A New Type of Mixed Anhydride and Its Applications to the Synthesis of 7-Substituted 8-Chloro-5,5-dioxoimidazo[1,2-b][1,4,2]benzodithiazines with in Vitro Antitumor Activity
- 6 December 2001
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 45 (2), 430-437
- https://doi.org/10.1021/jm010953n
Abstract
A new series of 8-chloro-5,5-dioxoimidazo[1,2-b][1,4,2]benzodithiazine derivatives 8−25 with heteroaryloxycarbonyl or heteroarylcarbamoyl substituents at position 7 have been synthesized as potential antitumor agents. In this procedure a novel type of mixed anhydride 7 was prepared from 8-chloro-5,5-dioxoimidazo[1,2-b][1,4,2]benzodithiazine-7-carboxylic acid 6 and methanesulfonyl chloride, which in turn was condensed either with heteroarylamines or heteroarylhydroxy compounds. All the compounds prepared were screened at the National Cancer Institute (NCI) for their activities against a panel of 60 tumor cell lines, and relationships between structure and antitumor activity in vitro are discussed. The amides 8, 10, 12, 13, 21, and ester 25 were inactive, whereas the other compounds exhibited rather moderate activity against one or more human tumor cell lines. The prominent compound with remarkable activity (log GI50 < −8) and selectivity for the leukemia HL-60(TB) cell line was 2-methyl-8-quinolyl 8-chloro-5,5-dioxoimidazo[1,2-b][1,4,2]benzodithiazine-7-carboxylate 24.Keywords
This publication has 12 references indexed in Scilit:
- Carbonic anhydrase inhibitors: Sulfonamides as antitumor agents?Bioorganic & Medicinal Chemistry, 2001
- A Facile Synthesis and Chemical Properties of 3,4-Dihydro-2H-1,5,2-benzo[f]dithiazepin-3-ones with Potential Anticancer ActivityHETEROCYCLES, 2001
- Protease Inhibitors: Current Status and Future ProspectsJournal of Medicinal Chemistry, 2000
- Structure−Activity Relationships and Pharmacokinetic Analysis for a Series of Potent, Systemically Available Biphenylsulfonamide Matrix Metalloproteinase InhibitorsJournal of Medicinal Chemistry, 2000
- Tipranavir (PNU-140690): A Potent, Orally Bioavailable Nonpeptidic HIV Protease Inhibitor of the 5,6-Dihydro-4-hydroxy-2-pyrone Sulfonamide ClassJournal of Medicinal Chemistry, 1998
- 2-Mercaptobenzenesulphonamides as Novel Inhibitors of Human Immunodeficiency virus Type 1 Integrase and ReplicationAntiviral Chemistry and Chemotherapy, 1997
- 2-Sulfonyl-4-chloroanilino Moiety: A Potent Pharmacophore for the Anti-Human Immunodeficiency Virus Type 1 Activity of Pyrrolyl Aryl SulfonesJournal of Medicinal Chemistry, 1996
- Gradient-Based Editing of Proton Spectra According to Carbon-13 MultiplicitiesJournal of Magnetic Resonance, Series B, 1995
- Novel sulfonamides as potential, systemically active antitumor agentsJournal of Medicinal Chemistry, 1992
- Reaktionen der N‐Isocyan‐dialkylamineEuropean Journal of Organic Chemistry, 1965