Synthesis of 1-(2-Aminophenyl)isoquinolines and the Biological Activity of Their cis-Dichloro Platinum(II) Complexes

• Published in: Journal of medicinal chemistry Vol. 42; no. 18; pp. 3478 - 3485
• Main Authors: von Nussbaum, Franz, Miller, Bernhard, Wild, Stefan, Hilger, Christoph S, Schumann, Susanne, Zorbas, Haralabos, Beck, Wolfgang, Steglich, Wolfgang
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 09-09-1999
• Subjects: Animals; Antineoplastic agents; Antineoplastic Agents - chemical synthesis; Biological and medical sciences; Cell Division - drug effects; DNA Replication - drug effects; General aspects; Isoquinolines - chemical synthesis; Isoquinolines - pharmacology; Leukemia L1210; Medical sciences; Mice; Models, Molecular; Molecular Structure; Pharmacology. Drug treatments; Platinum Compounds - chemical synthesis; Platinum Compounds - pharmacology; Tumor Cells, Cultured; Antineoplastic agent; Divalent metal Complexes; Nitrogen heterocycle; Cytotoxicity; DNA synthesis; Bidentate ligand; Amine; Chloro complex; Aromatic compound; Chemical synthesis; Platinum II Complexes; Isoquinoline derivatives; Rodentia; Organic ligand; Transition metal Complexes; In vitro; Biological activity; Cisplatin; L1210 cell line; Vertebrata; Mammalia; Cell line; Mouse; Platinoid Complexes; Inhibitor
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm980434t

The broad biological effects of isoquinolines prompted us to use them as chelating, nonleaving ligands in cis-platinum(II) antitumor complexes. The synthesis of several 1-(2-aminophenyl)isoquinoline derivatives with different levels of hydrogenation and varying substitution of the phenyl ring is reported. These compounds constitute a new class of ligands for the synthesis of oligocyclic platinum(II) complexes. In vitro cytotoxicity tests indicate that the most basic amine ligands afford the most effective complexes. Two of the new complexes were more potent against L1210 murine leukemia cells than the well-established antitumor compound cisplatinum.