Anticonvulsant Profiles of Certain New 6-Aryl-9-substituted-6,9-diazaspiro-[4.5]decane-8,10-diones and 1-Aryl-4-substituted-1,4-diazaspiro[5.5]undecane-3,5-diones
Synthesis and anticonvulsant potential of certain new 6-aryl-9-substituted-6,9-diazaspiro[4.5]decane-8,10-diones (6a–l) and 1-aryl-4-substituted-1,4-diazaspiro[5.5] undecane-3,5-diones (6m–x) are reported. The intermediates 1-[(aryl)(cyanomethyl)amino] cycloalkanecarboxamides (3a–f) were prepared vi...
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doaj-c977f7f3c26845549ebee7dea07ee5652020-11-25T01:36:25ZengMDPI AGInternational Journal of Molecular Sciences1422-00672014-09-01159169111693510.3390/ijms150916911ijms150916911Anticonvulsant Profiles of Certain New 6-Aryl-9-substituted-6,9-diazaspiro-[4.5]decane-8,10-diones and 1-Aryl-4-substituted-1,4-diazaspiro[5.5]undecane-3,5-dionesMohamed N. Aboul-Enein0Aida A. El-Azzouny1Mohamed I. Attia2Yousreya A. Maklad3Mona E. Aboutabl4Fatma Ragab5Walaa H. A. Abd El-Hamid6Medicinal and Pharmaceutical Chemistry Department (Medicinal Chemistry Group), Pharmaceutical and Drug Industries Research Division, National Research Centre, Dokki, Giza 12622, EgyptMedicinal and Pharmaceutical Chemistry Department (Medicinal Chemistry Group), Pharmaceutical and Drug Industries Research Division, National Research Centre, Dokki, Giza 12622, EgyptMedicinal and Pharmaceutical Chemistry Department (Medicinal Chemistry Group), Pharmaceutical and Drug Industries Research Division, National Research Centre, Dokki, Giza 12622, EgyptMedicinal and Pharmaceutical Chemistry Department (Pharmacology Group) Pharmaceutical and Drug Industries Research Division, National Research Centre, Dokki, Giza 12622, EgyptMedicinal and Pharmaceutical Chemistry Department (Pharmacology Group) Pharmaceutical and Drug Industries Research Division, National Research Centre, Dokki, Giza 12622, EgyptDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Cairo 11562, EgyptDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Misr University for Science & Technology, 6th of October City 12566, EgyptSynthesis and anticonvulsant potential of certain new 6-aryl-9-substituted-6,9-diazaspiro[4.5]decane-8,10-diones (6a–l) and 1-aryl-4-substituted-1,4-diazaspiro[5.5] undecane-3,5-diones (6m–x) are reported. The intermediates 1-[(aryl)(cyanomethyl)amino] cycloalkanecarboxamides (3a–f) were prepared via adopting Strecker synthesis on the proper cycloalkanone followed by partial hydrolysis of the obtained nitrile functionality and subsequent N-cyanomethylation. Compounds 3a–f were subjected to complete nitrile hydrolysis to give the respective carboxylic acid derivatives 4a–f which were cyclized under mild conditions to give the spiro compounds 5a–f. Ultimately, compounds 5a–f were alkylated or aralkylated to give the target compounds 6a–i and 6m–u. On the other hand, compounds 6j–l and 6v–x were synthesized from the intermediates 5a–f through alkylation, dehydration and finally tetrazole ring formation. Anticonvulsant screening of the target compounds 6a–x revealed that compound 6g showed an ED50 of 0.0043 mmol/kg in the scPTZ screen, being about 14 and 214 fold more potent than the reference drugs, Phenobarbital (ED50 = 0.06 mmol/kg) and Ethosuximide (ED50 = 0.92 mmol/kg), respectively. Compound 6e exhibited an ED50 of 0.019 mmol/kg, being about 1.8 fold more potent than that of the reference drug, Diphenylhydantoin (ED50 = 0.034 mmol/kg) in the MES screen. Interestingly, all the test compounds 6a–x did not show any minimal motor impairment at the maximum administered dose in the neurotoxicity screen.http://www.mdpi.com/1422-0067/15/9/16911cycloalkanonesStrecker synthesisalkylationspiro compoundstetrazoleanticonvulsant |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mohamed N. Aboul-Enein Aida A. El-Azzouny Mohamed I. Attia Yousreya A. Maklad Mona E. Aboutabl Fatma Ragab Walaa H. A. Abd El-Hamid |
