Synthesis and anticonvulsant activity of aromatic tetramethylcyclopropanecarboxamide derivatives

Jakob Avi Shimshoni; Meir Bialer; Boris Yagen

doi:10.1016/j.bmc.2008.03.051

Synthesis and anticonvulsant activity of aromatic tetramethylcyclopropanecarboxamide derivatives

Jakob Avi Shimshoni
, Meir Bialer
, Boris Yagen^*

^*Corresponding author for this work

School of Pharmacy

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

Abstract

As part of our ongoing research on potential new antiepileptic drugs (AEDs), a series of tetramethylcyclopropanecarboxamide derivatives containing benzene ring were designed, synthesized, and evaluated for anticonvulsant activities in the murine maximal electroshock (MES) and subcutaneous pentylenetetrazole (scMet) seizure tests. The most potent compound emerging from this study was N-(2,2,3,3-tetramethylcyclopropanecarboxamide)-p-phenyl-sulfonamide (21), possessing an ED₅₀ value of 26 mg/kg in the rat-MES test and a remarkable PI (PI = TD₅₀/ED₅₀) value above 19. The better anticonvulsant potency of compound 21 and its wider safety margin compared to valproic acid (VPA) and zonisamide make it a potential candidate to become a new AED second-generation to VPA.

Original language	English
Pages (from-to)	6297-6305
Number of pages	9
Journal	Bioorganic and Medicinal Chemistry
Volume	16
Issue number	11
DOIs	https://doi.org/10.1016/j.bmc.2008.03.051
State	Published - 1 Jun 2008

Keywords

2,2,3,3-Tetramethylcyclopropanecarboxylic acid
Anticonvulsants
Maximal electroshock seizure test
Phenyl-alkyl-amines
Structure-activity relationships
Subcutaneous pentylenetetrazole seizure test
Sulfonamides
Valproic acid

Access to Document

10.1016/j.bmc.2008.03.051

Cite this

@article{b83a23a88f034119a8cb0774aa0617a3,

title = "Synthesis and anticonvulsant activity of aromatic tetramethylcyclopropanecarboxamide derivatives",

abstract = "As part of our ongoing research on potential new antiepileptic drugs (AEDs), a series of tetramethylcyclopropanecarboxamide derivatives containing benzene ring were designed, synthesized, and evaluated for anticonvulsant activities in the murine maximal electroshock (MES) and subcutaneous pentylenetetrazole (scMet) seizure tests. The most potent compound emerging from this study was N-(2,2,3,3-tetramethylcyclopropanecarboxamide)-p-phenyl-sulfonamide (21), possessing an ED50 value of 26 mg/kg in the rat-MES test and a remarkable PI (PI = TD50/ED50) value above 19. The better anticonvulsant potency of compound 21 and its wider safety margin compared to valproic acid (VPA) and zonisamide make it a potential candidate to become a new AED second-generation to VPA.",

keywords = "2,2,3,3-Tetramethylcyclopropanecarboxylic acid, Anticonvulsants, Maximal electroshock seizure test, Phenyl-alkyl-amines, Structure-activity relationships, Subcutaneous pentylenetetrazole seizure test, Sulfonamides, Valproic acid",

author = "Shimshoni, \{Jakob Avi\} and Meir Bialer and Boris Yagen",

year = "2008",

month = jun,

day = "1",

doi = "10.1016/j.bmc.2008.03.051",

language = "אנגלית",

volume = "16",

pages = "6297--6305",

journal = "Bioorganic and Medicinal Chemistry",

issn = "0968-0896",

publisher = "Elsevier Ltd.",

number = "11",

}

TY - JOUR

T1 - Synthesis and anticonvulsant activity of aromatic tetramethylcyclopropanecarboxamide derivatives

AU - Shimshoni, Jakob Avi

AU - Bialer, Meir

AU - Yagen, Boris

PY - 2008/6/1

Y1 - 2008/6/1

N2 - As part of our ongoing research on potential new antiepileptic drugs (AEDs), a series of tetramethylcyclopropanecarboxamide derivatives containing benzene ring were designed, synthesized, and evaluated for anticonvulsant activities in the murine maximal electroshock (MES) and subcutaneous pentylenetetrazole (scMet) seizure tests. The most potent compound emerging from this study was N-(2,2,3,3-tetramethylcyclopropanecarboxamide)-p-phenyl-sulfonamide (21), possessing an ED50 value of 26 mg/kg in the rat-MES test and a remarkable PI (PI = TD50/ED50) value above 19. The better anticonvulsant potency of compound 21 and its wider safety margin compared to valproic acid (VPA) and zonisamide make it a potential candidate to become a new AED second-generation to VPA.

AB - As part of our ongoing research on potential new antiepileptic drugs (AEDs), a series of tetramethylcyclopropanecarboxamide derivatives containing benzene ring were designed, synthesized, and evaluated for anticonvulsant activities in the murine maximal electroshock (MES) and subcutaneous pentylenetetrazole (scMet) seizure tests. The most potent compound emerging from this study was N-(2,2,3,3-tetramethylcyclopropanecarboxamide)-p-phenyl-sulfonamide (21), possessing an ED50 value of 26 mg/kg in the rat-MES test and a remarkable PI (PI = TD50/ED50) value above 19. The better anticonvulsant potency of compound 21 and its wider safety margin compared to valproic acid (VPA) and zonisamide make it a potential candidate to become a new AED second-generation to VPA.

KW - 2,2,3,3-Tetramethylcyclopropanecarboxylic acid

KW - Anticonvulsants

KW - Maximal electroshock seizure test

KW - Phenyl-alkyl-amines

KW - Structure-activity relationships

KW - Subcutaneous pentylenetetrazole seizure test

KW - Sulfonamides

KW - Valproic acid

UR - https://www.scopus.com/pages/publications/44449083297

U2 - 10.1016/j.bmc.2008.03.051

DO - 10.1016/j.bmc.2008.03.051

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 18472270

AN - SCOPUS:44449083297

SN - 0968-0896

VL - 16

SP - 6297

EP - 6305

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

IS - 11

ER -

Synthesis and anticonvulsant activity of aromatic tetramethylcyclopropanecarboxamide derivatives

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this