PATENTSCOPE will be unavailable a few hours for maintenance reason on Tuesday 19.11.2019 at 4:00 PM CET
Search International and National Patent Collections
Some content of this application is unavailable at the moment.
If this situation persists, please contact us atFeedback&Contact
1. (WO2007005403) 5,6-DI-SUBSTITUTED OXADIAZOLOPYRAZINES AND THIADIAZOLOPYRAZINES AS CXC-CHEMOKINE RECEPTOR LIGANDS
Note: Text based on automatic Optical Character Recognition processes. Please use the PDF version for legal matters

WHAT IS CLAIMED IS:

1. A compound of the formula:


and the pharmaceutically acceptable salts thereof, wherein: X is O or S;
A is selected from the group consisting of:




A44
A is a group selected from the group consisting of A1 , A2, A3, A4, A5, A6, A7, A8, A9, A10, A13, A14, A15, A16, A17, A18, A19, A20, A21 , A22, A23, A24, A25, A26, A27, A28, A29, A30, A31 , A32, A33, A34, A35, A36 and A37 (as defined above) wherein said A group is substituted with 1 to 6 independently selected R9 groups; or A is a group selected from the group consisting of: A11 and A12 (as defined above) wherein said A group is substituted with 1 to 3 independently selected R9 groups;
B is selected from the group consisting of:



B15 B16 B17 B18
n is 0 to 6;
p is 1 to 5;
X1 is O, NH, or S;
Z is 1 to 3;
R2 is selected from the group consisting of: hydrogen, OH, -C(O)OH1 -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, -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;
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)NR13OR14, 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 (e.g., 1 to 6) substituents on said substituted R7 and R8 groups, wherein each substituent 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, I) -CO2R13, m) -C(O)NR13R14, n) -SO2NR13R14, o) -SO2R13, p) -OC(O)R13, q) -OC(O)NR13R14, r) -NR13C(O)R14 , and
s) -NR13CO2R14;
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) -OR13, f) -NR13R14, g) -NO2, h) -CN1 i) -SO2R13, j) -SO2NR13R14, k) -NR13COR14, 1) -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, hydrogen, alkyl, halogen, -CF3, -OCF3, -NR13R14, -NR13C(O)NR13R14, -OH, -C(O)OR13, -SH, -SOrøNR13R14, -SO2TR137l^HC(O)Rt3r-NH"Sl)7NR13R14r-NHS02R13,
-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 aryl, unsubstituted or substituted heteroaryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heteroarylalkyl, unsubstituted or substituted cycloalkyl, 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, -SO2R15 provided that R15 is not H, 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 (preferably a 3 to 7 membered 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: alkyl, aryl, hydroxy, hydroxyalkyl, alkoxy, alkoxyalkyl, arylalkyl, fluoroalkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, amino, -C(O)OR15, -C(O)NR15R16,
-SO1NR15R16, -C(O)R15, -SO2R15 provided that R15 is not H, -NHC(O)NR15R16,
-NHC(O)OR15, halogen, and a heterocylcoalkenyl group;
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 O1 1 or 2.

2. The compound of Claim 1 wherein X is O.
3. The compound of Claim 1 wherein X is S.
4. The compound of Claim 1 wherein B is selected from the group consisting of B1 to B7, and wherein for B1 the substitutent R3 is selected from the group consisting of: -C(O)NR13R14,



5. The compound of Claim 1 wherein B is B1 and R3 for B1 is selected from the group consisting of:-C(O)NR13R14,



6. The compound of Claim 1 wherein B is B1 of the formula B1.1 :



B1 .1
7. The compound of Claim 6 wherein for B1.1 R2 for B1.1 is -OH, and R13 and R14 for B1.1 are each the same or different alkyl group.
8. The compound of Claim 1 wherein B is B1 and R3 for B1 is selected from the group consisting of:



9. The compound of Claim 6 wherein R2 for B1.1 is -OH.
10. The compound of Claim 6 wherein R13 and R14 for B1.1 are each the same or different alkyl group.

11. The compound of Claim 1 wherein B is B1 of the formula B1.2:



B1.2
12. The compound of Claim 11 wherein R2 for B1.2 is -OH.
13. The compound of Claim 11 wherein R13 and R14 for B1.2 are the same or different alkyl group.
14. The compound of Claim 13 wherein the R2 substituent for B1.2 is -OH.

