-0-, -NRC-CH2-, -CH2-NRC-, -SO-CH2-, -CH2-S0-, -S(0)2-CH2-, -CH2-S(0)2-, -CH=CH-, -Nr.-CO-, -CO-NR- ;
Rc is hydrogen, an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group, a benzyl group or a substituted benzyl group,- and W is -O^-NR^R12, -CH2-0Ru, -CH2-NH-CO-NRnR12,
-CT^-O-CO-NR^R12 or -CH2-NHC (0) -O-R11;
R11 and R12 are independently -H, an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group or a non-aromatic heterocyclic group; or
R11 and R12, taken together with the nitrogen atom to which they are bonded, form a non-aromatic heterocyclic ring.
21. The method of Claim 20 wherein Ring B is substituted with -OH, a halogen, -0- (aliphatic group) ,
-O- (substituted aliphatic group) , -0- (aromatic group) , -0- (substituted aromatic group) , an electron withdrawing group, - (0) u- (CH2) t-COOR20, - (0)u- (CH2)t-OC(0)R20, - (0)u- (CH2)t-C(0) -NR21R22 or - (0)u- (CH2) t-NHC(0) -O-R20; wherein: u is zero or one; t is an integer from zero to about 3; R20, R21 or R22 are independently -H, an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group or a non-aromatic heterocyclic group; or
R21 and R22 , taken together with the nitrogen atom to which they are bonded, form a non-aromatic heterocyclic ring.
2 . The method of Claim 20 wherein Rc i s - ( CH2 ) s- COOR30 , - ( CH2 ) s -C (0) -NR31R32 or - ( CH2 ) S-NHC ( 0) - O-R30 ; wherein : s is an integer from one to about 3 ;
R30, R31 or R32 are independently -H, an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group or a non-aromatic heterocyclic group; or
R31 and R32, taken together with the nitrogen atom to which they are bonded, form a non-aromatic heterocyclic ring.
23. The method of Claim 21 wherein Ring B is substituted para to the carbon atom of Ring B which is bonded to Xx in Ring C, and Z is represented by a structural formula selected from:
wherein R40 is -OH, halogen, aliphatic group, substituted aliphatic group, -0- (aliphatic group) , -0- (substituted aliphatic group) , -0- (aromatic group) , -0- (substituted aromatic group) , an electron withdrawing group, - (0)u- (CH2) t-COOR20,
- (0)u- (CH2)t-OC(0)R20,- (0)u- (CH2)t-C(0) -NR21R22 or
- (0)u- (CH2)t-NHC(0) -O-R20; wherein: u is zero or one; t is an integer from zero to about 3 ; R20, R21 or R22 are independently -H, an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group or a non-aromatic heterocyclic group; or
R21 and R22, taken together with the nitrogen atom to which they are bonded, form a non-aromatic heterocyclic ring.
24. The method of Claim 23 wherein Rc is - (CH2) s-COOR30,
- (CH2)s-C(0) -NR31R32 or - (CH2) S-NHC (O) -O-R30; wherein: s is an integer from one to about 3; R30, R31 or R32 are independently -H, an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group or a non-aromatic heterocyclic group; or
R31 and R32, taken together with the nitrogen atom to which they are bonded, form a non-aromatic heterocyclic ring.
