Pyrimidine derivative Compound, Process for preparing the pharmaceutical composition containing same and use of said compound in the manufacture of a Medicament useful in the treatment of cancer

摘要

A pyrimidine derived compound of formula (1): wherein ring A is an imidazo [1,2a] pyrid-3-yl or a pyrazolo [2,3a] pyrid-3-yl; R2 is attached to a carbon ring and is selected from the group consisting of halo, nitro, cyano, hydroxyl, trifluoromethyl, trifluoromethoxy, amino, carboxyl, carbamoyl, mercapto, sulfamoyl, C1-6 alkyl, C2-6 alkenyl, C2- alkynyl 6, C1-6 alkoxy, C1-6 alkanoyl, C1-6 alkanoyloxy, N- (C1-6 alkyl) amino, N, N- (C1-6 alkyl) 2 amino, C1-6 alkanoylamino, N- (C1 alkyl -6) carbamoyl, N, N- (C1-6 alkyl) 2 carbamoyl, C1-6 alkyl S (O) where a is 0 to 2, C1-6 alkoxycarbonyl, N- (C1-6 alkyl) sulfamoyl, N, N- (C1-6alkyl) 2 sulfamoyl, phenyl,Acyclic group, phenylethanol or (acyclic group) sulfur; in any C1-6, alquenilo c2-6, acrylonitrile c2-6, phenyl or heterocyclic group, one or more G may be selected to replace carbon; if the acyclic group contains a terminal kernel nitrogen group, one group may be selected to replace carbon. Select from group Q; m is 0-5; R2 may be the same or different; R1 is selected independently from group oxo, halo, halo, Nico, Ciano, hidroxilo, trifluorometyl, trifluoroxilo, amino, carboxilo, carbamoyilo, mercato, sulamoilo, c1-3 tar, alquenilo C2-3, D;hydroxyl, trifluoromethyl, trifluoromethoxy, amino, carboxyl, carbamoyl, mercapto, sulfamoyl, C1-6 alkyl, C2-6 alkenyl, C1-6 alkynyl, C1-6 alkanoyl, C1-6 alkanoyloxy, N- (alkyl C1-6) amino, N, N- (C1-6 alkyl) 2 amino, C1-6 alkanoylamino, N- (C1-6 alkyl) carbamoyl, N, N- (C1-6 alkyl) 2 carbamoyl, C1- alkyl 6 S (O) a where a is 0 to 2, C1-6 alkoxycarbonyl, C1-6 alkoxycarbonylamino, benzyloxycarbonylamino, N- (C1-6 alkyl) sulfamoyl and N, N- (C1-6 alkyl) 2 sulfamoyl, where any C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or phenyl can optionally be substituted on carbon by one or more K; q is 0-2;where the values of R4 can be the same or different and where p + q is less than or equal to 5; G, J and K are independently selected from halo, nitro, cyano, hydroxyl, trifluoromethoxy, trifluoromethyl, amino, carboxyl, carbamoyl, mercapto, sulfamoyl, methyl, ethyl, methoxy, ethoxy, acetyl, acetoxy, methylamino, ethylamino, dimethylamino , diethylamino, N-methyl-N-ethylamino, acetylamino, N-methylcarbamoyl, N-ethylcarbamoyl, N, N-dimethylcarbamoyl, N, N-diethylcarbamolyl, N-methyl-N-ethylcarbamoyl, methylthiol, ethylthiol, methylsulfinyl, ethylsulfyl , ethylsulfonyl, methoxycarbonyl, ethoxycarbonyl, N-methylsulfamoyl, N-ethylsulfamoyl, N, N-dimethylsulfamoyl,N, N-diethylsulfamoyl or N-methyl-N-ethylsulfamoyl; and Q and R are independently selected from C1-4alkyl, C1-4alkanoyl, C1-4alkylsulfonyl, N- (C1-4alkyl) carbamoyl, N, N- (C1-4alkyl) 2 carbamoyl, benzyl, benzyloxycarbonyl, benzoyl, and phenylsulfonyl; C2-3 alkynyl, C1-3 alkoxy, C1-3 alkanoyl, N- (C1-3 alkyl) amino, N, N- (C1-2 alkyl) 2 amino, C1-3 alkanoylamino, N- (C1-3 alkyl ) carbamoyl, N, N- (C1-2alkyl) 2 carbamoyl, C1-3alkyl S (O) a where a is 0 to 2, N- (C1-3alkyl) sulfamoyl and N, N- (C1alkyl -3) 2 sulfamoyl where any C1-2 alkyl, C1-3 alkyl,C2-3 alkenyl or C2-3 alkynyl can optionally be substituted on carbon by one or more J; n is 0 to 2; where the values of R1 can be the same or different; ring B is a phenyl or phenyl fused to a C5-7 cycloalkyl ring; R3 is halo, nitro, cyano, hydroxyl, amino, carboxyl, carbamoyl, mercapto, sulfamoyl, C2-6 alkenyl, C2-6 alkynyl; p is 0-4; where the R3 values can be the same or different; R4 is an A-E- group;A selected from C1-6 tar, phenyl, a non periodic, cyclopropyl compound C3-8, phenyl C1-6 tar (non periodic) C1-6 or cyclopropyl compound C3-8 C1-6; C1-6 tar, phenyl, a non periodic, cyclopropyl compound C3-8, phenyl C1-6, C1-6 tar or C3-8 cyclopropyl compound C1-6 may be replaced by one or more D in carbon; if this non periodic group contains trace nitrogen, it can be replaced by a group selected by group R; E is a direct combination, or -,-C (O) --OC (o)..-That's it.-N (Ra) C (O) --C (O) N (Ra) --N (RA)..-S (O) r--SO2N (Ra) - o N (Ra) SO2-Where R is one or more C1-6 optional hydrocarbon or asphalt substituted by D, R is 0-2; or an acceptable salt for drug use or an ester that can be dissolved in vivo. It also describes the formulation compounds (1) used in the 500 yuan inhibition of cell cycle of CDK2, CDK4 and Cdk6. The pharmaceutical ingredients used to prepare the formula compounds are listed in detail (1).