ChemInform Abstract: Synthesis and Anticonvulsant Activity of N‐(2‐Hydroxyethyl)amide Derivatives.

Guan, Liping; Zhao, Donghai; Xiu, Jing-Hui; Sui, Xin; Piao, Hu‐Ri; Quan, Zhe‐Shan

doi:10.1002/chin.200919201

Cited by 2 publications

(3 citation statements)

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“…Scheme describes the synthesis of 18 F-FHEA ( 4 ). To synthesize the labeling precursor for 18 F-FHEA, 16-bromohexadecanoic acid was activated using methyl chloroformate and then reacted with ethanolamine in the presence of triethylamine to get N -(16-bromohexadecanoyl)ethanolamine ( 1 ) . The obtained bromo- N -acylethanolamine 1 was treated with 3,4-dihydro-2 H -pyran in the presence of p -toluenesulfonic acid in dichloromethane to obtain 16-bromo- N -[2[(tetrahydro-2 H -pyran-2-yl)oxy]ethyl]hexadecanoylamide ( 2 ) as precursor for radiofluorination.…”

Section: Resultsmentioning

confidence: 99%

Synthesis and Preliminary Evaluation of N-(16-¹⁸F-Fluorohexadecanoyl)ethanolamine (¹⁸F-FHEA) as a PET Probe of N-Acylethanolamine Metabolism in Mouse Brain

Pandey

DeGrado

Qian

et al. 2014

ACS Chem. Neurosci.

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N-Acylethanolamines are lipid signaling molecules found throughout the plant and animal kingdoms. The best-known mammalian compound of this class is anandamide, N-arachidonoylethanolamine, one of the endogenous ligands of cannabinoid CB1 and CB2 receptors. Signaling by N-acylethanolamines is terminated by release of the ethanolamine moiety by hydrolyzing enzymes such as fatty acid amide hydrolase (FAAH) and N-acylethanolamine-hydrolyzing amidase (NAAA). Herein, we report the design and synthesis of N-(16-(18)F-fluorohexadecanoyl)ethanolamine ((18)F-FHEA) as a positron emission tomography (PET) probe for imaging the activity of N-acylethanolamine hydrolyzing enzymes in the brain. Following intravenous administration of (18)F-FHEA in Swiss Webster mice, (18)F-FHEA was extracted from blood by the brain and underwent hydrolysis at the amide bond and incorporation of the resultant (18)F-fluorofatty acid into complex lipid pools. Pretreatment of mice with the FAAH inhibitor URB-597 (1 mg/kg IP) resulted in significantly slower (18)F-FHEA incorporation into lipid pools, but overall (18)F concentrations in brain regions were not altered. Likewise, pretreatment with a NAAA inhibitor, (S)-N-(2-oxo-3-oxytanyl)biphenyl-4-carboxamide (30 mg/kg IV), did not significantly affect the uptake of (18)F-FHEA in the brain. Although evidence was found that (18)F-FHEA behaves as a substrate of FAAH in the brain, the lack of sensitivity of brain uptake kinetics to FAAH inhibition discourages its use as a metabolically trapped PET probe of N-acylethanolamine hydrolyzing enzyme activity.

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Section: Resultsmentioning

confidence: 99%

Synthesis and Preliminary Evaluation of N-(16-¹⁸F-Fluorohexadecanoyl)ethanolamine (¹⁸F-FHEA) as a PET Probe of N-Acylethanolamine Metabolism in Mouse Brain

Pandey

DeGrado

Qian

et al. 2014

ACS Chem. Neurosci.

