Potential Anxiolytic Agents. Part 4: Novel Orally-Active N5-Substituted Pyrido[1,2-a]benzimidazoles with High GABA-A Receptor Affinity

Jordan, Alfonzo D.; Vaidya, Anil H.; Rosenthal, Daniel I.; Dubinsky, Barry; Kordik, Cheryl P.; Sanfilippo, Pauline J.; Wu, Wu‐Nan; Reitz, Allen B.

doi:10.1016/s0960-894x(02)00463-8

Cited by 32 publications

(12 citation statements)

References 7 publications

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“…A number of heterocyclic N‐substituted piperazine derivatives and other piperazine derivatives have anti‐viral activities and have been used for treatment of nervous system disorders [Blair et al, ; Jordan et al, ]. Several anti‐cancer compounds containing a quinoxaline ring have been reported as well [Shoemaker, ; Rigas et al, ; Monge et al, ; Miller et al, ; Corbett et al, ; Gali‐Muhtasib et al, ; Diab‐Assef et al, ; Gao et al, ; Undevia et al, ; Kakodkar et al, ; Noolvi et al, ].…”

mentioning

confidence: 99%

A Novel Anti‐Cancer Agent, 1‐(3,5‐Dimethoxyphenyl)‐4‐[(6‐Fluoro‐2‐Methoxyquinoxalin‐3‐yl)Aminocarbonyl] Piperazine (RX‐5902), Interferes With β‐Catenin Function Through Y593 Phospho‐p68 RNA Helicase

Kost

Yang

et al. 2015

J of Cellular Biochemistry

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1-(3,5-Dimethoxyphenyl)-4-[(6-fluoro-2-methoxyquinoxalin-3-yl)aminocarbonyl] piperazine (RX-5902) exhibits strong growth inhibition in various human cancer cell lines with IC50 values ranging between 10 and 20 nM. In this study, we demonstrate that p68 RNA helicase is a cellular target of RX-5902 by the drug affinity responsive target stability (DARTS) method, and confirmed the direct binding of (3) H-labeled RX-5902 to Y593 phospho-p68 RNA helicase. We further demonstrated RX-5902 inhibited the β-catenin dependent ATPase activity of p68 RNA helicase in an in vitro system. Furthermore, we showed that treatment of cancer cells with RX-5902 resulted in the downregulation of the expression of certain genes, which are known to be regulated by the β-catenin pathway, such as c-Myc, cyclin D1 and p-c-Jun. Therefore, our study indicates that the inhibition of Y593 phospho-p68 helicase - β-catenin interaction by direct binding of RX-5902 to Y593 phospho-p68 RNA helicase may contribute to the anti-cancer activity of this compound.

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mentioning

confidence: 99%

A Novel Anti‐Cancer Agent, 1‐(3,5‐Dimethoxyphenyl)‐4‐[(6‐Fluoro‐2‐Methoxyquinoxalin‐3‐yl)Aminocarbonyl] Piperazine (RX‐5902), Interferes With β‐Catenin Function Through Y593 Phospho‐p68 RNA Helicase

Kost

Yang

et al. 2015

J of Cellular Biochemistry

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“…On the other hand, compound III was synthesized by an efficient solid‐phase reaction via N ‐acyliminium ion cyclization‐nucleophilic addition under mild reaction conditions using commercially available starting materials . Compound IV was synthesized by Jordan et al as a GABA‐A receptor through five steps . Therefore, environmentally friendly and cost‐effective conditions for constructing functioned benzimidazoles with short reaction steps and simple work‐up procedures would still be attractive to chemists.…”

Section: Introductionmentioning

confidence: 99%

One‐pot synthesis of benzimidazole‐pyrazines and their anticancer activities

Wei

Bai

et al. 2019

Journal of Heterocyclic Chem

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The skeleton of fused benzimidazole‐pyrazine was constructed via an Ugi/deprotection/cyclization (UDC) and hydroamination cascade reaction. This four‐step reaction was carried out in a one‐pot procedure with only one‐time column chromatography purification. The representative compound 7b exhibited 67% cell growth inhibitory activity against human breast cancer cell line MDA‐MB‐453 at the concentration of 10μM.

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“…Furthermore, pyrrolobenzimidazoles, 9 pyridobenzimidazoles, 10 were found to be useful in treating central nervous system disorder. Pyridobenzimidazoles have also anxiolytic activity in humans, [11][12][13] and pyrimidobenzimidazoles were anti-rheumatic agents. 14 Also, 1,2,4-triazinobenzimidazoles were found to be aldose reductase inhibitors 15 and to possess antimicrobial activity.…”

Section: Introductionmentioning

confidence: 99%

Recent advances on the synthesis of azoles, azines and azepines fused to benzimidazole

Dawood¹,

Elwan²,

Abdel‐Wahab³

2011

Arkivoc

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Potential Anxiolytic Agents. Part 4: Novel Orally-Active N5-Substituted Pyrido[1,2-a]benzimidazoles with High GABA-A Receptor Affinity

Cited by 32 publications

References 7 publications

A Novel Anti‐Cancer Agent, 1‐(3,5‐Dimethoxyphenyl)‐4‐[(6‐Fluoro‐2‐Methoxyquinoxalin‐3‐yl)Aminocarbonyl] Piperazine (RX‐5902), Interferes With β‐Catenin Function Through Y593 Phospho‐p68 RNA Helicase

A Novel Anti‐Cancer Agent, 1‐(3,5‐Dimethoxyphenyl)‐4‐[(6‐Fluoro‐2‐Methoxyquinoxalin‐3‐yl)Aminocarbonyl] Piperazine (RX‐5902), Interferes With β‐Catenin Function Through Y593 Phospho‐p68 RNA Helicase

One‐pot synthesis of benzimidazole‐pyrazines and their anticancer activities

Recent advances on the synthesis of azoles, azines and azepines fused to benzimidazole

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