25. The method of Claim 23 wherein R40 is -0-CH3.
26. The method of Claim 25 wherein R1 is -OH.
27. The method of Claim 25 wherein M is >C(0H)R2 and n is three.
28. The method of Claim 27 wherein Xx is -CH2-0, -CH2-CH2 or -CH2-S-
29. The method of Claim 28 wherein R2 is a substituted or unsubstituted aromatic group.
30. The method of Claim 29 wherein R2 is an aromatic group that is substituted with a halogen.
31. The method of Claim 30 wherein R2 is a 4-chlorophenyl group .
32. A method of treating a disease associated with aberrant leukocyte recruitment and/or activation comprising administering to a subject in need thereof a therapeutically effective amount of a compound represented by the following structural formula:
-Y (CH2)n X N M
and physiologically acceptable salts thereof, wherein:
Y is a single covalent bond; n is an integer from one to about five; X is a single covalent bond; and M is >NR2 or >CR1R2;
R1 is -H, -OH, an aliphatic group, -0- (aliphatic group) , -O- (substituted aliphatic group) , -SH,
-S- (aliphatic group) , -S- (substituted aliphatic group) , -OC (O) - (aliphatic group), -O-C (0) - (substituted aliphatic group) , -CN, -COOH, -CO-NR3R4 or -NR3R4; and R2 is -H, -OH, an acyl group, a substituted acyl group, -NRSRS, an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group, a benzyl group, a substituted benzyl group, a non-aromatic heterocyclic group or a substituted non-aromatic heterocyclic group; wherein: R3, R4, R5 and R6 are independently -H, an acyl group, a substituted acyl group, an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group, a benzyl group, a substituted benzyl group, a non-aromatic heterocyclic group or a substituted non-aromatic heterocyclic group; or
R1 and R , R3 and R4, or R5 and R6 taken together with the atom to which they are bonded, form a substituted or unsubstituted non-aromatic carbocyclic or heterocyclic ring;
Z is represented by a structural formula selected from:
Ring B is a substituted or unsubstituted carbocyclic aromatic or heteroaryl group;
Xλ is a covalent, -S-, -CH2-, -CH2-CH2-, -CH2-S-, -S-CH2-, -0-CH2-, -CH2-0-, -NRC-CH2-, -CH2-NRC-, -SO-CH2-, -CH2-SO-, -S(0)2-CH2-, -CH2-S(0)2-, -CH=CH-, -NRc-C0- or -CO-NRc- ,- wherein:
Rc is hydrogen, an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group, a benzyl group or a substituted benzyl group; and
W is -H, -C^-NR^R12, -CT^-OR11, -O^-NH-CO-NR^R12, -C^-O-CO-NR'-R12 , -CH2-NHC(0) -O-R11 or an electron withdrawing group; R11 and R12 are independently -H, an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group or a non-aromatic heterocyclic group,- or
R11 and R12 , taken together with the nitrogen atom to which they are bonded, form a non-aromatic heterocyclic ring.
33. The method of Claim 32 wherein Ring B is substituted with -OH, a halogen, -0- (aliphatic group) , -0- (substituted aliphatic group) , -O- (aromatic group) , -0- (substituted aromatic group) , an electron withdrawing group, - (0) u- (CH2) t-C00R2C, - (0)u- (CH2)t-C(0) -NR21R22 or - (0) u- (CH2) C-NHC (0) -O-R20; wherein: u is zero or one;
t is an integer from zero to about 3 ;
R20, R21 or R22 are independently -H, an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group or a non-aromatic heterocyclic group; or
R21 and R22, taken together with the nitrogen atom to which they are bonded, form a non-aromatic heterocyclic ring.
34. The method of Claim 32 wherein Rc is - (CH2) Ξ-COOR30, - (CH2) S-C(0) -NR31R32 or - (CH2) S-NHC (O) -O-R30; wherein: s is an integer rom one to about 3 ;
R30, R31 or R32 are independently -H, an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group or a non-aromatic heterocyclic group; or
R31 and R32, taken together with the nitrogen atom to which they are bonded, form a non-aromatic heterocyclic ring.
