Methods and compositions for the treatment of pain, inflammation and cancer

1 . A potent Δ5-desaturase inhibitor of formula I:

or a pharmaceutically acceptable salt or solvate thereof, wherein:

Q 1 is CR 1 , CHR 1 , N, or NR 1 ;

Q 2 is CR 1 , CHR 1 , N, or NR 1 ;

X is S, O, C(R 4 R 5 ), or N(R 4 );

Y is C(R 4 ), C(R 4 R 5 ), N, or N(R 4 );

A is a bond, CH 2 , C(O), or SO 2 ;

each R 1 is independently OR 1A , N(R 1A ) 2 , NC(O)R 1A , hydrogen, cyano, nitro, halo, or optionally substituted alkyl, aryl, alkylaryl, arylalkyl, heterocycle, alkylheterocycle or heterocyclealkyl;

each R 1A is independently hydrogen or optionally substituted alkyl, aryl, alkylaryl, arylalkyl, heterocycle, alkylheterocycle or heterocyclealkyl;

R 2 is hydrogen or optionally substituted alkyl;

each R 3 is independently OR 3A , N(R 3A ) 2 , NC(O)R 3A , hydrogen, cyano, nitro, halo, or optionally substituted alkyl, aryl, alkylaryl, arylalkyl, heterocycle, alkylheterocycle or heterocyclealkyl;

each R 3A is independently hydrogen or optionally substituted alkyl, aryl, alkylaryl, arylalkyl, heterocycle, alkylheterocycle or heterocyclealkyl;

each R 4 is independently hydrogen or optionally substituted alkyl, aryl, alkylaryl, arylalkyl, heterocycle, alkylheterocycle or heterocyclealkyl;

each R 5 is independently hydrogen or optionally substituted alkyl, aryl, alkylaryl, arylalkyl, heterocycle, alkylheterocycle or heterocyclealkyl;

n is 1-4; and

m is 1-5.

2 - 15 . (canceled)

16 . The potent Δ5-desaturase inhibitor of claim 1 , which is of formula I(a):

17 . The potent Δ5-desaturase inhibitor of claim 1 , which is of formula I(b):

18 . The potent Δ5-desaturase inhibitor of claim 1 , which is of formula I(c):

19 . The potent Δ5-desaturase inhibitor of claim 1 , which is of formula I(d):

20 . The potent Δ5-desaturase inhibitor of claim 1 , which is of formula I(e):

21 - 24 . (canceled)

25 . The potent Δ5-desaturase inhibitor of claim 1 , wherein both Q 1 and Q 2 are CR 1 .

26 . (canceled)

27 . (canceled)

28 . The potent Δ5-desaturase inhibitor of claim 1 , wherein X is N(R 4 ).

29 - 31 . (canceled)

32 . The potent Δ5-desaturase inhibitor of claim 1 , wherein Y is N or N(R 4 ).

33 - 35 . (canceled)

36 . The potent Δ5-desaturase inhibitor of claim 1 , wherein A is a bond.

37 . (canceled)

38 . (canceled)

39 . The potent Δ5-desaturase inhibitor of claim 1 , wherein R 1 is not hydrogen.

40 . The potent Δ5-desaturase inhibitor of claim 1 , wherein R 1 is halo or optionally substituted lower alkyl, aryl, or heteroaryl.

41 . (canceled)

42 . The potent Δ5-desaturase inhibitor of claim 1 , wherein R 1 is OR 1A .

43 . The potent Δ5-desaturase inhibitor of claim 42 , wherein R 1A is lower alkyl.

44 . The potent Δ5-desaturase inhibitor of claim 1 , wherein n is 1 or 2.

45 . The potent Δ5-desaturase inhibitor of claim 44 , wherein n is 1.

46 . The potent Δ5-desaturase inhibitor of claim 1 , wherein R 2 is hydrogen.

47 . The potent Δ5-desaturase inhibitor of claim 1 , wherein R 2 is lower alkyl.

48 . The potent Δ5-desaturase inhibitor of claim 1 , wherein R 3 is halo or optionally substituted lower alkyl, aryl, or heteroaryl.

49 . The potent Δ5-desaturase inhibitor of claim 48 , wherein R 3 is optionally substituted lower alkyl.

50 . The potent Δ5-desaturase inhibitor of claim 49 , wherein R 3 is halo.

51 . The potent Δ5-desaturase inhibitor of claim 1 , wherein R 3 is OR 3A .

52 . The potent Δ5-desaturase inhibitor of claim 51 , wherein R 3A is lower alkyl.

