Pyrimidine derivatives useful as selective COX-2 inhibitors

本发明提供了式(I)化合物，其中：R#+[1]是选自H、C#-[1-6]烷基、被1-5个氟原子取代的C#-[1-2]烷基，C#-[3-6]链烯基、C#-[3-10]环烷基C#-[0-6]烷基、C#-[4-12]桥连的环烷基、A(CR#+[4]R#+[5])n和B(CR#+[4]R#+[5])n；R#+[2]是被1-5个氟原子取代的C#-[1-2]烷基；R#+[3]是选自C#-[1-6]烷基、NH#-[2]和R#+[7]CONH；R#+[4]和R#+[5]独立地选自H或C#-[1-6]烷基；A是未被取代的5或6元杂芳基或未被取代的6元芳基，或是被1个或多个R#+[6]取代的5或6元杂芳基或6元芳基；R#+[6]是选自卤素、C#-[1-6]烷基、被1个或多个氟原子取代的C#-[1-6]烷基、C#-[1-6]烷氧基、被一个或多个氟原子取代的C#-[1-6]烷基、NH#-[2]SO#-[2]和C#-[1-6]烷基SO#-[2]；B是选自式(i)和式(ii)组成的基团，其中(iv)限定了该环的连接点；R#+[7]是选自H、C#-[1-6]烷基、C#-[1-6]烷氧基、C#-[1-6]烷基OC#-[1-6]烷基、苯基、HO#-[2]CC#-[1-6]烷基、C#-[1-6]烷基OCOC#-[1-6]烷基、C#-[1-6]烷基OCO、H#-[2]NC#-[1-6]烷基、C#-[1-6]烷基OCONHC#-[1-6]烷基和C#-[1-6]烷基、CONHC#-[1-6]烷基；n是0至4。式(I)化合物是COX-2的有效的选择性抑制剂，可用于治疗多种症状和疾病的疼痛、发热及发炎。 The invention provides the compounds of formula (I) in which:R1 is selected from the group consisting of H, C1-6alkyl, C1-2alkyl substituted by one to five fluorine atoms, C3-6alkenyl, C3-6alkynyl, C3-10cycloalkylC0-6alkyl, C4-12bridged cycloalkyl, A(CR4R5)n and B(CR4R5)n;R2 is C1-2alkyl substituted by one to five fluorine atoms;R3 is selected from the group consisting of C1-6alkyl, NH2 and R7CONH;R4 and R5 are independently selected from H or C1-6alkyl;A is an unsubstituted 5- or 6-membered heteroaryl or an unsubstituted 6-membered aryl, or a 5- or 6-membered heteroaryl or a 6-membered aryl substituted by one or more R6;R6 is selected from the group consisting of halogen, C1-6alkyl, C1-6alkyl substituted by one more fluorine atoms, C1-6alkoxy, C1-6alkoxy substituted by one or more F, NH2SO2 and C1-6alkylSO2;B is selected from the group consisting of where defines the point of attachment of the ring;R7 is selected from the group consisting of H, C1-6alkyl, C1-6alkoxy, C1-6alkylOC1-6alkyl, phenyl, HO2CC1-6alkyl, C1-6alkylOCOC1-6alkyl, C1-6alkylOCO, H2NC1-6alkyl, C1-6alkylOCONHC1-6alkyl and C1-6alkylCONHC1-6alkyl; andn is 0 to 4.Compounds of formula (I) are potent and selective inhibitors of COX-2 and are of use in the treatment of the pain, fever and inflammation of a variety of conditions and diseases.