spellingShingle |
Mohamed N. Aboul-Enein Aida A. El-Azzouny Mohamed I. Attia Yousreya A. Maklad Mona E. Aboutabl Fatma Ragab Walaa H. A. Abd El-Hamid Anticonvulsant Profiles of Certain New 6-Aryl-9-substituted-6,9-diazaspiro-[4.5]decane-8,10-diones and 1-Aryl-4-substituted-1,4-diazaspiro[5.5]undecane-3,5-diones International Journal of Molecular Sciences cycloalkanones Strecker synthesis alkylation spiro compounds tetrazole anticonvulsant |
author_facet |
Mohamed N. Aboul-Enein Aida A. El-Azzouny Mohamed I. Attia Yousreya A. Maklad Mona E. Aboutabl Fatma Ragab Walaa H. A. Abd El-Hamid |
author_sort |
Mohamed N. Aboul-Enein |
title |
Anticonvulsant Profiles of Certain New 6-Aryl-9-substituted-6,9-diazaspiro-[4.5]decane-8,10-diones and 1-Aryl-4-substituted-1,4-diazaspiro[5.5]undecane-3,5-diones |
title_short |
Anticonvulsant Profiles of Certain New 6-Aryl-9-substituted-6,9-diazaspiro-[4.5]decane-8,10-diones and 1-Aryl-4-substituted-1,4-diazaspiro[5.5]undecane-3,5-diones |
title_full |
Anticonvulsant Profiles of Certain New 6-Aryl-9-substituted-6,9-diazaspiro-[4.5]decane-8,10-diones and 1-Aryl-4-substituted-1,4-diazaspiro[5.5]undecane-3,5-diones |
title_fullStr |
Anticonvulsant Profiles of Certain New 6-Aryl-9-substituted-6,9-diazaspiro-[4.5]decane-8,10-diones and 1-Aryl-4-substituted-1,4-diazaspiro[5.5]undecane-3,5-diones |
title_full_unstemmed |
Anticonvulsant Profiles of Certain New 6-Aryl-9-substituted-6,9-diazaspiro-[4.5]decane-8,10-diones and 1-Aryl-4-substituted-1,4-diazaspiro[5.5]undecane-3,5-diones |
title_sort |
anticonvulsant profiles of certain new 6-aryl-9-substituted-6,9-diazaspiro-[4.5]decane-8,10-diones and 1-aryl-4-substituted-1,4-diazaspiro[5.5]undecane-3,5-diones |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2014-09-01 |
description |
Synthesis and anticonvulsant potential of certain new 6-aryl-9-substituted-6,9-diazaspiro[4.5]decane-8,10-diones (6a–l) and 1-aryl-4-substituted-1,4-diazaspiro[5.5] undecane-3,5-diones (6m–x) are reported. The intermediates 1-[(aryl)(cyanomethyl)amino] cycloalkanecarboxamides (3a–f) were prepared via adopting Strecker synthesis on the proper cycloalkanone followed by partial hydrolysis of the obtained nitrile functionality and subsequent N-cyanomethylation. Compounds 3a–f were subjected to complete nitrile hydrolysis to give the respective carboxylic acid derivatives 4a–f which were cyclized under mild conditions to give the spiro compounds 5a–f. Ultimately, compounds 5a–f were alkylated or aralkylated to give the target compounds 6a–i and 6m–u. On the other hand, compounds 6j–l and 6v–x were synthesized from the intermediates 5a–f through alkylation, dehydration and finally tetrazole ring formation. Anticonvulsant screening of the target compounds 6a–x revealed that compound 6g showed an ED50 of 0.0043 mmol/kg in the scPTZ screen, being about 14 and 214 fold more potent than the reference drugs, Phenobarbital (ED50 = 0.06 mmol/kg) and Ethosuximide (ED50 = 0.92 mmol/kg), respectively. Compound 6e exhibited an ED50 of 0.019 mmol/kg, being about 1.8 fold more potent than that of the reference drug, Diphenylhydantoin (ED50 = 0.034 mmol/kg) in the MES screen. Interestingly, all the test compounds 6a–x did not show any minimal motor impairment at the maximum administered dose in the neurotoxicity screen. |
topic |
cycloalkanones Strecker synthesis alkylation spiro compounds tetrazole anticonvulsant |
url |
http://www.mdpi.com/1422-0067/15/9/16911 |
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