Facile formation of hydrophilic derivatives of 5H-8,9-dimethoxy-5-[2-(N,N-dimethylamino)ethyl]-2,3-methylenedioxydibenzo[c,h] [1,6]naphthyridin-6-one (ARC-111) and its 12-aza analog via quaternary ammonium intermediates.
Several new TOP1-targeting agents were prepared using as intermediates the N,N,N-trimethyl quaternary ammonium salts of either ARC-111 or its 12-aza analog (ARC-31), 3 and 4, respectively. Direct displacement of the quaternary ammonium group with water, imidazole, alkylethylenediamines, or polyhydroxylated alkylamines provides a convenient means for furthering the structure-activity relationships associated with these non-camptothecin TOP1-targeting agents.
Feng
Wei
W
Department of Pharmaceutical Chemistry, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854-8020, USA.
Satyanarayana
Mavurapu
M
Tsai
Yuan-Chin
YC
Liu
Angela A
AA
Liu
Leroy F
LF
Lavoie
Edmond J
EJ
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004264:DNA Topoisomerases, Type I / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D051379:Mice; D015394:Molecular Structure; D009287:Naphthyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000644:Quaternary Ammonium Compounds / Q000737:chemistry*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D023041:Xenograft Model Antitumor Assays
C530871:12-aza-5H-8,9-dimethoxy-5-(2-(N,N-dimethylamino)ethyl)-2,3-methylenedioxydibenzo(c,h)(1,6)naphthyridin-6-one; D000970:Antineoplastic Agents; D009287:Naphthyridines; D000644:Quaternary Ammonium Compounds; C481982:topovale; D004264:DNA Topoisomerases, Type I