Acridine and its derivatives: a patent review (2009 – 2013)

Abstract

Thousands of acridines with therapeutic and biological activities or with photochemical properties have been developed. In addition, to modify the position and the nature of the substituent on the acridine core, more attention may be paid to the development of azaacridine or other heteroatom-substituted acridine derivatives and their synthesis methods to broaden the application of acridine derivatives. In cancer chemotherapy, the mode of action of acridine derivatives needs to be further studied. Efficient methods for identification and optimization of acridine derivatives to localize at the sites of disease need to be further developed. Moreover, acridine drugs may be combined with such bioactive agents as DNA repair proteins inhibitors to overcome tumor resistance and improve outcomes.

Cross‐Coupling of α‐Carbonyl Sulfoxonium Ylides with C−H Bonds

“…M oreover,t he quinoline 23 a was obtained in 77 %y ield by cross-coupling of 22 and 2b and was then converted into the benz[c]acridine 24 a in one step and 60 % yield, after treatment with acatalytic amount of [{Cp*IrCl 2 } 2 ] in am ixture of isopropanol and water (Scheme 1). [17] In apreliminary study of the mechanism of the C À Hcrosscoupling of sulfoxonium ylides,w ec ould verify that using either [{Cp*RhCl 2 } 2 ](2mol %), 1 (4 mol %), or 3 (4 mol %) as the rhodium source under the optimized reaction conditions led to similar yields of 6a (17-20 %a fter 1h,7 2-77 %a fter 17 h), which suggests that these rhodium complexes are all kinetically competent pre-catalysts of the reaction. Although serenditipitous,t his two-step sequence was also amenable to the synthesis of 24 b and 24 c in good overall yields.S ignificantly,t his approach offers an attractive alternative to the harsh reaction conditions typically used for the synthesis of benz[c]acridines, [16] am otif frequently explored in drug discovery.…”

Synthesis of novel acridine bis-sulfonamides with effective inhibitory activity against the carbonic anhydrase isoforms I, II, IX and XII

“…8 Well-known drugs containing the acridine moiety include Amsacrine, Asulacrine, Acronycine, Acridine carboxamide (DACA), Proflavine and Ascididemin (Chart 1), and they have been used as anti-cancer or anti-bacterial agents. 12,13 Furthermore, many acridine sulfonamides are known as strong carbonic anhydrase (CA, EC 4.2.1.1) inhibitors (CAIs), potentially useful for the treatment glaucoma 9,10 or other conditions, which the activity of the CA isoforms are deregulated.…”

“…[11][12][13] This diversity of roles makes different isoforms interesting drug targets for a variety of conditions. [1,10]phenanthrolin-9-one; CAIs, carbonic anhydrase inhibitors; IR, infrared; NMR, nuclear magnetic resonance; HRMS, high resolution mass spectroscopy; SAR, structure-activity relationship; DMSO, dimethyl sulfoxide; LC, liquid chromatography; DBSA, p-dodecylbenzenesulfonic acid; TLC, tine layer chromatography; mp, melting point; Lit, literature; ESI, electron spray ionization; TEA, trimethylamine; lM, micromolar; nM, nanomolar; K I , inhibition constant.…”

Biomimetic One-Pot Route to Acridine Epoxides

“…6 A key feature of these molecules is the planar base structure, which allows strong but reversible intercalation into DNA chains between nitrogen bases 7 and inhibition of topoisomerase enzymes. 8 More recently, the antibacterial activity has been ascribed to their activity as amphiphilic membrane disruptors.…”