Chapter 2. Anticonvulsant Agents

Liebman, Jeffrey M.; Schneider, Jennifer

doi:10.1016/s0065-7743(08)61028-3

Cited by 8 publications

(2 citation statements)

References 94 publications

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“…(C16H18N203) C, , N. Compound 4b: yield 0.72 g (32%); mp 216-218 °C (recrystallized from EtOAc); [ ]26^= +0.3 ± 0.1°(c = 1, MeOH); Rf 0.27 (2% MeOH/CHCIg); IR (KBr) 3250,1620(KBr) 3250, ,1520(KBr) 3250, ,1440(KBr) 3250, ,1360(KBr) 3250, ,1270(KBr) 3250, , 1230(KBr) 3250, .1140(KBr) 3250, .1000 NMR (DMSO-de) 1.36 (d, J = 6.9 Hz, 3 ), 1.90 (s, 3 ), 4.85-5.00 (m, 1 H), 5.64 (d, J = 8.2 Hz, 1 ), 6.16 (s, 1 H), 6.38 (s, 1 ), 7.20-7.29 (m, 5 H), 7.59 (s, 1 H), 8.53 (d, J = 8. 2 Hz, 1 H), 8.72 (d, J = 7.8 Hz, 1 H), addition of (R)-(-)-mandelic acid to a CDC13 solution of 4b gave only one signed for the acetyl methyl protons; 13C NMR (DMSO-dg) 22.32, 22.50,48.03, 50.64,107.20,110.41,125.75 (2 C), 126.59,128.14 (2 C), 142.48,144.19,151.38,166.92,169.02 ppm.…”

Section: Methodsmentioning

confidence: 99%

“…Our earlier discovery that the dianion (2) prepared from glutarimide (1) and sodium amide in liquid ammonia reacted with electrophiles such as alkyl halides, aldehydes, ketones, and esters exclusively at the carbanion site provided a convenient, one-step route to 2-substituted glu- (6) Witiak, D. T.; Seth, S. K.; Baizman, E. R.; Weibel, S. L.; Wolf, . H. J.…”

Section: Methodsmentioning

confidence: 99%

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Preparation and anticonvulsant activity of a series of functionalized .alpha.-aromatic and .alpha.-heteroaromatic amino acids

Kohn¹,

Kn²,

P³

et al. 1990

J. Med. Chem.

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We recently reported the potent anticonvulsant activity of (R,S)-alpha-acetamido-N-benzyl-alpha-phenylacetamide (2b). Selectively substituted derivatives of this compound have now been prepared (23 examples) and evaluated in the maximal electroshock seizure (MES) and horizontal screen (tox) tests in mice. In several key cases, replacement of the alpha-phenyl substituent in 2b by a relatively small, electron-rich, heteroaromatic moiety led to a substantial improvement in the anticonvulsant potency of the drug candidate. The most active compounds were (R,S)-alpha-acetamido-N-benzyl-2-furanacetamide (2g) and (R,S)-alpha-acetamido-N-benzyl-2-pyrroleacetamide (2i). After ip administration, the MES ED50 values for 2g (10.3 mg/kg) and 2i (16.1 mg/kg) compared well with phenytoin (9.50 mg/kg). Evaluation of the two individual enantiomers of 2g demonstrated that the anticonvulsant activity resided in the R stereoisomer. The low ED50 value (3.3 mg/kg) for (R)-2g contributed to the large protective index (TD50/ED50) observed for this drug candidate, which approached that of phenytoin.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Preparation and anticonvulsant activity of a series of functionalized .alpha.-aromatic and .alpha.-heteroaromatic amino acids

Kohn¹,

Kn²,

P³

et al. 1990

J. Med. Chem.

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The Significance of the Imidazole Ring in Anticonvulsant Activity of (Arylalkyl)imidazoles

Calis

Dalkara

Ertan

et al. 1988

Archiv der Pharmazie

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The imidazole ring in nafimidone I 1 -(2-naphthyl)-2-( 1 -imidazolyl)ethan-one1 was substituted with various grouos to investigate the significance Die Rolle des Imidazolrings in antikonvulsiv wirksamen (Arylalky1)imidazolen -.--Der Imidazolring von NafimidonI 1 -(2-naphthyl)-2-( 1 -imidazolyl)ethanonl wurde durch verschiedene Gruppen substituiert und die Rolle des Imidazolrings auf die antikonvulsive Wirkung untersucht. Dazu wurden einige 2-Acetylnaphthaline und ihre reduzierten Derivate synthetisiert. Als Reduktionsmittel wurde NaBH, verwendet. Die antikonvulsiven Eigenschaften dieser Verbindungen wurden mit Phase I Tests eines Pro-of the imidazole ring in anticonvulsant activity. For this purpose, some 2acetylnaphthalene derivatives and their reduction products were synthesized. Several N-alkylation methods were used to prepare 2-acetylnaphthalenes. NaBH, was used to synthesize their reduction products. Anticonvulsant activities of these compounds were determined by phase I tests of Antiepileptic Drug Development Programme.gramms zur Entwicklung antikonvulsiver Arzneistoffe bestimmt.Although there are a number of antiepileptic drugs available in the market, the development of more efficient compounds with less toxicity is still Arch. Pharm. (Weinheim) 321,841-846 (1988) 0 VCH Verlagsgesellschaft mbH, 0-6940 Weinheim. 1988 0365-6233/88/1212-0841$02.5OfO

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Synthesis and Evaluation of Anticonvulsant and Antimicrobial Activities of 3‐Hydroxy‐6‐methyl‐2‐substituted 4H‐Pyran‐4‐one Derivatives

Aytemir

Calis

Özalp

2004

Archiv der Pharmazie

102

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In this study, thirteen 3-hydroxy-6-methyl-2-substituted 4H-pyran-4-one derivatives were synthesized for the evaluation of their potential anticonvulsant activity. Mannich bases were prepared by the reaction of substituted piperazine derivatives with allomaltol and formaline. The structures of the synthesized compounds were confirmed by IR, (1)H-NMR and elemental analysis. Their anticonvulsant activities were determined in vivo by maximal electroshock (MES), sub-cutaneous Metrazol (scMet), and rotorod toxicity tests for neurological deficits. The antimicrobial activities of the synthesized compounds were investigated in vitro against some bacteria and fungi using the microdilution broth method. Ac-cording to the activity studies, 3-hydroxy-6-methyl-2-[4-(2-trifluoromethyl-phenyl)-piperazin-1-ylmethyl]-4H-pyran-4-one (3i) was the compound determined to be most active in the scMet test for all doses at four hours and for the 300 mg/kg dose at half an hour. 2-[4-(4-Chloro-phenyl)-piperazin-1-ylmethyl]-3-hydroxy-6-methyl-4H-pyran-4-one (3f) was found to be protective against MES whereas 2-chlorophenyl derivative (3e) was not. Looking at the antifungal activity results, compounds 3b, 3h, and 3i were determined to have activity against all fungi.

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Chapter 2. Anticonvulsant Agents

Cited by 8 publications

References 94 publications

Preparation and anticonvulsant activity of a series of functionalized .alpha.-aromatic and .alpha.-heteroaromatic amino acids

Preparation and anticonvulsant activity of a series of functionalized .alpha.-aromatic and .alpha.-heteroaromatic amino acids

The Significance of the Imidazole Ring in Anticonvulsant Activity of (Arylalkyl)imidazoles

Synthesis and Evaluation of Anticonvulsant and Antimicrobial Activities of 3‐Hydroxy‐6‐methyl‐2‐substituted 4H‐Pyran‐4‐one Derivatives

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