Synthesis, pharmacophore modeling and in vitro activity of 10,11-dihydrodibenzo[b,f]oxepine-4-carboxamide derivatives as novel and potent antagonists of the prostaglandin EP4 receptor

Stasi, Luigi; Bhimani, Kanji; Borriello, Manuela; Canciani, Luca; Caselli, Gianfranco; Colace, F; Ferioli, Cristian; Kaswala, Mehul; Mennuni, Laura; Piepoli, Tiziana; Pucci, Sabrina; Salvi, Matteo; Shirsath, Vikas S.; Zanelli, Tiziano; Zerbi, Silvia

doi:10.1016/j.bmcl.2011.08.102

Cited by 3 publications

(1 citation statement)

References 30 publications

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“…Salicylamide analogue 21 was prepared from the Chan-Lam coupling 36 of methyl salicylate and 4-chlorophenyl boronic acid, providing the ether intermediate 20 in low yield, followed by ester hydrolysis and amidation (Scheme 4). Secondary phenyl anthranilamides 23a and 23b were assembled from Buchwald amination 37, 38 of triflated methyl salicylate and the appropriate aniline, followed by saponification/amidation.…”

Section: Chemistrymentioning

confidence: 99%

Discovery of anthranilamides as a novel class of inhibitors of neurotropic alphavirus replication

Barraza

Delekta

Sindac

et al. 2015

Bioorganic & Medicinal Chemistry

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Neurotropic alphaviruses are debilitating pathogens that infect the central nervous system (CNS) and are transmitted to humans via mosquitoes. There exist no effective human vaccines against these viruses, underlining the need for effective antivirals, but no antiviral drugs are available for treating infection once the viruses have invaded the CNS. Previously, we reported the development of novel indole-2-carboxamide-based inhibitors of alphavirus replication that demonstrate significant reduction of viral titer and achieve measurable brain permeation in a pharmacokinetic mouse model. Herein we report our continued efforts to improve physicochemical properties predictive of in vivo blood-brain barrier (BBB) permeability through reduction of overall molecular weight, replacing the indole core with a variety of aromatic and non-aromatic monocyclics. These studies culminated in the identification of simple anthranilamides that retain excellent potency with improved metabolic stability and significantly greater aqueous solubility. Furthermore, in a live virus study, we showed that two new compounds were capable of reducing viral titer by two orders of magnitude and that these compounds likely exert their effects through a mechanism similar to that of our indole-2-carboxamide inhibitors.

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Section: Chemistrymentioning

confidence: 99%

Discovery of anthranilamides as a novel class of inhibitors of neurotropic alphavirus replication

Barraza

Delekta

Sindac

et al. 2015

Bioorganic & Medicinal Chemistry

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ChemInform Abstract: Synthesis, Pharmacophore Modeling and in vitro Activity of 10,11‐Dihydrodibenzo[b,f]oxepine‐4‐carboxamide Derivatives as Novel and Potent Antagonists of the Prostaglandin EP₄ Receptor.

Stasi¹

2012

ChemInform

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Expedient Pd‐Catalyzed α‐Arylation towards Dibenzoxepinones: Pivotal Manske's Ketone for the Formal Synthesis of Cularine Alkaloids

et al. 2020

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Synthesis, pharmacophore modeling and in vitro activity of 10,11-dihydrodibenzo[b,f]oxepine-4-carboxamide derivatives as novel and potent antagonists of the prostaglandin EP4 receptor

Cited by 3 publications

References 30 publications

Discovery of anthranilamides as a novel class of inhibitors of neurotropic alphavirus replication

Discovery of anthranilamides as a novel class of inhibitors of neurotropic alphavirus replication

ChemInform Abstract: Synthesis, Pharmacophore Modeling and in vitro Activity of 10,11‐Dihydrodibenzo[b,f]oxepine‐4‐carboxamide Derivatives as Novel and Potent Antagonists of the Prostaglandin EP₄ Receptor.

Expedient Pd‐Catalyzed α‐Arylation towards Dibenzoxepinones: Pivotal Manske's Ketone for the Formal Synthesis of Cularine Alkaloids

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Synthesis, pharmacophore modeling and in vitro activity of 10,11-dihydrodibenzo[b,f]oxepine-4-carboxamide derivatives as novel and potent antagonists of the prostaglandin EP4 receptor

Cited by 3 publications

References 30 publications

Discovery of anthranilamides as a novel class of inhibitors of neurotropic alphavirus replication

Discovery of anthranilamides as a novel class of inhibitors of neurotropic alphavirus replication

ChemInform Abstract: Synthesis, Pharmacophore Modeling and in vitro Activity of 10,11‐Dihydrodibenzo[b,f]oxepine‐4‐carboxamide Derivatives as Novel and Potent Antagonists of the Prostaglandin EP4 Receptor.

Expedient Pd‐Catalyzed α‐Arylation towards Dibenzoxepinones: Pivotal Manske's Ketone for the Formal Synthesis of Cularine Alkaloids

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Product

Resources

About

ChemInform Abstract: Synthesis, Pharmacophore Modeling and in vitro Activity of 10,11‐Dihydrodibenzo[b,f]oxepine‐4‐carboxamide Derivatives as Novel and Potent Antagonists of the Prostaglandin EP₄ Receptor.