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.

Abstract: The invention is directed to methods to inhibit p38 kinase, preferably p38-? using compounds which are azaindoles wherein the azaindoles are coupled through a piperidine or piperazine type linker to another cyclic moiety.

Abstract: The invention concerns methods of treating malignant gliomas, by administering inhibitors of TGF-? the TGF-? signaling pathway, including molecules preferably binding to the type I TGF-? receptor (TGF?-R1). Preferably, the inhibitors are non-peptide small molecules, including quinazoline derivatives. The invention also concerns methods for reversing the TGF-?-mediated effect on glioma cells to make them less refractile to signaling and other immune cells, comprising contacting a glioma cell or tissue in vivo or in vitro, with an inhibitor of TGF-?.

Abstract: The invention is directed to methods to inhibit TGF-? and/or p38-? kinase using compounds of the formula or the pharmaceutically acceptable salts thereof wherein R3 is a noninterfering substituent; each Z is CR2 or N, wherein no more than two Z positions in ring A are N, and wherein two adjacent Z positions in ring A cannot be N; each R2 is independently a noninterfering substituent; L is a linker; n is 0 or 1; and Ar? is the residue of a cyclic aliphatic, cyclic heteroaliphatic, aromatic or heteroaromatic moiety optionally substituted with 1-3 noninterfering substituents.

Abstract: The present invention is directed to a process for making 2-substituted pyridopyrimidones. In particular, 2-substituted pyridopyrimidones are made through the single step reaction of suitable acid derivatives with desired derivatives of amidines.

Abstract: The invention is directed to methods to inhibit TGF-? and/or p38-? kinase using compounds of the formula or the pharmaceutically acceptable salts thereof wherein R3 is a noninterfering substituent; each Z is CR2 or N, wherein no more than two Z positions in ring A are N, and wherein two adjacent Z positions in ring A cannot be N; each R2 is independently a noninterfering substituent; L is a linker; n is 0 or 1; and Ar? is the residue of a cyclic aliphatic, cyclic heteroaliphatic, aromatic or heteroaromatic moiety optionally substituted with 1-3 noninterfering substituents.

Abstract: Compounds that inhibit p38-? kinase are those wherein a bicyclic aromatic system is coupled through a saturated ring to an aryl group.

Abstract: The invention is directed to methods to inhibit p38-? kinase using compounds comprising saturated heterocycles coupled to a fused ring system.

Abstract: The invention is directed to methods to inhibit TGF-? and/or p38-? kinase using compounds of the formula or the pharmaceutically acceptable salts thereof wherein R3 is a noninterfering substituent; each Z is CR2 or N, wherein no more than two Z positions in ring A are N, and wherein two adjacent Z positions in ring A cannot be N; each R2 is independently a noninterfering substituent; L is a linker; n is 0 or 1; and Ar? is the residue of a cyclic aliphatic, cyclic heteroaliphatic, aromatic or heteroaromatic moiety optionally substituted with 1-3 noninterfering substituents.

Abstract: Compound with an indole linked through an aliphatic ring system to an aromatic moiety are useful in treating conditions associated with enhanced P38? kinase activity.

Abstract: Quinazoline derivatives have the formula: or the pharmaceutically acceptable salts thereof; wherein each of Z5, Z6, Z7 and Z8 is N or CH and wherein one or two Z5, Z6, Z7 and Z8 are N and wherein two adjacent Z positions cannot be N; wherein m and n are each independently 0-3; wherein R1 is independently OH, SH, NH2, OR, SR, NHR, halo or R-halide; wherein two adjacent R1 groups may be joined to form an aliphatic hetero cycle ring of 5-6 members; wherein R2 is independently R, halo, R-halide, OR-halide, NH2, CONH2 or CONHR; wherein R is optionally substituted C1-C12 alkyl, C1-C12 alkenyl, C1-C12 alkynyl, or aryl C1-C12 alkyl, containing 0-4 heteroatoms in place of a carbon in the carbon backbone, where the optional substituents are ?O, ?N, or OH; and wherein R3 is H or CH3. Such compounds are useful in pharmaceutical compositions and methods of treating conditions characterized by enhanced TGF? activity.

Abstract: Improved reagents and methods of amination are provided. The reagents are phenyl hydroxylamines containing one nitro and at least one CF3 substituent on the phenyl moiety.

Abstract: The invention is directed to methods to inhibit p38-? kinase using compounds of the formula and the pharmaceutically acceptable salts thereof, or a pharmaceutical composition thereof, wherein represents a single or double bond; one Z2 is CA or CR8A and the other is CR1, CR12, NR6 or N wherein each R1, R6 and R8 is independently hydrogen or noninterfering substituent; A is —Wi—COXjY wherein Y is COR2 or an isostere thereof and R2 is hydrogen or a noninterfering substituent, each of W and X is a spacer of 2-6 ?, and each of i and j is independently 0 or 1; as Z3 is NR7 or O; each R3 is independently a noninterfering substituent; n is 0-3; each of L1 and L2 is a linker; each R4 is independently a noninterfering substituent; m is 0-4; Z1 is CR5 or N wherein R5 is hydrogen or a noninterfering substituent; each of 1 and k is an integer from 0-2 wherein the sum of 1 and k is 0-3; Ar is an aryl group substituted with 0-5 noninterfering substituents, wherein two noninterfering substituents can form a fused ring

Abstract: The invention is directed to methods to inhibit p38-? kinase using compounds which contain a phenyl group linked through a piperazine ring to a substituted indole.

Abstract: Compounds in which a pyrimidine nucleus is bridged at the 5 and 6 position and are further substituted at positions 2 and 4 with substituents comprising aromatic moieties are useful in treating subjects with conditions ameliorated by inhibition of TGF? activity.

Abstract: The invention is directed to methods to inhibit p38-&agr; kinase using compounds of the formula and the pharmaceutically acceptable salts thereof, or a pharmaceutical composition thereof, wherein represents a single or double bond; B is —Wi—COXjY wherein Y is COR2 or an isostere thereof and R2 is hydrogen or a noninterfering substituent, each of W and X is a spacer of 2-6 Å, and each of i and j is independently 0 or 1; each R3 is independently a noninterfering substituent, where n is 0-3; Z3 is NR7 or O; wherein R7 is H or a noninterfering substituent; one Z2 is CA or CR8A and the other is CR1, CR12, NR6 or N wherein each R1, R6 and R8 is independently hydrogen or noninterfering substituent; wherein A is: such that Z1 is CR5 or N wherein R5 is hydrogen or a noninterfering substituent; each of l and k is an integer from 0-2 wherein the sum of l and k is 0-3; Ar is an aryl group substituted with 0-5 noninterfering substituents, wherein two noninterfe

Abstract: The invention is directed to methods to inhibit p38 kinase, preferably p38-&agr; using compounds which are azaindoles wherein the azaindoles are coupled through a piperidine or piperazine type linker to another cyclic moiety.

Abstract: The invention is directed to inhibition of p38-&agr; kinase using compounds of the formula 1

Abstract: The invention is directed to methods to inhibit p38-&agr; kinase using compounds comprising a phenyl or thienyl coupled through a piperidine or piperazine nucleus to an indole residue wherein the indole residue mandatorily has a substituent on the ring nitrogen which is an amino or substituted amino group.

Abstract: Certain appropriately substituted forms of pyrimidine and triazine are useful in the treatment to conditions associated with enhanced TGF&bgr; activity.