Synthesis and murine antineoplastic activity of bis[(carbamoyloxy)methyl] derivatives of pyrrolo[2,1-a]isoquinoline.
The synthesis of 4,5-dihydropyrrolo[2,1-a]isoquinolines is reported. A key intermediate in the synthesis of 8-methoxy-4,5-dihydropyrrolo[2,1-a]isoquinolines, 6-hydroxy-1,2,3,4-tetrahydroisoquinoline-1-carboxylic acid (6), was prepared by using a regiospecific phenolic cyclization reaction. The P388 lymphocytic activity is reported for 1,2-bis(hydroxymethyl)-5,6-dihydro-8-methoxy-3-methylpyrrolo [2,1-a]isoquinoline bis(isopropylcarbamate) (11a), 1,2-bis(hydroxymethyl)-5,6-dihydro-8-methoxy-3-methylpyrrolo[2,1-a ]isoquinoline bis(cyclohexylcarbamate) (11b), 1,2-bis(hydroxymethyl)-5,6-dihydro-3-methylpyrrolo[2,1-a]isoqui nol ine bis(methylcarbamate) (13a), 1,2-bis(hydroxymethyl)-5,6-dihydro-3-methylpyrrolo [2,1-a]isoquinoline bis(ethylcarbamate) (13b), and 1,2-bis(hydroxymethyl)-5,6-dihydroxy-3-methylpyrrolo[2,1-a]isoq uin oline bis(cyclohexylcarbamate) (13c); all of the compounds were active. Compound 11a was tested in an expanded tumor panel and was shown to be active against B16 melanocarcinoma, CD8F1 mammary, L1210 lymphoid leukemia, colon 38, and MX-1 human tumor breast xenograft systems.
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D001943:Breast Neoplasms / Q000473:pathology; D002219:Carbamates / Q000138:chemical synthesis* / Q000633:toxicity; D055598:Chemical Phenomena; D002621:Chemistry; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000633:toxicity; D007941:Leukemia P388 / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy; D011758:Pyrroles / Q000138:chemical synthesis* / Q000633:toxicity; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship; D014183:Transplantation, Heterologous
D000970:Antineoplastic Agents; D002219:Carbamates; D007546:Isoquinolines; D011758:Pyrroles