15. The compound of Claim 13 wherein R13 and R14 for B1.2 are methyl.
16. The compound of Claim 15 wherein the R2 substituent for B1.2 is -OH.

17. The compound of Claim 1 wherein B is selected from the group consisting of groups B2, B3, B4, B5 and B6.
18. The compound of Claim 1 wherein B is B3.
19. The compound of Claim 18 wherein R11 for B3 is H.
20. The compound of Claim 18 wherein R2 for B3 is -OH.
21. The compound of Claim 18 wherein R3 for B3 is -C(O)NR13R14.
22. The compound of Claim 18 wherein R2 for B3 is -OH and R3 for B3 is

-C(O)NR13R14.
23. The compound of Claim 18 wherein R2 for B3 is -OH, R3 for B3 is -C(O)NR13R14, and R11 for B3 is H.
24. The compound of Claim 23 wherein R13 and R14 for B3 are each independently selected from the group consisting of: alkyl, unsubstituted heteroaryl and substituted heteroaryl.
25. The compound of Claim 18 wherein R3 for B3 is -S(O)1NR13R14.
26. The compound of Claim 25 wherein R2 for B3 is -OH.
27. The compound of Claim 26 wherein the R13 and R14 substituents for B3 are the same or different and are selected from the group consisting of: H and alkyl.

28. The compound of Claim 27 wherein each R13 and R14 for B3 are independently selected from the group consisting of: H, methyl, ethyl, isopropyl and t-butyl.
29. The compound of Claim 28 wherein R13 and R14 are ethyl.
30. The compound of Claim 1 wherein B is B7.

31. The compound of Claim 1 wherein B is B8.
32. The compound of Claim 1 wherein A is selected from the group consisting of: A1 , A2, A3, A4, A5, A6, A8, A9, A11, A14, A15, A16, A20, A41 , A42 and A45, wherein:
said A1 , A2, A3, A4, A5, A6, A8, A9, A11 , A14, A15, A16, A20 groups are unsubstituted, or are substituted with 1 to 3 substituents independently selected from the group consisting of: halogen, alkyl, cycloalkyl, -CF3, cyano, -OCH3, and -NO2, each R7 and R8 for said A1 , A2, A3, A4, A5, A6, A8, A9, A11 , A14, A15, A16, A20 groups is independently selected from the group consisting of: H, alkyl, fluoroalkyl, cycloalkyl, and cycloalkylalkyl, and R9 for said A1 , A2, A3, A4, A5, A6, A8, A9, A11 , A14, A15, A16, A20 groups is selected from the group consisting of: H, halogen, alkyl, cycloalkyl, -CF3, cyano, -OCH3, and -NO2, and
said R7 and R8 substituents for said A41 , A42 and A45 groups are each independently selected from the group consisting of: H, alkyl, fluoroalkyl, cycloalkyl, and cycloalkylalkyl; wherein R8a is as defined in formula 1.0, and R9 for said A41 , A42 and A45 groups is selected from the group consisting of: H, halogen, alkyl, cycloalkyl, -CF3, cyano, -OCH3, and -NO2.
33. The compound of Claim 1 wherein A is selected from the group consisting of: A8, A11 , A15, A16, and A37, and all other substitutents are as defined for formula 1.0.
34. The compound of Claim 1 wherein A is A8 wherein the furan ring is unsubstituted or substituted.
35. The compound of Claim 1 wherein A is is A8 wherein the furan ring is substituted.
36. The compound of Claim 1 wherein A is A8 wherein the furan ring is substituted with at least one alkyl group.
37. The compound of Claim 34 wherein R7 and R8 are independently selected from the group consisting of: H and alkyl.
38. The compound of Claim 37 wherein R7 is H, and R8 is alkyl.
39. The compound of Claim 36 wherein R7 and R8 are independently selected from the group consisting of: H and alkyl.
40. The compound of Claim 39 wherein R7 is H, and R8 is alkyl.

