102121-55-1Relevant academic research and scientific papers
Design, synthesis and anticancer biological evaluation of novel 1,4-diaryl-1,2,3-triazole retinoid analogues of tamibarotene (AM80)
Aleixo, Mariana A. A.,Garcia, Taís M.,Carvalho, Diego B.,Viana, Luiz H.,Amaral, Marcos S.,Kassab, Najla M.,Cunha, Marilin C.,Pereira, Indiara C.,Guerrero, Palimécio G,Perdomo, Renata T.,Matos, Maria F. C.,Baroni, Adriano C. M.
, p. 109 - 124 (2018)
We report herein the design and synthesis via click chemistry of twelve novel triazole retinoid analogues of tamibarotene (AM80) and the evaluation of their anticancer activities against six cancer cell lines: HL60, K562, 786, HT29, MCF7 and PC3. Among the synthesized compounds, two were more potent than tamibarotene against solid tumor cells, and one of them had similar potency to tamibarotene against HL60 cells. The bioisosteric exchange between the amide group and the 1,2,3-triazole core in the retinoid agent tamibarotene (AM80) reported in this work is a valid strategy for the generation of useful compounds against cancer.
Design, synthesis and biological evaluation of novel tamibarotene derivative as multitarget anticancer agent
Jiang, Yuqi,Hou, Jinning,Li, Xiaoyang,Xu, Wenfang,Zhang, Yingjie
, p. 729 - 733 (2016/09/28)
A novel tamibarotene derivative was synthesized by coupling cytotoxic agent 5-Fluorouracil (5-FU) with tamibarotene via ester. This hybrid drug (compound 10) was evaluated for its antiproliferative activities against human leukemic U937, HL-60 and K562 cell lines in vitro. Results showed that compound 10 exhibited more potent anti-leukemic activity than the positive control tamibarotene. Furthermore, the preliminary stability test of compound 10 revealed that it could release tamibarotene and 5-FU significantly in vitro. These interesting results would be meaningful to develop more potent drugs for the treatment of human leukemia.
Palladium-catalyzed synthesis of aromatic carboxylic acids with silacarboxylic acids
Friis, Stig D.,Andersen, Thomas L.,Skrydstrup, Troels
supporting information, p. 1378 - 1381 (2013/04/24)
Aryl iodides and bromides were easily converted to their corresponding aromatic carboxylic acids via a Pd-catalyzed carbonylation reaction using silacarboxylic acids as an in situ source of carbon monoxide. The reaction conditions were compatible with a wide range of functional groups, and with the aryl iodides, the carbonylation was complete within minutes. The method was adapted to the double and selective isotope labeling of tamibarotene.
Design and synthesis of novel retinoid synergists having a dibenzodiazepine skeleton
Ohta, Kiminori,Kawachi, Emiko,Shudo, Koichi,Kagechika, Hiroyuki
scheme or table, p. 2465 - 2470 (2011/04/24)
Based on the structures of potent RXR agonists 2 and 3, novel dibenzodiazepine derivatives 4-6, containing two diphenylamine substructures, were designed as RXR modulator candidates and synthesized by utilizing Pd-catalyzed and Cu-promoted diphenylamine-generating reactions as key reactions. These compounds showed retinoid-synergistic activity, enhancing the HL-60 cell differentiation-inducing ability of the RAR agonist Am80. The Japan Institute of Heterocyclic Chemistry.
Selective alkylation of βII-tubulin and thioredoxin-1 by structurally related subsets of aryl chloroethylureas leading to either anti-microtubules or redox modulating agents
Fortin, Jessica S.,Cote, Marie-France,Lacroix, Jacques,Desjardins, Michel,Petitclerc, Eric,C.-Gaudreault, Rene
, p. 7277 - 7290 (2008/12/22)
Aryl chloroethylureas (CEUs) are potent anti-neoplastic agents alkylating specific intracellular proteins such as βII-tubulin. Recently we have identified a new subset of CEU derived from compound 36 that alkylates thioredoxin isoform 1 (Trx-1), inhibits the nuclear translocation of Trx-1, and favors the accumulation of cells in G0/G1 phase. We have evaluated the effects of various substituents and their position on the aromatic ring of a series of derivatives of 36 on (i) the anti-proliferative activity, (ii) the cell cycle progression, (iii) the nuclear translocation of Trx-1, and (iv) their covalent binding to β-tubulin. The same experiments were performed on representative CEU derivatives where the 2-chloroethyl amino moiety is replaced by either an ethyl, a 2-aminooxazolinyl or a 2-chloroacetyl group. On one hand, our results suggest that CEUs substituted on the phenyl ring at position 3 or 4 by cycloalkyl and substituted cycloalkyl or cycloalkoxy groups inhibit the nuclear translocation of Trx-1 and arrest the cell cycle progression in G0/G1. On the other hand, CEUs substituted by a fused aromatic ring, an aliphatic chain, or a fused aliphatic ring are alkylating βII-tubulin but not Trx-1. Beside the expected inactivity of the ethylurea derivatives, none of the modification to the electrophilic moiety led to cross-selectivity of the drugs toward β-tubulin but increased the anti-proliferative activity and resulted in mitigated effects on Trx-1 translocation.
Aza-retinoids as novel retinoid X receptor-specific agonists
Farmer, Luc J.,Marron, Kristen S.,Canan Koch, Stacie S.,Hwang,Kallel, E. Adam,Zhi, Lin,Nadzan, Alex M.,Robertson, Dave W.,Bennani, Youssef L.
, p. 2352 - 2356 (2007/10/03)
A new structurally simple series of potent lipophilic aza-retinoids RXR agonists has been developed. SAR studies for the N-alkyl-azadienoic acids described here demonstrate that the RXR activity profile is sensitive to the N-alkyl chain length. Further, we have expanded the work to include azadienoic acids, which exhibited many accessible conformations leading to a better understanding of the SAR around the series.
Tricyclic hydroxamate and benzaminde derivatives, compositions and methods
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Page/Page column 14-15; 38, (2008/06/13)
The present invention relates to compounds and methods for inhibiting histone deacetylase enzymatic activity. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit histone deacetylases (HDACs), and in the treatment of conditions mediated by HDAC, cancer, proliferative conditions, psoriasis, and also central nervous system diseases. It further deals with processes for preparing said compounds.
SUBSTITUTED ANTHRANILIC AMIDE DERIVATIVES AND METHODS OF USE
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Page 112, (2010/02/06)
Selected compounds are effective for prophylaxis and treatment of diseases, such as angiogenesis mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.
N-substituted heterocycles for the treatment of hypercholesteremia, dyslipidemia and other metabolic disorders; cancer, and other diseases
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, (2008/06/13)
The present invention relates to certain compounds of Formula (I) which can be useful in the treatment of diseases, such as, cancer, metabolic disorders, Type 2 Diabetes, dyslipidemia and/or hyperchloesterolemia:
