Aminopyrimidines as syk inhibitors

The present provides pyrimidine amines of formula (1) that are potent inhibitors of spleen tyrosine kinase, and are useful in the treatment and prevention of diseases mediated by said enzyme, such as asthma, COPD and rheumatoid arthritis. Pharmaceutical compositions Claim 1: A compound of formula (1) or a pharmaceutically acceptable salt thereof, wherein: p is 0 to 4; q is 0, 1 or 2; Cy is selected from C4-7 cycloalkyl, oxetanyl, pyrrolidinyl, piperidinyl and azepanyl; R1 is selected from H, C1-4 alkyl, C1-4 haloalkyl, C3-6 cycloalkyl and O-C1-4 alkyl; R4 is selected from H, C1-4 alkyl and C3-4 cycloalkyl; Ry (a) is aminomethyl, OH, OCH3, OCH2CH2OH, F, CN, CO2Ra (a), CONRb (a) Rc (a), NRa (a) Ra (a), NHC (O) C1-3 alkyl (optionally substituted with OH), NHC (O) NH2, NHSO2NH2, NHSO2-C1-3 alkyl, or NHSO2-C1-3 haloalkyl; Rz (a) is selected from (A) C1-4 alkyl optionally substituted with one to three groups independently selected from OH, NH2, CN, CO2Ra (a) and CONH2, (B) C1-3 fluoroalkyl, (C) halogen, (D) CN, (E) CO-C1-4 alkyl (optionally substituted with one or two groups independently selected from ORa (a), CN, CO2Ra (a), CONRa (a) Ra (a) and NRa (a) Ra (a)), (F) CO-phenyl (optionally substituted with one or two groups independently selected from ethynyl, CO2Ra (a), CN, F and OH), (G) C3-6 CO-cycloalkyl (optionally substituted with OH or CO2Ra (a)), (H) C0-3-CO2Ra (a), (I) -C (O) NRb (a) Rc (a) , (J) -ORa (a), (K) -OC (O) Ra (a), (L) -NRb (a) Rc (a), (M) -NHC (O) C1-4 alkyl (optionally substituted with one to three OH or a CONRa (a) Ra (a)), (N) -NHSO2-C1-3alkyl, (O) -NHSO2NH2, (P) oxo, (Q) 1,3,4-oxadiazole -2 (3H) -one, (R) 1,2,4-oxadiazol-5 (4H) -one, (S) SO2NH2, (T) SO2-C1-3 alkyl, (U) SO2-C1-3 haloalkyl , and (V) SO2Ph; Ra (a) H or C1-4 alkyl; Rb (a) and Rc (a) are independently selected from (A) H, (B) C3-6 cycloalkyl optionally substituted with OH, (C) heteroaryl selected from imidazolyl, pyridyl and indolyl, (D) tetrahydrofuranoyl, (E) benzyl, (F) phenyl optionally substituted with one or two groups independently selected from (CH2) 0-2OH and F, (G1) C1-4 alkyl and (G2) C1-4 haloalkyl, wherein each of (G1) and (G2) is optionally substituted with one to three groups independently selected from (i) OH, (ii) C3-6 cycloalkyl optionally substituted with one or two groups independently selected from C1-4 alkyl , CONH2, CO2H and CH2OH, (iii) CONH2, (iv) SO2NH2, (v) SO2-C1-4 alkyl, (vi) 4- to 7-membered monocyclic heterocyclyl optionally substituted with one or two groups independently selected from oxo, ( CH2) 0-2OH and C1-4 alkyl, (vii) a 5- or 6-membered heteroaryl optionally substituted with one or two groups independently selected from carboxy, (CH2) 0-2OH and C1-4 alkyl, (viii) CN, (ix) O-C1-4 alkyl, ( x) CO2H, (xi) NRa (a) -C1-4C alkyl (O), (xii) phenyl optionally substituted with one or two groups independently selected from (CH2) 0-2OH, SO2NH2, CF3, F and Cl, ( xiii) 1-pyrrolidinyl optionally substituted with oxo, (xiv) 1-imidazolidinyl optionally substituted with oxo, (xv) 1-piperidinyl optionally substituted with oxo, and (xvi) 4-morpholinyl; or Rb (a) Rc (a) together with the nitrogen atom to which they are attached form a 6 or 7 membered heterocycle having an additional 0 to 1 heteroatom selected from N, O and S, where said heterocycle is optionally substituted with one or two groups independently selected from oxo, CN, (CH2) 0-2OH, acetyl, benzyl, SO2-C1-4 alkyl, CONH2, methoxymethyl, carboxymethyl, CO2Ra (a) and C1-4 alkyl.