41. The compound of Claim 1 wherein A is selected from the group consisting of:


A8.20




42. The compound of Claim 6 wherein A is A8 wherein the furan ring of said A8 is unsubstituted, or wherein the furan ring of said A8 is substituted with at least one alkyl group, and wherein R7 and R8 are independently selected from the group consisting of: H and alkyl.
43. The compound of Claim 7 wherein A is A8 wherein the furan ring of said A8 is unsubstituted, or wherein the furan ring of said A8 is substituted with at least one alkyl group, and wherein R7 is H and R8 is alkyl.
44. The compound of Claim 11 wherein A is A8 wherein the furan ring of said A8 is unsubstituted, or wherein the furan ring of said A8 is substituted with at least one alkyl group, and wherein R7 is H and R8 is alkyl.
45. The compound of Claim 12 wherein A is A8 wherein the furan ring of said A8 is unsubstituted, or wherein the furan ring of said A8 is substituted with at least one alkyl group, and wherein R7 is H and R8 is alkyl.
46. The compound of Claim 14 wherein A is A8 wherein the furan ring of said A8 is unsubstituted, or wherein the furan ring of said A8 is substituted with at least one alkyl group, and wherein R7 is H and R8 is alkyl.
47. The compound of Claim 1 wherein B is B3.

48. The compound of Claim 47 wherein R2 for B3 is -OH, R3 for B3 is selected from the group consisting of: -SO2NR13R14 and -CONR13R14, R11 for B3 is H, and each R13 and R14 for B3 are independently selected from the group consisting of: H, methyl, ethyl, isopropyl and t-butyl.
49. The compound of Claim 48 wherein R3 for B3 is -SO2NR13R14.
50. The compound of Claim 1 wherein
substitutent A is selected from the group consisting of: A1 , A2, A3, A4, A5, A6, A8, A9, A11 , A14, A15, A16, A20, A41 , A42 and A45, and wherein said groups A1 , A2, A3, A4, A5, A6, A8, A9, A11 , A14, A15, A16 and A20 are unsubstitued or substituted, and each R7 and R8 for said A groups 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, fluoroalkyl, alkynyl, alkenyl, and cycloalkenyl, and wherein said substituents on said R7 and R8 substituted groups are selected from the group consisting of: a) cyano, b) -CO2R13,
c) -C(O)NR13R14, d) -SO2NR13R14, e) -NO2, f) -CF3, g) -OR13, h) -NR13R14,
I) -^JC(O)R13, j) -OC(O)NR13R14, and k) halogen, and R8a and R9 for said A groups are as defined in formula 1.0, and
substituent B is B3 wherein:
R2 for B3 is selected from the group consisting of: H, OH, -NHC(O)R13 and -NHSO2R13,
R3 for B3 is selected from the group consisting of: -SO2NR13R14, -NO2, cyano, -C(O)NR13R14, -SO2R13, and -C(O)OR13,
R11 for B3 is selected from the group consisting of: R13, hydrogen, halogen,

-CF3, -NR13R14, -NR13C(O)NR13R14, -C(O)OR13, -SH, -SO(t)NR13R14,-SO2R13,
-NHC(O)R13, -NHSO2NR13R14, -NHSO2R13, -C(O)NR13R14, -C(O)NR13OR14,
-OC(O)R13, -COR13, -OR13, and cyano,
each R13 and R14 for B3 is independently selected from the group consisting of: H, methyl, ethyl, isopropyl and t-butyl, or
R13 and R14 for B3 when 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 optionally having one additional heteroatom selected from the group consisting of: O, S or NR18; wherein R18 is selected from the group consisting of: H, alkyl, aryl, heteroaryl, -C(O)R19, -SO2R19 and -C(O)NR19R20, wherein each R19 and R20 is independently selected from the group consisting of:
alkyl, aryl and heteroaryl, wherein there are 1 to 3 substituents on the substituted

5 cyclized R13 and R14 groups 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)OR15,
-C(O)NR15R16, -SO1NR15R16, -C(O)R15, -SO2R15 provided that R15 is not H,
-NHC(O)NR15R16 and halogen, and wherein each R15 and R16 is independently lό selected from the group consisting: of H, alkyl, aryl, arylalkyl, cycloalkyl and
heteroaryl.
51. The compound of Claim 1 wherein
A is selected from the group consisting of:



15 wherein A8, A15.1 , A16.1 , A20.1 and A20.2 are unsubstituted, or A8, A15.1 , A16.1 ,
A20.1 and A20.2 are substituted with 1 to 3 substituents independently selected from the group consisting of: F, Cl, Br, alkyl, cycloalkyl, and -CF3, R7 for A8, A15.1 , A16.1 , A20.1 and A20.2 is selected from the group consisting of: H, -CF3, -CF2CH3, methyl, ethyl, isopropyl, cyclopropyl and t-butyl, and R8 for A8, A15.1 , A16.1 , A20.1 and A20.2 20 is H, and wherein R7 for A45 is selected from the group consisting of: H, -CF3,
-CF2CH3, methyl, ethyl, isopropyl, cyclopropyl and t-butyl, and R8 for A45 is H and R8a for A45 is as defined for formula 1.0, and
(2) B is B3 wherein R2 for B3 is selected from the group consisting of: H, OH, -NHC(O)R13 and -NHSO2R13, R3 for B3 is -SO2NR13R14, R11 for B3 is selected 25 from the group consisting of: H, halogen and alkyl, and each R13 and R14 for B3 is
independently selected from the group consisting of: H, methyl, ethyl, isopropyl, and t-butyl.
52. The compound of Claim 1 wherein said compound is a calcium salt.
53. The compound of Claim 1 wherein said compound is a sodium salt.

