Discovery of 2-substituted benzoxazole carboxamides as 5-HT3 receptor antagonists

Yang, Zan; Fairfax, David J.; Maeng, Jun‐Ho; Masih, Liaqat; Usyatinsky, Alexander; Hassler, Carla; Isaacson, Soshanna; Fitzpatrick, Kevin; DeOrazio, Russell J.; Harding, J. Patrick; Isherwood, Matthew; Dobritsa, Svetlana V.; Christensen, Kevin L.; Wierschke, Jonathan D.; Bliss, Brian I.; Peterson, Lisa H.; Beer, Cathy M.; Cioffi, Christopher; Lynch, Michael; Rennells, W. Martin; Richards, Justin J.; Rust, Timothy; Khmelnitsky, Yuri L.; Cohen, Marlene L.; Manning, David D.

doi:10.1016/j.bmcl.2010.09.038

Cited by 15 publications

(7 citation statements)

References 16 publications

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“…Similarly, previous studies have shown that arylbenzoxazoles possess anti-inflammatory,17,18 and anticancer activities 19–21. In fact, it has been recently shown that arylbenzoxazoles have potential anti-UC properties 22. In addition, the presence of the amino group, together with the carboxylate in compound 1, possibly decreases the absorption due to zwitterion formation.…”

Section: Discussionmentioning

confidence: 74%

“…Arylbenzoxazoles are reported to have a wide range of pharmacological activities that includes anti-inflammatory17,18 and anticancer activities 19–21. Also, a recent study showed that arylbenzoxazoles have the potential to treat IBD by acting as an antagonist at the serotonin subtype 3 receptor 22. Based on the above argument, 4-aminophenylbenzoxazol-2-yl-5-acetic acid was selected for synthesis and evaluated as a carrier of 5-ASA via azo linkage.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis and evaluation of mutual azo prodrug of 5-aminosalicylic acid linked to 2-phenylbenzoxazole-2-yl-5-acetic acid in ulcerative colitis

Jilani¹,

Shomaf²,

Alzoubi³

2013

DDDT

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In this study, the syntheses of 4-aminophenylbenzoxazol-2-yl-5-acetic acid, (an analogue of a known nonsteroidal anti-inflammatory drug [NSAID]) and 5-[4-(benzoxazol-2-yl-5-acetic acid)phenylazo]-2-hydroxybenzoic acid (a novel mutual azo prodrug of 5-aminosalicylic acid [5-ASA]) are reported. The structures of the synthesized compounds were confirmed using infrared (IR), hydrogen-1 nuclear magnetic resonance (1H NMR), and mass spectrometry (MS) spectroscopy. Incubation of the azo compound with rat cecal contents demonstrated the susceptibility of the prepared azo prodrug to bacterial azoreductase enzyme. The azo compound and the 4-aminophenylbenzoxazol-2-yl-5-acetic acid were evaluated for inflammatory bowel diseases, in trinitrobenzenesulfonic acid (TNB)-induced colitis in rats. The synthesized diazo compound and the 4-aminophenylbenzoxazol-2-yl-5-acetic acid were found to be as effective as 5-aminosalicylic acid for ulcerative colitis. The results of this work suggest that the 4-aminophenylbenzoxazol-2-yl-5-acetic acid may represent a new lead for treatment of ulcerative colitis.

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Section: Discussionmentioning

confidence: 74%

Section: Introductionmentioning

confidence: 99%

Synthesis and evaluation of mutual azo prodrug of 5-aminosalicylic acid linked to 2-phenylbenzoxazole-2-yl-5-acetic acid in ulcerative colitis

Jilani¹,

Shomaf²,

Alzoubi³

2013

DDDT

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“…[177] Aminobenzoxazole carboxamide-basedc ompounds 130, 131,a nd 132 were also discovered as potent 5-HT3 receptor antagonists for the treatment of diarrhea-predominant irritable bowels yndrome (IBS-D,F igure 57). [178] All three compounds were active when administered orally to mice and blocked the 5-HT-induced transient bradycardia (Table 16). The 5-HT 3 receptor ligands have been explored in the past to treat conditions such as nausea, vomiting, irritable bowels yndrome, alcohol addiction, and inflammatory reactions.…”

Section: Other Therapeutic Targetsmentioning

confidence: 99%

Recent Advances in the Development of Pharmacologically Active Compounds that Contain a Benzoxazole Scaffold

et al. 2015

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In recenty ears, the emergence of biologically active compounds that contain ah eterocyclic ring has gained ag reat deal of attention among medicinal chemists. Among these, benzoxazole-based compounds are particularly attractive because of their wide range of pharmacological activities. In this focus review, we highlight recent advancements in the development of benzoxazole-based pharmacologically active compounds since the year 2000.

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“…For background to our work to design and synthesize a series of potent 5-HT 3 receptor antagonists, see: Bermudez et al (1990); Vernekar et al (2010); Yang et al (2010).…”

Section: Related Literaturementioning

confidence: 99%

4-Methyl-N-(9-methyl-9-azabicyclo[3.3.1]non-3-yl)benzamide

Lv¹,

Yan²,

Dong³

et al. 2012

Acta Cryst E

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Discovery of 2-substituted benzoxazole carboxamides as 5-HT3 receptor antagonists

Cited by 15 publications

References 16 publications

Synthesis and evaluation of mutual azo prodrug of 5-aminosalicylic acid linked to 2-phenylbenzoxazole-2-yl-5-acetic acid in ulcerative colitis

Synthesis and evaluation of mutual azo prodrug of 5-aminosalicylic acid linked to 2-phenylbenzoxazole-2-yl-5-acetic acid in ulcerative colitis

Recent Advances in the Development of Pharmacologically Active Compounds that Contain a Benzoxazole Scaffold

4-Methyl-N-(9-methyl-9-azabicyclo[3.3.1]non-3-yl)benzamide

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