Aminotriazole compounds useful as inhibitors of protein kinases

1. A compound having the formula II:

or a pharmaceutically acceptable salt thereof, wherein

R 1 is hydrogen or C 1-6 alkyl;

R 2 is Ar 1 or Cy 1 , wherein Ar 1 is an aryl group selected from phenyl, pyrrolyl, pyrazolyl, triazolyl, imidazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl, or thiadiazolyl and Cy 1 is selected from pyrrolidinyl, pyrazolinyl, thiazolidinyl, or imidazolidinyl; wherein each of Ar 1 and Cy 1 is optionally substituted with 0–5 independent occurrences of Q-R X ; wherein each independent occurrence of Q is a bond or is a C 1-6 alkylidene chain wherein up to two non-adjacent methylene units of Q are optionally replaced by CO, CO 2 , COCO, CONR, OCONR, NRNR, NRNRCO, NRCO, NRCO 2 , NRCONR, SO, SO 2 , NRSO 2 , SO 2 NR, NRSO 2 NR, O, S, or NR; and each independent occurrence of R X is independently selected from R′, halogen, NO 2 , CN, OR′, SR′, N(R′) 2 , NR′C(O)R′, NR′C(O)N(R′) 2 , NR′CO 2 R′, C(O)R′, CO 2 R′, OC(O)R′, C(O)N(R′) 2 , OC(O)N(R′) 2 , SOR′, SO 2 R′, SO 2 N(R′) 2 , NR′SO 2 R′, NR′SO 2 N(R′) 2 , C(O)C(O)R′, or C(O)CH 2 C(O)R′;

R 3 is Ar 2 or Cy 2 , wherein Ar 2 is an unsubstituted aryl group selected from phenyl, pyrrolyl, pyrazolyl, triazolyl, imidazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl, or thiadiazolyl and Cy 2 is a group selected from pyrrolidinyl, pyrazolinyl, thiazolidinyl, or imidazolidinyl, optionally substituted with up to five substituents selected from Z-R Y ; wherein Z is a bond or is a C 1-6 alkylidene chain wherein up to two non-adjacent methylene units of Z are optionally replaced by CO, CO 2 , COCO, CONR, OCONR, NRNR, NRNRCO, NRCO, NRCO 2 , NRCONR, SO, SO 2 , NRSO 2 , SO 2 NR, NRSO 2 NR, O, S, or NR; and each occurrence of R Y is independently selected from R′, halogen, NO 2 , CN, OR′, SR′, N(R′) 2 , NR′C(O)R′, NR′C(O)N(R′) 2 , NR′CO 2 R′, C(O)R′, CO 2 R′, OC(O)R′, C(O)N(R′) 2 , OC(O)N(R′) 2 , SOR′, SO 2 R′, SO 2 N(R′) 2 , NR′SO 2 R′, NR′SO 2 N(R′) 2 , C(O)C(O)R′, or C(O)CH 2 C(O)R′; and

each occurrence of R is independently selected from hydrogen or an optionally substituted C 1-6 aliphatic group; and each occurrence of R′ is independently selected from hydrogen or an optionally substituted group selected from C 1-8 aliphatic, C 1-10 aryl, a heteroaxyl ring having 5–10 ring atoms, or a heterocyclyl ring having 3–10 ring atoms, or wherein R and R′ taken together, or two occurrences of R′ taken together, form a 5–8 membered cycloalkyl, heterocyclyl, aryl, or heteroaryl ring having 0–3 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

provided that

when R 3 is unsubstituted phenyl and R 1 is hydrogen, then R 2 is not unsubstituted phenyl.

2. The compound of claim 1 , wherein R 1 is hydrogen; R 2 is optionally substituted phenyl; R 3 is Ar 2 or Cy 2 ; and said compound has formula II-A-(ii) or II-A-(iii):

wherein x is 0–5, n is 0, and m is 0.

3. The compound of any one of claims 1 – 2 wherein R 3 is -(L) m Ar 2 and Ar 2 is selected from one of the following groups:

wherein ZR y is hydrogen.

4. The compound of claim 1 , wherein R 1 is hydrogen; R 2 is Ar 1 or Cy 1 ; and R 3 is Ar 2 , wherein Ar 2 is phenyl or thiazolyl.

5. A compound selected from one of the following compounds:

6. The compound:

7. A composition comprising a compound according to any one of claims 1 – 2 , 4 , or 5 – 6 and pharmaceutically acceptable carrier, adjuvant, or vehicle.

8. The composition of claim 7 , further comprising an additional therapeutic agent selected from a chemotherapeutic or an anti-proliferative agent.