54. The compound of Claim 1 selected from the group consisting of the final compounds of Examples 1 , 2a, 2b, 3a, 3b, 4a, 4b, 5a, 5b, 6a, 6b, 7a, 7b, 8a, 8b, 9a, 9b, 10a, 10b, 11 a, 11 b, 12a, 12b, 13a, 13b, 14a, 14b, 15a, 15b, 16a, 16b, 17a, 17b, 18a, 18b, 19a, 19b, 20a, 20b, 21a, 21 b, 22a, 22b, 23a, 23b, 24a, 24b, 25a, 25b, 26a, 26b, 27a, 27b, 28a, 28b, 29a, 29b, 30a, 30b, 31a, 31 b, 32a, 32b, 33a, 33b, 34a, 34b, 35a, 35b, 36a, 36b, 37a, 37b, 38a, 38b, 39a, 39b, 40a, 40b, 41a, 41 b, 42a, 42b, 43a, 43b, 44a, 44b, 45a, 46a, 46b, 47a, 47b, 48a, 48b, 49a, 49b, 50a, 50b, 51a, 51b, 52a, and 52b.
55. The compound of Claim 1 selected from the group consisting of the final compounds of Examples 2a, 2b, 3a, 3b, 5a, 5b, 7a, 7b, 8a, 8b, 9a, 9b, 10a, 10b, 14a,

14b, 15a, 15b, 16a, 16b, 17a, 17b, 18a, 18b, 19a, 19b, 21a, 21 b, 22a, 22b, 24a, 24b, 25a, 25b, 26a, 26b, 27a, 27b, 28a, 28b, 29a, 29b, 30a, 30b, 31a, 31 b, 32a, 32b, 35a, 35b, 37a, 37b, 39a, 39b, 40a, 40b, 41a, 41 b, 42a, 42b, 44a, 44b, 45a, 45b, 46a, 46b, 48a, 48b, 50a, and 50b.
56. The compound of Claim 1 selected from the group consisting of the final compounds of Examples 3a, 3b, 5a, 5b, 8a, 8b, 10a, 10b, 14a, 14b, 16a, 16b, 17a, 17b, 18a, 18b, 19a, 19b, 26a, 26b, 28a, 28b, 30a, 30b, 31a, 31b, 37a, 37b, 40a, 40b, 41a, 41 b,
45b, 46a, 46b, 48a, and 48b.
57. The compound of Claim 1 selected from the group consisting of the final compounds of Examples 3a, 3b, 5a, 5b, 8a, 8b, 10a, 10b, 14a, 14b, 17a, 17b, 18a,

18b, 22a, 22b, 28a, 28b, 29a, 29b, 32a, 32b, 40a, 40b, 41a, 41b, 45a, and 45b.
58. The compound of Claim 54 wherein said compound is a calcium or sodium salt.
59. The compound of Claim 1 in pure or isolated form.
60. A pharmaceutical composition comprising an effective amount of at least one compound of Claim 1 , or a pharmaceutically acceptable salt thereof, in
combination with a pharmaceutically acceptable carrier.
61. A pharmaceutical composition comprising an effective amount of at least one compound of Claim 54, or a pharmaceutically acceptable salt thereof, in combination with a pharmaceutically acceptable carrier.
62. The use of at least one compound of Claim 1 , or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament for treating a
chemokine-mediated disease.

