One‐Pot Synthesis of Novel Antiproliferative 9‐Aminoacridines

Abstract

Highly efficient one-pot syntheses of antiproliferative 9-aminoacridine (9-AA) derivatives are described. Simple S N Ar and addition/elimination reactions, using readily accessible starting materials, give a fast entry to novel 9-(pyridylamino)-acridines, 9-(pyrimidinylamino)acridines and potential

Small Molecule Binds with Lymphocyte Antigen 6K to Induce Cancer Cell Death

“…The reaction was stirred at r.t. for 4 h. Afterwards, ethyl acetate (EtOAc) (≈50 mL) was added to form a precipitate, which was collected by filtration. The solid was redissolved in methanol (MeOH) at 45 • C, reprecipitated with EtOAc, and filtered to yield a yellow solid (1.22 g, 78%) [22,23]. 1 Second step-synthesis of N1-(acridin-9-yl)-2-methoxybenzene-1,4-diamine (2): 1 (0.800 g, 2.32 mmol) and a catalytic amount of Pd/C were added to 100 mL MeOH in a pressure flask.…”

“…The resulting suspension was agitated under 50 psi of H 2 for 2 h. The suspension was then filtered to remove the Pd/C. The filtrate was evaporated under reduced pressure to yield the crude product as a yellow solid (0.730 g, 99%), which was carried on without further purification [22,23]. 1 Third step-synthesis of NSC243928: N1-(acridin-9-yl)-2-methoxybenzene-1,4-diamine from step 2 (0.228 g, 0.723 mmol) and dry pyridine (0.086 mL, 1.06 mmol) were added to 3.6 mL of dry dichloromethane (DCM).…”

Expedient synthesis and anticancer evaluation of dual‐action 9‐anilinoacridine methyl triazene chimeras

“…Previously, we reported on the S N Ar reaction of electrophilic haloaryls bearing one or two strongly electron-withdrawing groups to obtain antiproliferative 9-AnA derivatives (also dubbed: "reverse" approach) (Gellerman et al, 2010(Gellerman et al, , 2011. Here, we employed a similar synthetic strategy to obtain two new molecular chimeras.…”

“…In the past, we developed the highly efficient one‐pot derivatization of 9‐anilonoacridines (9‐AAs) at the amino group by simple S N Ar reaction using easily accessible haloaryl starting materials (Gellerman, Gaisin, & Brider, 2010; Gellerman, Waintraub, Albeck, & Gaisin, 2011). Such a “reverse” approach (Figure 2) to synthesize 9‐AnAs complements the “classical” electrophilic aromatic substitution (EAS) approach to 9AnA derivatives, in which 9‐Cl acridine reacts with substituted anilines (Redko, Albeck, & Gellerman, 2012).…”

Pd-catalyzed one-pot approach for installation of 9-aminoacridines via Buchwald-Hartwig amination and cycloaromatization

“…[1][2] Among them, 9-aminoacridine is a featured structural motif in medicinally relevant compounds and synthetic drugs (Figure 1). [3][4][5][6][7] It has been well-known that 9-aminoacridine derivatives possess versatile biological properties such as anti-Alzheimer, antibacterial, anti-BVDV, anticancer, anti-inflammatory, antiproliferative, antimalarial and antituberculous activities, [8][9][10][11][12][13][14][15] and has also been studied for DNA and RNA intercalating properties. [16][17][18] 9-Aminoacridine derivatives and related compounds have been used as dyes, pigments, corrosion inhibitors, and electrode materials for rechargeable lithium-ion batteries.…”