35. The method of Claim 32 wherein R1 is -OH.
36. The method of Claim 32 wherein M is >C(OH)R2 and n is three .
37. The method of Claim 36 wherein R2 is a substituted or unsubstituted aromatic group.
38. The method of Claim 37 wherein R2 is an aromatic group that is substituted with a halogen.
39. The method of Claim 38 wherein R2 is a 4-chlorophenyl group .
40. A compound represented by the following structural formula :
/ \
L- ■N ϊ M ;
\ /
and physiologically acceptable salts thereof, wherein:
L is a C-L-C^ hydrocarbyl group;
M is >N (alkanoyl) , >N(aroyl), >N (aralkoyl) , >N (alkyl), >N(aralkyl), >N (cycloalkyl) , >C(0H) (aryl) or >CH (heteroaryl) ;
Z is represented by a structural formula selected from:
X-L is a covalent bond, -S-, -CH2-, -CH2-CH2-, -CH2-S-, -S-CH2-, -0-CH2-, -CH2-0-, -NRC-CH2-, -CH2-NRC-, -SO-CH2-, -CH2-SO-, -S(0)2-CH2-, -CH2-S(0)2-, -CH=CH-, -Nrc-CO- or -CO-NRc- ;
Rc is hydrogen, an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group, a benzyl group or a substituted benzyl group; W is -H, -CN, -CH=NH, alkylsulfonyl , carboxamido or carboxyalkyl ; and
Ring A, Ring B and Ring C are independently substituted or unsubstituted.
41. The compound of Claim 40 wherein Ring B is substituted with R8 and R9, wherein R8 and R9 are independently -H, a halogen, alkoxy or alkyl, or, taken together with ring B, form a naphthyl group.
42. The compound of Claim 40 wherein Rc is - (CH2) s-COOR30, - (CH2)s-C(0) -NR31R32 or - (CH2) S-NHC (0) -O-R30 ; wherein: s is an integer from one to about 3 ; R30, R31 or R32 are independently -H, an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group or a non-aromatic heterocyclic group; or
R31 and R32, taken together with the nitrogen atom to which they are bonded, form a non-aromatic heterocyclic ring.
3. A compound represented by the following structural formula:
-(CH2)n X- M
and physiologically acceptable salts thereof, wherein:
Y is a single covalent bond; n is an integer from one to about five; X is a covalent bond; and M is >NR2 or >CR*R2; R1 is -H, -OH, an aliphatic group, -0- (aliphatic group) , -0- (substituted aliphatic group) , -SH, -S- (aliphatic group) , -S- (substituted aliphatic group) , -OC (O) - (aliphatic group), -O-C (O) - (substituted aliphatic group) , -CN, -COOH, -CO-NR3R4 or -NR3R4; and R2 is -H, -OH, an acyl group, a substituted acyl group, -NR5R6, an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group, a benzyl group, a substituted benzyl group, a non-aromatic heterocyclic group or a substituted non-aromatic heterocyclic group; wherein: R3, R4, R5 and R6 are independently -H, an acyl group, a substituted acyl group, an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group, a benzyl group, a substituted benzyl group, a non-aromatic heterocyclic
group or a substituted non-aromatic heterocyclic group; or
R1 and R2, R3 and R4, or R5 and R6 taken together with the atom to which they are bonded, form a substituted or unsubstituted non-aromatic carbocyclic or heterocyclic ring;
Z is represented by a structural formula selected from:
wherein:
Ring B is substituted or unsubstituted;
Xx is a covalent bond, -S-, -CH2-, -CH2-CH2-,
-CH,-S- -S-CH, -O-CH, -CH2-0- -NR„-CH, -CH2-NRC
-SO-CH2-, -CHj-SO-, -S(0)2-CH2-, -CH2-S(0)2-, ■CH=CH-, -Nrc-CO-, -C0-NRc- ;
Rc is hydrogen, an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group, a benzyl group or a substituted benzyl group ; and
W is -H or an electron withdrawing group.
4. The compound of Claim 43 wherein Ring B is substituted with -OH, a halogen, -0- (aliphatic group) ,
-0- (substituted aliphatic group) , -0- (aromatic group) , -0- (substituted aromatic group) , an electron withdrawing group, - (0) u- (CH2) t-COOR20,
- (0)u- (CH2)t-OC(0)R20, - (0)u- (CH2)t-C(0) -NR21R22 or
- (0)u- (CH2) t-NHC(0) -O-R20; wherein: u is zero or one; t is an integer from zero to about 3 ; R20, R21 or R22 are independently -H, an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group or a non-aromatic heterocyclic group; or
R21 and R22, taken together with the nitrogen atom to which they are bonded, form a non-aromatic heterocyclic ring.