63. The use of Claim 62 wherein said disease is selected from the group consisting of: pain, acute inflammatory pain, chronic inflammatory pain, acute neuropathic pain, and chronic neuropathic pain, psoriasis, atopic dermatitis, asthma, COPD, cancer, adult respiratory disease, arthritis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, septic shock, endotoxic shock, gram negative sepsis, toxic shock syndrome, stroke, cardiac and renal reperfusion injury,
glomerulonephritis, thrombosis, Alzheimer's disease, graft vs. host reaction, allograft rejections, malaria, acute respiratory distress syndrome, delayed type hypersensitivity reaction, atherosclerosis, cerebral and cardiac ischemia, osteoarthritis, multiple sclerosis, restinosis, angiogenesis, osteoporosis, gingivitis, respiratory viruses, herpes viruses, hepatitis viruses, HIV, Kaposi's sarcoma associated virus, meningitis, cystic fibrosis, pre-term labor, cough, pruritis, multi-organ dysfunction, trauma, strains, sprains, contusions, psoriatic arthritis, herpes, encephalitis, CNS vasculitis, traumatic brain injury, CNS tumors, subarachnoid hemorrhage, post surgical trauma, interstitial pneumonitis, hypersensitivity, crystal induced arthritis, acute and chronic pancreatitis, acute alcoholic hepatitis, necrotizing enterocolitis, chronic sinusitis, angiogenic ocular disease, ocular inflammation, retinopathy of prematurity, diabetic retinopathy, macular degeneration with the wet type preferred and corneal neovascularization,
polymyositis, vasculitis, acne, gastric and duodenal ulcers, celiac disease,
esophagitis, glossitis, airflow obstruction, airway hyperresponsiveness, bronchiectasis, bronchiolitis, bronchiolitis obliterans, chronic bronchitis, cor pulmonae, cough, dyspnea, emphysema, hypercapnea, hyperinflation, hypoxemia, hyperoxia-induced inflammations, hypoxia, surgical lung volume reduction, pulmonary fibrosis, pulmonary hypertension, right ventricular hypertrophy, peritonitis associated with continuous ambulatory peritoneal dialysis (CAPD), granulocytic ehrlichiosis, sarcoidosis, small airway disease, ventilation-perfusion mismatching, wheeze, colds, gout, alcoholic liver disease, lupus, burn therapy, periodontitis, transplant reperfusion injury and early transplantation rejection.
64. The use of Claim 63 wherein cancer is treated.
65. The use of Claim 63 wherein the medicament is used for treating cancer, and said medicament is used in combination with at least one anticancer agent.
66. The use of Claim 65 wherein said anticancer agent is selected from the group consisting of: alkylating agents, antimetabolites, natural products and their derivatives, hormones, anti-hormones, anti-angiogenic agents and steroids, and synthetics.
67. The use of Claim 63 wherein the medicament is used for treating cancer, said medicament being used concurrently or sequentially with a microtubule affecting agent or an antineoplastic agent or an anti-angiogenesis agent or a VEGF receptor kinase inhibitor or antibodies against the VEGF receptor or interferon, and/or radiation.
68. The use of Claim 63 wherein the medicament is used for treating cancer, said medicament being used in combination with one or more antineoplastic agents selected from the group consisting of: gemcitabine, paclitaxel, 5-Fluorouracil, cyclophosphamide, temozolomide, taxotere and Vincristine.
69. The use of Claim 63 wherein the medicament is used for treating cancer, said medicament being used concurrently or sequentially with an antineoplastic agent, microtubule affecting agent or anti-angiogenesis agent.
70. The use of Claim 69 wherein a microtubule affecting agent is used.
71. The use of Claim 70 wherein said microtubule affecting agent is paclitaxel.
72. The use of Claim 63 wherein cancer is treated, and said cancer selected from the group consisting of: melanoma, gastric carcinoma, and non-small cell lung carcinoma.
73. A use of at least one compound of Claim 1 , or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament for inhibiting
angiogenesis.
74. A use of at least one compound of Claim 1 , or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament for inhibiting
angiogenesis, said medicament being used in combination with an effective amount of at least one anti-angiogenesis compound.
75. The use of Claim 63 wherein the chemokine mediated disease is an angiogenic ocular disease.
76. The use of Claim 75 wherein said angiogenic ocular disease is selected from the group consisting of: ocular inflammation, retinopathy of prematurity, diabetic retinopathy, macular degeneration with the wet type preferred and corneal
neovascularization.

77. The use of Claim 63 wherein the disease treated is COPD.
78. The use of Claim 63 wherein the disease treated is pain.
79. The use of Claim 63 wherein the disease treated is rheumatoid arthritis.

80. The use of Claim 63 wherein the disease treated is acute inflammation, acute inflammatory pain, chronic inflammatory pain, acute neuropathic pain and chronic neuropathic pain.