This invention relates to pyrimidine derivatives, processes for their preparation, pharmaceutical compositions, and their use in treating viral infections such as HCV or HBV.

This invention relates to pyrimidine derivatives, processes for their preparation, pharmaceutical compositions, and their use in treating viral infections such as HCV or HBV.

Compounds within the scope of the present invention have a Formula 1 ##STR00001##
or a salt or produg thereof, where ring A is selected from cycloaliphatic; ring B is aryl; R.sup.1 is selected from (C1-C10)alkyl, (C3-C10)cycloalkyl, halo, aryl, and heteroaryl; and R.sup.2 and R.sup.3 are independently selected from hydrogen and (C1-C6)alkyl. Disclosed compounds may have an IRAK4 IC.sub.50 of from 0.003 μM to 3.7 μM; a TAK1 IC.sub.50 of from 0.008 μM to 132 μM; and/or an IRAK4/TAK1 selectivity of from 1 to 450. Particular compounds may have an IRAK4/TAK1 selectivity of from 100 to 500. Disclosed compositions may be formulated as pharmaceutical compositions. A method for using the compounds and/or compositions also are disclosed. The method may comprise administering to a subject an effective amount of a compound within the scope of the present invention, particularly to selectively inhibit IRAK 1 and/or IRAK4 over TAK1.

Compounds within the scope of the present invention have a Formula 1 ##STR00001##
or a salt or produg thereof, where ring A is selected from cycloaliphatic; ring B is aryl; R.sup.1 is selected from (C1-C10)alkyl, (C3-C10)cycloalkyl, halo, aryl, and heteroaryl; and R.sup.2 and R.sup.3 are independently selected from hydrogen and (C1-C6)alkyl. Disclosed compounds may have an IRAK4 IC.sub.50 of from 0.003 μM to 3.7 μM; a TAK1 IC.sub.50 of from 0.008 μM to 132 μM; and/or an IRAK4/TAK1 selectivity of from 1 to 450. Particular compounds may have an IRAK4/TAK1 selectivity of from 100 to 500. Disclosed compositions may be formulated as pharmaceutical compositions. A method for using the compounds and/or compositions also are disclosed. The method may comprise administering to a subject an effective amount of a compound within the scope of the present invention, particularly to selectively inhibit IRAK 1 and/or IRAK4 over TAK1.

Inhibitors of erythrocyte band 3 tyrosine phosphorylation, compositions comprising same, and methods of using the inhibitors and compositions to treat sickle cell diseases.

Inhibitors of erythrocyte band 3 tyrosine phosphorylation, compositions comprising same, and methods of using the inhibitors and compositions to treat sickle cell diseases.

Use of a compound in preventing or treating a graft versus host disease (GVHD), especially use of the compound of formula (I) or a pharmaceutically acceptable salt thereof in preparing a drug for preventing or treating GVHD.

Formulations of Compound 1 or a pharmaceutically acceptable salt thereof are described. Also disclosed are capsules having a dry blended powder comprising Compound 1 or a pharmaceutically acceptable salt thereof. The Compound 1 or a pharmaceutically acceptable salt thereof may be a tartrate salt of Compound 1, such as a mono-, sub-, or di-tartrate salt, and including crystalline forms thereof. The formulations may include excipients such as diluents (e.g., microcrystalline cellulose, lactose); disintegrants (e.g., croscarmellose sodium); and lubricants (e.g., magnesium stearate).

##STR00001##

The use of glutamate 2b receptor antagonists and sigma receptor agonists as antitussives to treat or prevent a cough is disclosed. In preferred embodiments, the glutamate 2b receptor antagonist is ifenprodil or radiprodil. Preferred sigma receptor agonists include fluvoxamine, fluoxetine, excitalpram, and donepezil.

The present disclosure provides inhibitors of activin receptor-like kinase 5 (ALK5). Also disclosed are methods to modulate the activity of ALK5 and methods of treatment of disorders mediated by ALK5.