Spleen tyrosine kinase (Syk) is a non-receptor-type tyrosine kinase which mediates diverse responses in haematopoietic cells. Therefore, Syk is an attractive therapeutic target, and in a study of Syk inhibitors as potentially new therapeutic agents, we discovered the 4-anilinopyrimidine-5-carboxamides. Enzyme screening indicated that an aminoethylamino moiety at the 2-position of the pyrimidine ring was important for Syk inhibitory activity, and an investigation of the substituents at the 4-position revealed that an anilino moiety substituted at the meta position was preferred. These compounds showed high selectivity for Syk, compared to other kinases, such as ZAP-70, c-Src, and PKC, and exhibited good inhibitory activities against 5-HT release from RBL-cells. Among them, compound 9a inhibited the passive cutaneous anaphylaxis reaction in mice, with an ID50 of 13 mg/kg following subcutaneous administration. These results suggest that our compounds are worthy of further evaluation as new anti-allergic agents.