Heterocyclic amides and sulfonamides
First Claim
1. A compound of Formula I or a pharmaceutically acceptable salt or prodrug thereof, wherein R1 is C1-10 alkyl, or a C3-12 cyclic hydrocarbyl and which may contain 0, 1, 2, or 3 heteroatoms and which may be optionally substituted by 1-4 groups selected from halo, R3, C1-6 optionally substituted alkenyl, amidine, guanidine, R3CO, COOR3, CONR32, OR3, NR3R3, SR3, SO2R3NHCOR3, CN, and NHCONR32, wherein R3 is H, C1-6 alkyl or aryl each of which is optionally substituted with R, OR halo, NR2, SR, SO2R, CN, COOR, CONR2 or CF3, where each R is independently H or C1-C6 alkyl;
- L is CO or SO2;
each X is independently O, CO, CR2, or NR, where R is lower alkyl and two R groups can be joined to form a 5-7 membered ring, provided that where X is NR or O it is not directly linked to another N or O, and that not more than two X groups are CO;
n=0, 1, 2, or 3;
R2 is H, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 heteroalkyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, or heteroarylalkyl, each of which is optionally substituted with up to four groups selected from R, halo, CN, OR, ═
O, C(NR)NR2, NR2, COR, COOR, CONR2, SR, SOR, SO2R, SO2NR2, NRCOOR, and COCOOR, wherein each R is independently H, alkyl, heteroalkyl, arylalkyl, or diarylalkyl, each of which may be substituted with hydroxy, amino, C1-C6 alkoxy, C1-C6-alkyl-COOR, C1-C6-alkyl-CONR2 or halo, and wherein two R groups can cyclize to form a 3 to 8 membered ring, optionally including up to two heteroatoms selected from N, O and S;
Y is NR4R5 or OR5, wherein R4 is H or C1-6 alkyl which is optionally substituted with R, OR, NR2, SR, SO2R, halo, COOR, ═
O, NRCOOR, COR, NRCOR, aryl, arylalkyl, arylalkoxy, or CONR2, wherein each R is independently H or C1-C6 alkyl;
each R5 is independently H, a C1-10 alkyl optionally substituted with a hydrocarbyl or heterocyclic ring or ring system which may contain 0, 1, 2, or 3 heteroatoms selected from O, N and S, and which is optionally substituted with R, OR, NR2, SR, SO2R, halo, COOR, ═
O, NRCOOR, COR, NRCOR, aryl, arylalkyl, arylalkoxy, or CONR2, wherein each R is independently H or C1-C6 alkyl;
or a C3-7 cycloalkyl, aryl, arylalkyl, heteroaryl, or a fused or unfused carbocyclic or heterocyclic ring, each of which is optionally substituted with up to four groups selected from R, OR, NR2, SR, SO2R, halo, COOR, ═
O, and CONR2, wherein each R is independently H or C1-C6 alkyl; and
one of Z1 and Z2 is CH, and the other is either CH or N.
1 Assignment
0 Petitions
Accused Products
Abstract
The invention is directed to compounds and methods to inhibit p38 kinase wherein the compounds are a pyrimidine or pyridine coupled to two mandatory substituents.
15 Citations
36 Claims
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1. A compound of Formula I
or a pharmaceutically acceptable salt or prodrug thereof, wherein R1 is C1-10 alkyl, or a C3-12 cyclic hydrocarbyl and which may contain 0, 1, 2, or 3 heteroatoms and which may be optionally substituted by 1-4 groups selected from halo, R3, C1-6 optionally substituted alkenyl, amidine, guanidine, R3CO, COOR3, CONR32, OR3, NR3R3, SR3, SO2R3NHCOR3, CN, and NHCONR32, wherein R3 is H, C1-6 alkyl or aryl each of which is optionally substituted with R, OR halo, NR2, SR, SO2R, CN, COOR, CONR2 or CF3, where each R is independently H or C1-C6 alkyl; -
L is CO or SO2;
each X is independently O, CO, CR2, or NR, where R is lower alkyl and two R groups can be joined to form a 5-7 membered ring, provided that where X is NR or O it is not directly linked to another N or O, and that not more than two X groups are CO;
n=0, 1, 2, or 3;
R2 is H, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 heteroalkyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, or heteroarylalkyl, each of which is optionally substituted with up to four groups selected from R, halo, CN, OR, ═
O, C(NR)NR2, NR2, COR, COOR, CONR2, SR, SOR, SO2R, SO2NR2, NRCOOR, and COCOOR, wherein each R is independently H, alkyl, heteroalkyl, arylalkyl, or diarylalkyl, each of which may be substituted with hydroxy, amino, C1-C6 alkoxy, C1-C6-alkyl-COOR, C1-C6-alkyl-CONR2 or halo, and wherein two R groups can cyclize to form a 3 to 8 membered ring, optionally including up to two heteroatoms selected from N, O and S;
Y is NR4R5 or OR5, wherein R4 is H or C1-6 alkyl which is optionally substituted with R, OR, NR2, SR, SO2R, halo, COOR, ═
O, NRCOOR, COR, NRCOR, aryl, arylalkyl, arylalkoxy, or CONR2, wherein each R is independently H or C1-C6 alkyl;
each R5 is independently H, a C1-10 alkyl optionally substituted with a hydrocarbyl or heterocyclic ring or ring system which may contain 0, 1, 2, or 3 heteroatoms selected from O, N and S, and which is optionally substituted with R, OR, NR2, SR, SO2R, halo, COOR, ═
O, NRCOOR, COR, NRCOR, aryl, arylalkyl, arylalkoxy, or CONR2, wherein each R is independently H or C1-C6 alkyl;
or a C3-7 cycloalkyl, aryl, arylalkyl, heteroaryl, or a fused or unfused carbocyclic or heterocyclic ring, each of which is optionally substituted with up to four groups selected from R, OR, NR2, SR, SO2R, halo, COOR, ═
O, and CONR2, wherein each R is independently H or C1-C6 alkyl; and
one of Z1 and Z2 is CH, and the other is either CH or N. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36)
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Specification