Substituted diaminopyrimidyl compounds, compositions thereof, and methods of treatment therewith

Disclosed herein are alkylheteroaryl-diaminopyrimidyl compounds of the general formula (I), wherein the substituents are as defined in the specification. The disclosed compounds selectively inhibit PKC-theta without affecting the other members of the PKC family such as PKC-delta and/or PKC-eta. Also disclosed is the use of compounds of formula (I) for the treatment of PKC-theta mediated disorders such as graft-versus-host disease, organ transplant rejection, psoriasis, Duchenne muscular dystrophy, rheumatoid arthritis, diabetes, insulin resistance, myasthenia gravis,multiple sclerosis, colitis, psoriatic arthritis, ankylosing spondylitis, atopic dermatitis, Sjogren syndrome, asthma, or lupus. Examples of a compound of formula (I) are: 2-(((4-(2,2-Difluoropropoxy)pyrimidin-5-yl)methyl)amino)-4-(((1R,4S)-4-hydroxy-3,3-dimethylcyclohexyl)amino)pyrimidine-5-carbonitrile 4-(((1S,4R)-4-Hydroxy-3,3-dimethylcyclohexyl)amino)-2-((2-(5-methyl-1Htetrazol-1-yl)benzyl)amino)pyrimidine-5-carbonitrile (1S,3R)-3-(2-((4-Isopropylpyrimidin-5-yl)methylamino)-5-(trifluoromethyl)pyrimidin-4-ylamino)-2,2-dimethylcyclobutanol 3-(((5-Cyano-4-(((1s,4s)-4-hydroxy-4-methylcyclohexyl)amino)pyrimidin-2-yl)amino)methyl)-4-(trifluoromethyl)pyridine 1-oxide