45. The compound of Claim 43 wherein Rc is - (CH2) s-COOR30,
- (CH2)s-C(0) -NR31R32 or - (CH2) S-NHC (0) -O-R30; wherein: s is an integer from one to about 3 ; R30, R31 or R32 are independently -H, an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group or a non-aromatic heterocyclic group; or
R31 and R32, taken together with the nitrogen atom to which they are bonded, form a non-aromatic heterocyclic ring.
46. The compound of Claim 44 wherein Ring B is substituted para to the carbon atom of Ring B which is bonded to Xx
in Ring C, and Z is represented by a structural formula selected from:
wherein R40 is -OH, halogen, aliphatic group, substituted aliphatic group, -0- (aliphatic group) , -0- (substituted aliphatic group) , -O- (aromatic group) , -0- (substituted aromatic group) , an electron withdrawing group, - (0) u- (CH2) t-COOR20,
- (0)u- (CH2)t-OC(0)R2°, - (0)u- (CH2)t-C(0) -NR21R22 or
- (0)u- (CH2)t-NHC(0) -O-R20; wherein: u is zero or one; t is an integer from zero to about 3;
R2 or R are independently -H, an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group or a non-aromatic heterocyclic group; or
R21 and R22, taken together with the nitrogen atom to which they are bonded, form a non-aromatic heterocyclic ring.
47. The compound of Claim 46 wherein Rc is - (CH2) s-COOR30, - (CH2)s-C(0) -NR31R32 or - (CH2) S-NHC (0) -O-R30; wherein: s is an integer from one to about 3 ; R30, R31 or R32 are independently -H, an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group or a non-aromatic heterocyclic group; or
R31 and R32, taken together with the nitrogen atom to which they are bonded, form a non-aromatic heterocyclic ring.
48. The compound of Claim 46 wherein R40 is -0-CH3.
49. The compound of Claim 48 wherein R1 is -OH.
50. The compound of Claim 48 wherein M is >C(OH)R2 and n is three .
51. The compound of Claim 50 wherein: W is -CN; and Xj. is -CH2-0-, -CH2-CH2- or -CH2-S-.
52. The compound of Claim 51 wherein R2 is a substituted or unsubstituted aromatic group.
53. The compound of Claim 52 wherein R2 is an aromatic group that is substituted with a halogen.
54. The compound of Claim 53 wherein R2 is a 4-chlorophenyl group .
5. A compound represented by the following structural formula :
-(CH2)n X- M
and physiologically acceptable salts thereof, wherein:
Y is a single covalent bond; n is an integer from one to about five; X is a single covalent bond; and M is >NR2 or >CR1R2; R1 is -H, -OH, an aliphatic group, -0- (aliphatic group) , -O- (substituted aliphatic group) , -SH, -S- (aliphatic group) , -S- (substituted aliphatic group) , -OC (O) - (aliphatic group) , -O-C (0) - (substituted aliphatic group) , -CN, -COOH, -CO-NR3R4 or -NR3R4; and R2 is -H, -OH, an acyl group, a substituted acyl group, -NR5R6, an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group, a benzyl group, a substituted benzyl group, a non-aromatic heterocyclic group or a substituted non-aromatic heterocyclic group,- wherein: R3, R4, R5 and Rs are independently -H, an acyl group, a substituted acyl group, an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group, a benzyl group, a substituted benzyl group, a non-aromatic heterocyclic
group or a substituted non-aromatic heterocyclic group; or
R1 and R2, R3 and R4, or Rs and R6 taken together with the atom to which they are bonded, form a substituted or unsubstituted non-aromatic carbocyclic or heterocyclic ring;
Z is represented by a structural formula selected from:
wherein:
Ring B is substituted or unsubstituted;
Xj is a covalent bond, -S-, -CH2~, -CH2-CH2-,
-CH2 -S - , - S - CH2 -O-CH,-, -CH2-0- -NR„-CH, -CH2-NRC
-SO-CH2-, -CH2-SO-, -S(0)2-CH2-, -CH2-S(0)2-, -CH=CH-, -Nrc-CO-, -CO-NRc- ;
Rc is hydrogen, an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group, a benzyl group or a substituted benzyl group ,- and
W is -CH2-NR**R12, -CH2-0R , -CH^NH-CO-NR^R12, -CH^O-CO-NR^R12 or -CH2-NHC (0) -O-R11;
R11 and R12 are independently -H, an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group or a non-aromatic heterocyclic group;
R11 and R12, taken together with the nitrogen atom to which they are bonded, form a non-aromatic heterocyclic ring.
