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US 6,784,195 B2Granted
Pyrazole compositions useful as inhibitors of ERK
AssigneeVertex Pharmaceuticals Incorporated
InventorsMichael Hale, James Janetka, Francois Maltais, Jingrong Cao
Life of this patent
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Abstract
Described herein are compounds that are useful as protein kinase inhibitors having the formula: where R1, R2, T and Ht are described in the specification. The compounds are useful for treating disease states in mammals that are alleviated by a protein kinase inhibitor, particularly diseases such as cancer, inflammatory disorders, restenosis, and cardiovascular disease.
Claims21
A compound of formula I:
- or a pharmaceutically acceptable salt thereof, wherein:
- Ht is a heterocyclic ring selected from [1,2,4]triazol-3-yl, [1,2,3]triazol-4-yl, said [1,2,4]triazol-3-yl or [1,2,3]triazol-4-yl substituted by either R3 or QR4;
- R1 is selected from R, F, Cl, N(R8)2, OR, NRCOR, NRCON(R8)2, CON(R8)2, SO2R, NRSO2R, or SO2N(R8)2;
- T is a valence bond;
- each R is independently selected from hydrogen or an optionally substituted aliphatic group having one to six carbons;
- R2 is an optionally substituted phenyl or naphthyl ring;
- R3 is selected from R, OH, OR, N(R8)2, F, Cl, or CN;
- Q is a valence bond, J, or an optionally substituted C1-6 alkylidene chain wherein up to two nonadjacent carbons of the alkylidene chain are each optionally and independently replaced by J;
- J is selected from —C(═O)—, —CO2—, —C(O)C(O)—, —NRCONR8—, —N(R)N(R8)—, —C(═O)NR8—, —NRC(═O)—, —O—, —S—, —SO—, —SO2—, —N(R)O—, —ON(R8)—, —OC(═O)N(R8)—, —N(R)COO—, —SO2N(R8)—, —N(R)SO2—, or —N(R8)—;
- R4 is selected from —R8, —R5, —NH2, —NHR5, —N(R5)2, or —NR5(CH2)yN(R5)2;
- each R5 is independently selected from R6, R7, —(CH2)yCH(R6)(R7), —(CH2)yR6, —(CH2)yCH(R6)2, —(CH2)yCH(R7)2, or —(CH2)yR7;
- y is 0-6;
- each R6 is an optionally substituted group independently selected from an aliphatic, aryl, aralkyl, aralkoxy, heteroaryl, heteroarylalkyl, heteroarylalkoxy, heterocyclyl, heterocyclylalkyl, or heterocyclylalkoxy, group;
- each R7 is independently selected from an optionally substituted aliphatic, hydroxyalkyl, alkoxyalkyl, aryloxyalkyl, or alkoxycarbonyl;
- each R8 is independently selected from R or two R8 on the same nitrogen taken together with the nitrogen optionally form a four to eight membered, saturated or unsaturated heterocyclic ring having one to three heteroatoms;
- and each substitutable ring nitrogen is independently substituted by R, NR2, COR, CO2(C1-C6 optionally substituted alkyl), SO2(C1-C6 optionally substituted alkyl), CONR2, or SO2NR2;
- provided that:
- (a) TR2 and QR4 are not the same;
- and (b) TR2 and R3 are not the same.
16 more elements
Dependencies are inferred from the claim text.