Synthesis of 5,6-dihydropyrrolo[2,1-a]isoquinolines featuring an intramolecular radical-oxidative cyclization of polysubstituted pyrroles, and evaluation of their cytotoxic activity.
A three-step protocol for the synthesis of 1,2,3,8,9-pentasubstituted-5,6-dihydropyrrolo[2,1-a]isoquinolines is described, using van Leusen's polysubstituted pyrrole construction followed by intramolecular radical-oxidative cyclization of the isoquinoline system. The cytotoxic activities of the dihydropyrroloisoquinolines were tested on six tumor cell lines. Preliminary structure-activity studies revealed the importance of the identity of the aromatic substituent at the C-2 position, particularly a phenyl, m-(amino) phenyl or m-(cyclohexylmethylpiperazinamide) phenyl substituent, for cytotoxic activity.
Reyes-Gutiérrez
Paul E
PE
Instituto de Química, Universidad Nacional Autónoma de México, Circuito Exterior, Ciudad Universitaria, México, D.F. 04510, México.
Camacho
José R
JR
Ramírez-Apan
Maria Teresa
MT
Osornio
Yazmin M
YM
Martínez
Roberto
R
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003500:Cyclization; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007546:Isoquinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D009369:Neoplasms / Q000188:drug therapy; D010084:Oxidation-Reduction; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D007546:Isoquinolines; D011758:Pyrroles