56. The compound of Claim 55 wherein Ring B is substituted with -OH, a halogen, -O- (aliphatic group) , -0- (substituted aliphatic group) , -0- (aromatic group) , -0- (substituted aromatic group) , an electron withdrawing group, - (0) u- (CH2) t-COOR20, - (0)u- (CH2)t-OC(0)R20, - (0)u- (CH2)t-C(0) -NR21R22 or - (0)u- (CH2) t-NHC(0) -0-R20; wherein: u is zero or one; t is an integer from zero to about 3 ; R20, R21 or R22 are independently -H, an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group or a non-aromatic heterocyclic group; or
R21 and R22, taken together with the nitrogen atom to which they are bonded, form a non-aromatic heterocyclic ring.
57. The compound of Claim 55 wherein Rc is - (CH2) s-C00R , - (CH2)s-C(0) -NR31R32 or - (CH2) S-NHC (0) -O-R30; wherein: s is an integer from one to about 3;
R30, R31 or R32 are independently -H, an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group or a non-aromatic heterocyclic group; or
R31 and R32, taken together with the nitrogen atom to which they are bonded, form a non- aromatic heterocyclic ring.
The compound of Claim 56 wherein Ring B is substituted para to the carbon atom of Ring B which is bonded to X3 in Ring C, and Z is represented by a structural formula selected from:
wherein R40 is -OH, halogen, aliphatic group, substituted aliphatic group, -O- (aliphatic group), -0- (substituted aliphatic group) , -0- (aromatic group) , -0- (substituted aromatic group) , an electron withdrawing group, - (O) u- (CH2) t-COOR20,
- (0)u- (CH2)t-OC(0)R20, - (0)u-(CH2)t-C(0) -NR21R22 or
- (0)u- (CH2)t-NHC(0) -O-R20; wherein: u is zero or one;
t is an integer from zero to about 3;
R20, R21 or R22 are independently -H, an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group or a non-aromatic heterocyclic group; or
R21 and R22, taken together with the nitrogen atom to which they are bonded, form a non-aromatic heterocyclic ring.
59. The compound of Claim 58 wherein Rc is - (CH2) s-COOR30, - (CH2)s-C(0) -NR31R32 or - (0) u- (CH2) t-NHC (0) -O-R20; wherein: s is an integer from one to about 3 ; R30, R31 or R32 are independently -H, an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group or a non-aromatic heterocyclic group,- or
R31 and R32, taken together with the nitrogen atom to which they are bonded, form a non-aromatic heterocyclic ring.
60. The compound of Claim 58 wherein R40 is -0-CH3.
61. The compound of Claim 60 wherein R1 is -OH.
62. The compound of Claim 60 wherein M is >C(0H)R2 and n is three .
63. The compound of Claim 62 wherein Xx is -CH2-0-, -CH2-CH2- or -CH2-S-.
64. The compound of Claim 63 wherein R2 is a substituted or unsubstituted aromatic group.
65. The compound of Claim 64 wherein R2 is an aromatic group substituted with a halogen.
66 . The compound of Claim 65 wherein R2 is a 4-chlorophenyl group .
