Montmorillonite K-10 catalyzed cyclization of N-ethoxycarbonyl-N′-arylguanidines: Access to pyrimido[4,5-c]carbazole and pyrimido[5,4-b]indole derivatives

• Published in: Bioorganic & medicinal chemistry letters Vol. 20; no. 14; pp. 4244 - 4247
• Main Authors: Debray, Julien, Zeghida, Walid, Baldeyrou, Brigitte, Mahieu, Christine, Lansiaux, Amélie, Demeunynck, Martine
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 15.07.2010; Elsevier
• Subjects: Antineoplastic agents; Bentonite - chemistry; Biological and medical sciences; Carbazole; Carbazoles - chemistry; Catalysis; Cell Line, Tumor; Chemical Sciences; Cyclization; DNA binding; Friedel–Crafts; General aspects; Guanidines - chemistry; Humans; Indole; Indoles - chemistry; Medical sciences; Nitrogen heterocycles; Pharmacology. Drug treatments; Topoisomerase; Friedel–Crafts; Topoisomerase; Nitrogen heterocycles; Carbazole; Indole; DNA binding; Antineoplastic agent; Nitrogen heterocycle; Cytotoxicity; Isomerases; Friedel Crafts reaction; Aromatic compound; Tumor cell; Human; Promyelocytic leukemia; Intramolecular reaction; Clay; Catalytic reaction; Montmorillonite; Enzyme; DNA topoisomerase; Tetracyclic compound; Tricyclic compound; In vitro; Biological activity; HL60 cell line; Biological fixation; Cell line; Cyclization; Tertiary amine; Friedel-Crafts
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2010.05.028

Two new heterocycles, pyrimido[4,5-c]carbazole and pyrimido[5,4-b]indole, were prepared in three steps from 3-aminocarbazole and 3-aminoindole, respectively. The key Friedel–Crafts intramolecular cyclization was realized under microwave irradiation using montmorillonite K-10 clay as a catalyst. The pyrimido[4,5-c]carbazole derivative shows significant micromolar IC50 against cancer cell lines. Unlike similar carbazole and indolocarbazole compounds, the molecule does not interfere with topoisomerase activity.