N-alkyl-[1,1′-biphenyl]-2-sulfonamide derivatives as novel broad spectrum anti-epileptic drugs with efficacy equivalent to that of sodium valproate

Tanaka, Tomoyuki; Yajima, Nana; Kiyoshi, Tomoko; Miura, Yoshiki; Iwama, Seiji

doi:10.1016/j.bmcl.2017.07.037

Cited by 6 publications

(2 citation statements)

References 8 publications

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“…Researchers at Sumimoto Dainippon Pharma are also currently developing new AEDs based on the scaffold of benzenesulphonamide such as 2'-fluoro-N-methyl-[1,1'-biphenyl]-2-sulphonamide and other N-alkyl-[1,1'-biphenyl]-2-sulphonamide derivatives 28 , 29 . In addition, a few groups designed and evaluated substituted 4-aminobenzene sulphonamides, relying on Lipinski rule or hCA I inhibitors as potential novels AEDs 30 , 31 .…”

Section: Discussionmentioning

confidence: 99%

Stereoselective pharmacokinetic and pharmacodynamic analysis of a CNS-active sulphamoylphenyl carbamate derivative

Bibi

Shusterman

Nocentini

et al. 2019

Journal of Enzyme Inhibition and Medicinal Chemistry

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3-Methylpentyl(4-sulphamoylphenyl)carbamate (MSPC) came as the most potent compound out of a new series of carbamates composed of phenyl-ethanol or branched aliphatic alcohols, and 4-benzenesulphonamide-carbamic acid. In this study, the anticonvulsant activity and pharmacokinetics (PKs) of MSPC-two individual enantiomers were comparatively analysed in rats as well as their carbonic anhydrase (CA) inhibition. The anticonvulsant activity of MSPC enantiomers was evaluated at the rat-maximal electroshock (MES) test, and their CA inhibition evaluated. (R)-MSPC had a 29% higher clearance and consequently, a lower plasma exposure area under the curve (AUC) than (S)-MSPC and racemic-MSPC. Nevertheless, (R)-MSPC had a better brain permeability than its (S)-enantiomer with brain-to-plasma-(AUC)-ratio (BPR) of 2.07 ((R)-enantiomer), 1.85 (racemate), and 0.79 ((S)-enantiomer). As a whole body ( in vivo ) pharmacodynamic (PD) measure, MSPC-anticonvulsant maximal electroshock seizure (MES) activity was less enantioselective than MSPC-CA inhibition. The lack of significant differences between racemic-MSPC and its individual enantiomers suggest that their anticonvulsant activity might be due to multiple mechanisms of action.

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Section: Discussionmentioning

confidence: 99%

Stereoselective pharmacokinetic and pharmacodynamic analysis of a CNS-active sulphamoylphenyl carbamate derivative

Bibi

Shusterman

Nocentini

et al. 2019

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…As a result, DSP-0565 has been identified to be a broad-spectrum antiseizure candidate. The investigators initially found that 2 -fluoro-N-methyl-[1,1 -biphenyl]-2sulfonamide showed potent ASM activities in a number of seizure screening models, but its reactive metabolite led to the risk of unfavorable idiosyncratic toxicity [77]. To diminish reactive metabolite production, they identified an alternative polar group and optimized N-methylsulfonamide moiety in the previous lead compound.…”

Section: -(2 -Fluoro-[11 -Biphenyl]-2-yl)acetamide (Dsp-0565mentioning

confidence: 99%

Identification of New Antiseizure Medication Candidates in Preclinical Animal Studies

Yang,

Wu,

Lai

et al. 2023

IJMS

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Epilepsy is a multifactorial neurologic disease that often leads to many devastating disabilities and an enormous burden on the healthcare system. Until now, drug-resistant epilepsy has presented a major challenge for approximately 30% of the epileptic population. The present article summarizes the validated rodent models of seizures employed in pharmacological researches and comprehensively reviews updated advances of novel antiseizure candidates in the preclinical phase. Newly discovered compounds that demonstrate antiseizure efficacy in preclinical trials will be discussed in the review. It is inspiring that several candidates exert promising antiseizure activities in drug-resistant seizure models. The representative compounds consist of derivatives of hybrid compounds that integrate multiple approved antiseizure medications, novel positive allosteric modulators targeting subtype-selective γ-Aminobutyric acid type A receptors, and a derivative of cinnamamide. Although the precise molecular mechanism, pharmacokinetic properties, and safety are not yet fully clear in every novel antiseizure candidate, the adapted approaches to design novel antiseizure medications provide new insights to overcome drug-resistant epilepsy.

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Identification of 2-(2′-fluoro-[1,1′-biphenyl]-2-yl)acetamide as a Sodium Valproate-like broad spectrum anti-epileptic drug candidate

Tanaka

Yajima

Kiyoshi

et al. 2019

Bioorganic & Medicinal Chemistry Letters

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N-alkyl-[1,1′-biphenyl]-2-sulfonamide derivatives as novel broad spectrum anti-epileptic drugs with efficacy equivalent to that of sodium valproate

Cited by 6 publications

References 8 publications

Stereoselective pharmacokinetic and pharmacodynamic analysis of a CNS-active sulphamoylphenyl carbamate derivative

Stereoselective pharmacokinetic and pharmacodynamic analysis of a CNS-active sulphamoylphenyl carbamate derivative

Identification of New Antiseizure Medication Candidates in Preclinical Animal Studies

Identification of 2-(2′-fluoro-[1,1′-biphenyl]-2-yl)acetamide as a Sodium Valproate-like broad spectrum anti-epileptic drug candidate

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