| abstract |
2-Aminopyrimidine compounds are described, which are useful as modulators of the H4 receptor; Such compounds can be used in pharmaceutical compositions and methods for the treatment of disease states, disorders and conditions mediated by the activity of the H4 receptor such as allergy, asthma, autoimmune diseases and pruritus. 1. A chemical entity selected from compounds of the formula (I): wherein R 1 is: a) a C 1-6 alkyl group, optionally substituted with -OH, -C 1-4 alkyl, -CF 3, or -O - (monocyclic cycloalkyl); b) a benzyl, -CH2- (monocyclic heteroaryl) or phenethyl group, each optionally substituted with halogen; c) a monocyclic cycloalkyl group, - (CH2) 0-1-tetrahydrofuranyl, or - (CH2) 0-1-tetrahydropyranyl, each optionally fused to a phenyl ring, and each optionally substituted with C1-4 alkyl or phenyl; or d) an adamantyl group; R2 is H, F, methyl or methoxy; or R1 and R2 taken together form - (CH2) 3-5- or - (CH2) 2OCH2-; and -N (R3) R4 is one of the following acyclic, monocyclic, spirocyclic, bridge or fused ring systems: where q is 0 or 1; R3 and R4 are taken together as defined by the structure of each of said portions; Ra is H or OH; Rb and Rc are each independently H or C1-3 alkyl; and each substituent Rd is methyl or two substituents Rd taken together form a methylene or ethylene bridge; provided that when R1 is methyl, then -N (R3) R4 is selected from said spirocyclic, bridged and fused ring systems; and pharmaceutically acceptable salts of compounds of the formula (I), pharmaceutically acceptable prodrugs of compounds of the formula (I), and pharmaceutically acceptable metabolites of the formula (I). |