Synthesis of 4(3H)quinazolinimines with selective cytotoxic effect on human acute promyelocytic leukemia cells.

We synthesized a new family of six 4(3H)quinazolinimines based on the reaction between (E)-N-(2-cyanophenyl)benzimidoyl chloride and substituted anilines reaching the formation of their corresponding C2, N3-substituted quinazoliniminium chlorides. This method provides novel, direct and flexible access to diverse substituted 4(3H)quinazolinimines. New compounds obtained following the proposed synthesis were fully characterized and, including the thirteen 4(3H)quinazolinimines synthesized by this method and previously reported by us, were used to study its cytotoxic effect on neoplastic cell lines. The mechanism involved in cell toxicity was also studied. Results showed that these compounds were highly cytotoxic, in particular on Human Promyelocytic Leukemia cells (HL60) and Chronic Myelogenous Leukemia cells (K562) when compared with conventional antineoplastic drugs such as etoposide and cisplatin. The mechanism associated to cytotoxic effect was mainly apoptosis, which not was decreased by antioxidant addition, thereby suggesting that the compounds exert apoptotic death through a mechanism unrelated with oxidative stress.

Synthesis of 4(3H)quinazolinimines by reaction of (E)-N-(aryl)-acetimidoyl or -benzimidoyl chloride with amines.

An efficient one-step method to access 4(3H)quinazolinimines by reaction of phenylchloroimines with 2-aminobenzonitrile is described. The reaction of (E)-N-(2-cyanophenyl)benzimidoyl chloride with substituted anilines that yields a number of their corresponding C2, N3-substituted quinazoliniminium chlorides or neutral products is also reported. These methods provide direct and flexible access to diverse substituted iminoquinazolines substituted at the C2, N3-positions. All the new compounds were fully characterized and six examples are given with their single-crystal X-ray structure.

Half-sandwich rhodium and iridium complexes containing homochiral imidazolyl-imine ligands: synthesis, characterization and catalytic applications.

Condensation of homochiral primary amines with 1-methyl-1H-imidazole-2-carbaldehyde affords the corresponding imidazolyl-imine compounds (L1-L3) which have been employed as ligands for the preparation of half-sandwich rhodium and iridium complexes of the formula [(η(5)-C5Me5)MClLn][SbF6]. Treatment of these chloride compounds with AgSbF6 renders dicationic aqua-complexes [(η(5)-C5Me5)MLn(H2O)] [SbF6]2 which act as catalysts for the Diels-Alder reaction between methacrolein and cyclopentadiene. Catalysis occurs with good exo:endo selectivity and poor enantioselectivity. All the compounds have been completely characterized by analytical and spectroscopic methods. Characterization includes the molecular structure determination of the complexes [(η(5)-C5Me5)MClLn][SbF6] (Ln = L1, M = Rh, (1) Ir (4); Ln = L3, M = Ir (6)) and [(η(5)-C5Me5)ML1(H2O)][SbF6]2 (M = Rh (7), Ir (10)) using X-ray diffraction. From the stereochemical properties of the organometallic precursors the catalytic outcome is discussed.