53 - 99 . (canceled)

100 . A compound of formula I(h):

or a pharmaceutically acceptable salt or solvate thereof, wherein:

R 1 is OR 1A , N(R 1A ) 2 , NC(O)R 1A , cyano, nitro, halo, or optionally substituted alkyl, aryl, or heteroaryl;

each R 1A is independently hydrogen or optionally substituted alkyl, aryl, or heteroaryl;

each R 3 is independently OR 3A , N(R 3A ) 2 , NC(O)R 3A , hydrogen, cyano, nitro, halo, or optionally substituted alkyl, aryl, alkylaryl, arylalkyl, heterocycle, alkylheterocycle or heterocyclealkyl;

each R 3A is independently hydrogen or optionally substituted alkyl, aryl, alkylaryl, arylalkyl, heterocycle, alkylheterocycle or heterocyclealkyl;

R 4 is hydrogen or optionally substituted alkyl, aryl, or heteroaryl; and

m is 1-4;

with the proviso that: 1) if R 1 is NH 2 or nitro, each R 3 is fluoro, and m is 1 or 2, then R 4 is not hydrogen; 2) if R 1 is methyl or chloro, R 3 is methyl or hydrogen, and m is 1, then R 4 is not hydrogen; 3) if R 1 is methyl, R 3 is para-chloro, and m is 1, then R 4 is not hydrogen; 4) if R 1 is halo, and each R 3 is hydrogen, then R 4 is not hydrogen; 5) if R 1 is NC(O)R 1A , then R 4 is not hydrogen; and 6) if R 1 is nitro, R 3 is cyano, and m is 1, then R 4 is not hydrogen.

101 - 122 . (canceled)

123 . A method of treating, preventing or managing pain, which comprises administering to a patient in need thereof a therapeutically or prophylactically effective amount of a potent Δ5-desaturase inhibitor of formula I:

or a pharmaceutically acceptable salt or solvate thereof, wherein:

Q 1 is C or N;

Q 2 is C or N;

X is C(R 4 R 5 ) or N(R 4 );

Y is C(R 4 ), C(R 4 R 5 ), N, or N(R 4 );

A is nothing, CH 2 , C(O), or SO 2 ;

each R 1 is independently OR 1A , N(R 1A ) 2 , NC(O)R 1A , hydrogen, cyano, nitro, halo, or optionally substituted alkyl, aryl, alkylaryl, arylalkyl, heterocycle, alkylheterocycle or heterocyclealkyl;

each R 1A is independently hydrogen or optionally substituted alkyl, aryl, alkylaryl, arylalkyl, heterocycle, alkylheterocycle or heterocyclealkyl;

R 2 is hydrogen or optionally substituted alkyl;

each R 3 is independently OR 3A , N(R 3A ) 2 , NC(O)R 3A , hydrogen, cyano, nitro, halo, or optionally substituted alkyl, aryl, alkylaryl, arylalkyl, heterocycle, alkylheterocycle or heterocyclealkyl;

each R 3A is independently hydrogen or optionally substituted alkyl, aryl, alkylaryl, arylalkyl, heterocycle, alkylheterocycle or heterocyclealkyl;

each R 4 is independently hydrogen or optionally substituted alkyl, aryl, alkylaryl, arylalkyl, heterocycle, alkylheterocycle or heterocyclealkyl;

each R 5 is independently hydrogen or optionally substituted alkyl, aryl, alkylaryl, arylalkyl, heterocycle, alkylheterocycle or heterocyclealkyl;

n is 1-4 if Q 1 and Q 2 are both C, 1-3 if one of Q 1 and Q 2 are N, or 1-2 if both Q 1 and Q 2 are N; and

m is 1-4.

124 - 127 . (canceled)

128 . A method of treating, preventing or managing inflammation, which comprises administering to a patient in need thereof a therapeutically or prophylactically effective amount of a potent Δ5-desaturase inhibitor of formula I:

or a pharmaceutically acceptable salt or solvate thereof, wherein:

Q 1 is C or N;

Q 2 is C or N;

X is C(R 4 R 5 ) or N(R 4 );

Y is C(R 4 ), C(R 4 R 5 ), N, or N(R 4 );

A is nothing, CH 2 , C(O), or SO 2 ;

each R 1 is independently OR 1A , N(R 1A ) 2 , NC(O)R 1A , hydrogen, cyano, nitro, halo, or optionally substituted alkyl, aryl, alkylaryl, arylalkyl, heterocycle, alkylheterocycle or heterocyclealkyl;

each R 1A is independently hydrogen or optionally substituted alkyl, aryl, alkylaryl, arylalkyl, heterocycle, alkylheterocycle or heterocyclealkyl;

R 2 is hydrogen or optionally substituted alkyl;

each R 3 is independently OR 3A , N(R 3A ) 2 , NC(O)R 3A , hydrogen, cyano, nitro, halo, or optionally substituted alkyl, aryl, alkylaryl, arylalkyl, heterocycle, alkylheterocycle or heterocyclealkyl;

each R 3A is independently hydrogen or optionally substituted alkyl, aryl, alkylaryl, arylalkyl, heterocycle, alkylheterocycle or heterocyclealkyl;

each R 4 is independently hydrogen or optionally substituted alkyl, aryl, alkylaryl, arylalkyl, heterocycle, alkylheterocycle or heterocyclealkyl;

each R 5 is independently hydrogen or optionally substituted alkyl, aryl, alkylaryl, arylalkyl, heterocycle, alkylheterocycle or heterocyclealkyl;

n is 1-4 if Q 1 and Q 2 are both C, 1-3 if one of Q 1 and Q 2 are N, or 1-2 if both Q 1 and Q 2 are N; and

m is 1-4.

129 - 139 . (canceled)