2894-45-3Relevant articles and documents
10-(4-Phenylpiperazine-1-carbonyl)acridin-9(10H)-ones and related compounds: Synthesis, antiproliferative activity and inhibition of tubulin polymerization
Waltemate, Jana,Ivanov, Igor,Ghasemi, Jahan B.,Aghaee, Elham,Daniliuc, Constantin Gabriel,Müller, Klaus,Prinz, Helge
supporting information, (2020/11/27)
As part of our continuing search for potent inhibitors of tubulin polymerization, two novel series of 42 10-(4-phenylpiperazine-1-carbonyl)acridin-9(10H)-ones and N-benzoylated acridones were synthesized on the basis of a retrosynthetic approach. All newly synthesized compounds were tested for antiproliferative activity and interaction with tubulin. Several analogs potently inhibited tumor cell growth. Among the compounds tested, 10-(4-(3-methoxyphenyl)piperazine-1-carbonyl)acridin-9(10H)-one (17c) exhibited excellent growth inhibitory effects on 93 tumor cell lines, with an average GI50 value of 5.4 nM. We were able to show that the strong cytotoxic effects are caused by disruption of tubulin polymerization, as supported by the EBI (N,N'-Ethylenebis(iodoacetamide)) assay and the fact that the most potent inhibitors of cancer cell growth turned out to be the most efficacious tubulin polymerization inhibitors. Potencies were nearly comparable or superior to those of the antimitotic reference compounds. Closely related to this, the most active analogs inhibited cell cycling at the G2/M phase at concentrations down to 30 nM and induced apoptosis in K562 leukemia cells. We believe that our work not only proves the excellent suitability of the acridone scaffold for the design of potent tubulin polymerization inhibitors but also enables synthetic access to further potentially interesting N-acylated acridones.
Synthesis of 3-Sulfonylamino Quinolines from 1-(2-Aminophenyl) Propargyl Alcohols through a Ag(I)-Catalyzed Hydroamination, (2 + 3) Cycloaddition, and an Unusual Strain-Driven Ring Expansion
Kumar, Yalla Kiran,Kumar, Gadi Ranjith,Reddy, Thota Jagadeshwar,Sridhar, Balasubramanian,Reddy, Maddi Sridhar
supporting information, p. 2226 - 2229 (2015/05/13)
We describe herein a silver-catalyzed conversion of 1-(2-aminophenyl)-propargyl alcohols to 4-substituted 3-tosylaminoquinolines using TsN3 as an amino surrogate. Controlled reactions reveal the pathway consisting of Ag(I)-catalyzed 5-exo-dig cyclization, catalyst-free (2 + 3) cycloaddition, and ring-expansive rearrangement via nitrogen expulsion. As a support study, we show that the cyclic enamines in similar conditions produce amidines via a C - C bond migration. (Chemical Equation Presented).
Synthesis of N,N-dialkyl-9-oxoacridine-10(9H)-carbothioamides via the reaction of (2-halophenyl)(2-isothiocyanatophenyl)methanones with secondary amines, followed by cyclization with NaH
Kobayashi, Kazuhiro,Nakagawa, Kazuhiro,Yuba, Shohei
, p. 2033 - 2039 (2013/12/04)
The first preparation of acridin-9(10H)-ones carrying a tertiary thiocarbamoyl group at C(10), i.e., N,N-dialkyl-9-oxoacridine-10(9H)- carbothioamides 9, is described. The method is based on the reaction of (2-halophenyl)(2-isothiocyanatophenyl)methanones 7, prepared from (2-aminophenyl)(2-halophenyl)methanones 5 by a convenient three-step sequence, with secondary amines in DMF at room temperature to generate the corresponding thiourea derivatives 8 in situ, which are treated with NaH at 100-120° to provide the desired products in one-pot reactions in generally good yields.