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“…The relationship between chain length and activity fluctuated in the case of a substituted alkyl chain of eleven to twenty-one carbon atoms, where compounds 54b (-n-C 15 H 31 ) and 54c (-n-C 17 H 35 ) were the most active. What's more, compounds with an unsaturated alkyl chain of 17 to 21 carbon atoms showed similar activity, while a compound with an unsaturated alkyl chain of ten carbon atoms showed stronger activity [197,198].…”

Section: Amide Derivativesmentioning

confidence: 91%

“…Guan et al [197,198] published a new series of N-(2-hydroxyethyl)amide derivatives and tested their anticonvulsant activities. These molecules were designed by using various carboxylic acids to establish the effect of the length of the alkyl chain, unsaturation along the alkyl chain, and insertion of a phenyl ring or substituted phenyl ring in to the alkyl chain on the anticonvulsant activity.…”

Section: Amide Derivativesmentioning

confidence: 99%

Recent Progress in Anticonvulsant Drug Research: Strategies for Anticonvulsant Drug Development and Applications of Antiepileptic Drugs for Non-Epileptic Central Nervous System Disorders

Dalkara

Karakurt²

2012

CTMC

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Major advances in antiepileptic drug therapy have taken place since 1950s. In the first period, several antiepileptic drugs (AEDs) such as phenobarbital, diphenylhydantoin, ethosuximide, carbamazepine, benzodiazepines and valproic acid were introduced to epilepsy treatment. After 1990 many new generation drugs (lamotrigine, topiramate, gabapentine, pregabaline, felbamate, lacosamide, levetiracetam etc.) have been developed. These novel AEDs have offered some advantages such as fewer side effects, fewer drug-drug interactions, and better pharmacokinetic properties. But pharmacoresistance and therapeutic failure in 20-25% of the patients remain the main reasons to continue efforts to find safer and more efficacious drugs and ultimate a treatment for this devastating disease. Several AEDs especially novel compounds have been found to be effective also in the treatment of several other neurologic and psychiatric disorders. Chemical diversity of the newer antiepileptic drugs as well as those currently in clinical development is another point that encourages medicinal chemists to study this subject. This review summarizes recent studies on the development of potential anticonvulsant compounds in different chemical structures, their structure-activity relationships and also therapeutic usages of AEDs other than epilepsy.

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ChemInform Abstract: Synthesis and Anticonvulsant Activity of N‐(2‐Hydroxyethyl)amide Derivatives.

Cited by 2 publications

References 1 publication

Synthesis and Preliminary Evaluation of N-(16-¹⁸F-Fluorohexadecanoyl)ethanolamine (¹⁸F-FHEA) as a PET Probe of N-Acylethanolamine Metabolism in Mouse Brain

Synthesis and Preliminary Evaluation of N-(16-¹⁸F-Fluorohexadecanoyl)ethanolamine (¹⁸F-FHEA) as a PET Probe of N-Acylethanolamine Metabolism in Mouse Brain

Recent Progress in Anticonvulsant Drug Research: Strategies for Anticonvulsant Drug Development and Applications of Antiepileptic Drugs for Non-Epileptic Central Nervous System Disorders

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ChemInform Abstract: Synthesis and Anticonvulsant Activity of N‐(2‐Hydroxyethyl)amide Derivatives.

Cited by 2 publications

References 1 publication

Synthesis and Preliminary Evaluation of N-(16-18F-Fluorohexadecanoyl)ethanolamine (18F-FHEA) as a PET Probe of N-Acylethanolamine Metabolism in Mouse Brain

Synthesis and Preliminary Evaluation of N-(16-18F-Fluorohexadecanoyl)ethanolamine (18F-FHEA) as a PET Probe of N-Acylethanolamine Metabolism in Mouse Brain

Recent Progress in Anticonvulsant Drug Research: Strategies for Anticonvulsant Drug Development and Applications of Antiepileptic Drugs for Non-Epileptic Central Nervous System Disorders

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Synthesis and Preliminary Evaluation of N-(16-¹⁸F-Fluorohexadecanoyl)ethanolamine (¹⁸F-FHEA) as a PET Probe of N-Acylethanolamine Metabolism in Mouse Brain

Synthesis and Preliminary Evaluation of N-(16-¹⁸F-Fluorohexadecanoyl)ethanolamine (¹⁸F-FHEA) as a PET Probe of N-Acylethanolamine Metabolism in Mouse Brain