67. A compound represented by the following structural formula:
-Y (CH2)n X N M
and physiologically acceptable salts thereof, wherein:
Y is a single covalent bond; n is an integer from one to about five;
X is a single covalent bond; and M is >NR2 or >CRXR2;
R1 is -H, -OH, an aliphatic group, -O- (aliphatic group) , -0- (substituted aliphatic group) , -SH, -S- (aliphatic group) , -S- (substituted aliphatic group) , -OC(O) - (aliphatic group), -O-C (O) - (substituted aliphatic group), -CN, -COOH, -CO-NR3R4 or -NR3R4; and
R2 is -H, -OH, an acyl group, a substituted acyl group, -NR5R6, an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group, a benzyl group, a substituted benzyl
group, a non-aromatic heterocyclic group or a substituted non-aromatic heterocyclic group; wherein:
R3, R4, R5 and R6 are independently -H, an acyl group, a substituted acyl group, an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group, a benzyl group, a substituted benzyl group, a non-aromatic heterocyclic group or a substituted non-aromatic heterocyclic group; or R1 and R2, R3 and R4 , or R5 and R6 taken together with the atom to which they are bonded, form a substituted or unsubstituted non-aromatic carbocyclic or heterocyclic ring;
Z is represented by a structural formula selected from:
wherein:
Ring C is a substituted or unsubstituted non- aromatic carbocyclic ring or a substituted or unsubstituted non-aromatic heterocyclic ring;
Ring B is a substituted or unsubstituted carbocyclic aromatic or heteroaryl group;
X-L is a covalent bond, -S-, -CH2-, -CH2-CH2-, -CH2-S-, -S-CH2-, -0-CH2-, -CHj-O-, -NRC-CH2-, -CH2-NRC-, -SO-CH2-, -CH2-SO-, -S(0)2-CH2-, -CH2-S(0)2-, -CH=CH-, -Nrc-CO- or -CO-NRc- ; wherein:
Rc is hydrogen, an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group, a benzyl group or a substituted benzyl group ; and
W is -H, -CH2-NRι:ιR12, -C^-OR1, -CH2-NH-CO-NRuR12, -CH^O-CO-NR^R12 , -CH2-NHC(0) -O-R11 or an electron withdrawing group;
R11 and R12 are independently -H, an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group or a non-aromatic heterocyclic group; or
R11 and R12, taken together with the nitrogen atom to which they are bonded, form a non-aromatic heterocyclic ring.
68. The compound of Claim 67 wherein Ring B is substituted with -OH, a halogen, -O- (aliphatic group) , -O- (substituted aliphatic group) , -0- (aromatic group) , -0- (substituted aromatic group) , an electron withdrawing group, - (0) u- (CH2) c-COOR20, - (0)u- (CH2)t-C(0) -NR21R22 or - (0) u- (CH2) t-NHC (0) -O-R20; wherein: u is zero or one; t is an integer from zero to about 3;
R20, R21 or R22 are independently -H, an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group or a non-aromatic heterocyclic group; or R21 and R22, taken together with the nitrogen atom to which they are bonded, form a non-aromatic heterocyclic ring.
69. The compound of Claim 67 wherein Rc is - (CH2) s-COOR30, - (CH2)β-C(0) -NR31R32 or - (CH2) S-NHC (0) -O-R30 ; wherein: s is an integer from zero to about 3 ;
R30, R31 or R32 are independently -H, an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group or a non-aromatic heterocyclic group; or R31 and R32, taken together with the nitrogen atom to which they are bonded, form a non-aromatic heterocyclic ring.
70. The Compound of Claim 67 wherein R1 is -OH.
71. The compound of Claim 67 wherein M is >C(OH)R2 and n is three.
72. The compound of Claim 71 R2 is a substituted or unsubstituted aromatic group.
73. A method of antagonizing a chemokine receptor in a mammal in need thereof comprising administering a compound of Claim 67.