RESUMO
In this study, the synthesis and potential enzyme interactions of new Pyrrolo[2,3-d]pyrimidine derivatives along with their inhibitory activity against SFK enzymes such as Fyn, Lyn, Hck, and c-Src were reported. The results indicated that compounds were slightly active of tested SFK enzymes in comparison with PP2 for Fyn, A-419259 for Lyn and CGP77675 for c-Src. Compound N-((2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)methyl)-4-(3,4-dimethoxyphenyl)butanamide (5) was identified as a non-selective slight inhibitor against Fyn, Lyn and c-Src. However, compounds did not show any inhibitory effects on Hck. Docking studies were performed to analyze the binding mode of compounds against SFKs. The best interaction was obtained between compound 5 and the active site of Fyn and c-Src enzymes in comparison with reference compounds PP2 and CGP77675, respectively.
Assuntos
Inibidores de Proteínas Quinases/farmacologia , Pirimidinas/farmacologia , Pirróis/farmacologia , Quinases da Família src/antagonistas & inibidores , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Humanos , Modelos Moleculares , Estrutura Molecular , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Pirimidinas/síntese química , Pirimidinas/química , Pirróis/síntese química , Pirróis/química , Relação Estrutura-Atividade , Quinases da Família src/metabolismoRESUMO
The title benzimidazole mol-ecule, C(8)H(8)N(4)O(2)·2H(2)O, is planar with a maximum deviation of 0.079â (2)â Å (for one of the O atoms in the nitro group). It crystallized as a dihydrate and inter-molecular O-Hâ¯O and N-Hâ¯O hydrogen bonds link the uncoordinated water mol-ecules, and the nitro and amine groups, respectively. In the crystal, N-Hâ¯O, O-Hâ¯N, O-Hâ¯O and C-Hâ¯O hydrogen bonds link the mol-ecules to form a three-dimensional network. A π-π contact between the benzene rings, [centroid-centroid distance = 3.588â (1)â Å] may further stabilize the crystal structure.
RESUMO
In the title compound, C(8)H(7)N(4)O(4) (+)·Cl(-), the cation possesses twofold symmetry, with the twofold axis bis-ecting the 2-methyl-5,6-dinitro-benzimidazolium cation. The methyl H atoms are disordered about this twofold axis and were assigned equal half-occupancies. The chloride anion also lies on a twofold axis. In the crystal, N-Hâ¯Cl and C-Hâ¯O hydrogen bonds link the ions to form a three-dimensional network.
