Potential Anticonvulsant Agents Research Articles

Study, Docking, in silico ADME and Predicted Acute Toxicity of Novel Hetero-Aromatic Imidazolidine Analogues as Potential Anti-Epileptic Agents

Study, Docking, in silico ADME and Predicted Acute Toxicity of Novel Hetero-Aromatic Imidazolidine Analogues as Potential Anti-Epileptic Agents

Design, synthesis, molecular docking and pharmacological evaluation of some thiadiazole based nipecotic acid derivatives as a potential anticonvulsant and antidepressant agents

Design, synthesis, molecular docking and pharmacological evaluation of some thiadiazole based nipecotic acid derivatives as a potential anticonvulsant and antidepressant agents

Synthesis, molecular docking, electrochemical and fluorimetric analysis of new caffeic and cinnamic acid-conjugated hemorphin derivatives designed as potential anticonvulsant and antinociceptive agents

Based on the pharmacophore model of opioid receptors, our team recently synthesized a series of short‐chain hemorphin peptide analogs containing non‐natural amino acids. They demonstrated anticonvulsant and antinociceptive activity with low neurotoxicity. In the present study, a series of novel bioconjugates of N-modified hemorphin analogs containing second pharmacophore cinnamic acids (CA) or caffeic (KA) were synthesized by a traditional solid-phase Fmoc chemistry method for peptide synthesis. Electrochemical and fluorimetric analysis, in vivo anticonvulsant and antinociceptive activity in mice were conducted on the compounds. The three CA acid- (H4-CA, H5-CA, and H7-CA) and three KA acid- (H4-KA, H5-KA, and H7-KA) conjugated hemorphin derivatives exhibited potency at the highest doses of 2 µg/5 µl, administered by intracerebroventricular (icv) mode, against seizure spread in the maximal electroshock test (MES) in mice. The KA-conjugated H5-KA derivate, at the lowest dose, was the only compound that suppressed clonic seizures in the subcutaneous pentylenetetrazol (scPTZ) test. Except for the H5-CA, all tested CA acid- and KA acid-conjugated peptide derivates had the potency to increase the latency for clonic seizures in a dose-dependent mode. The activity against the psychomotor seizures in the 6-Hz test was detected only for the H4-CA (0.5 µg) and H4-KA (0.5 µg and 1 µg), respectively. All investigated peptides showed a more pronounced antinociceptive effect in the “intraplantar formalin” test compared to the “hot plate” test. Shorter chain analogs showed a better antinociceptive profile against tonic pain. The data suggest a DOR and KOR-mediated mechanism of action. According to the docking analysis, H7-CA showed a different antinociceptive profile than other investigated peptides. The novel peptide derivates did not exhibit neurotoxicity in the rotarod test. Our findings suggest that conjugated CA and KA morphine peptides can be used to develop novel morphine-related analogs with anticonvulsant and antinociceptive activity.

Advancement in Epilepsy Pharmacotherapy: An Insight into the Pharmacophoric Approaches of Recent Drugs.

Epilepsy is the most general, extensive, and severe neurological disorder, affecting more than 50 million individuals globally. Initially, conventional medicines and simple salts like potassium bromide were employed as antiepileptic medication candidates. Nowadays, many anticonvulsant drugs have been discovered as first-generation and second-generation and newer drugs and are still in development phases. The pharmacophore-based drug design process includes pharmacophore modeling and validation, pharmacophore-based virtual screening, virtual hits profiling, and lead identification with special reference. This comprehensive article reviews recently developed anticonvulsant derivatives on the basis of pharmacophoric approaches. A literature survey was performed using various search engines like Google Scholar, Scopus, Sci Finder, ScienceDirect, Science gate, Scilit, PubMed, NINDS database of NIH, Bentham Sciences, and other online and print journals and scientific databases. The presented review discusses such kinds of newer drugs that are in the market as well as in clinical trial phases. Detailed outcomes of pharmacophoric modeling have been discussed for newly derived derivatives like targets involved in Epilepsy, lead molecules etc., for the treatment of epilepsy. This exhaustive review will assist the researchers in the further development of potential antiepileptic agents.

Study, Docking, In Silico ADME and Bio-Evaluation of Novel Hetero-Aromatic Amino Acid Derivatives as Potential Anti-Epileptic Agents

Study, Docking, In Silico ADME and Bio-Evaluation of Novel Hetero-Aromatic Amino Acid Derivatives as Potential Anti-Epileptic Agents

Hybridization of the effective pharmacophores for treatment of epilepsy: design, synthesis, in vivo anticonvulsant activity, and in silico studies of phenoxyphenyl-1,3,4-oxadiazole-thio-N-phenylacetamid hybrids

BackgroundEpilepsy is a common neurological disorder. The available drugs for this disease only control convulsions in nearly 70% of patients, while bearing many side effects. In this study, a new series of phenoxyphenyl-1,3,4-oxadiazole-thio-N-phenylacetamid hybrids 8a-m was designed, synthesized, and evaluated as potent anticonvulsant agents.MethodsPhenoxyphenyl-1,3,4-oxadiazole-thio-N-phenylacetamid derivatives 8a-m were synthesized with well-known chemical reactions and anticonvulsant activity of them was determined by pentylenetetrazole (PTZ) and maximal electroshock (MES) induced seizures in mice. Phenoxyphenyl-1,3,4-oxadiazole-thio-N-phenylacetamid scaffold has the necessary pharmacophores to be a benzodiazepine (BZD) receptor agonist, thus, the most potent anticonvulsant compounds were assayed in vivo and in silico as BZD receptor agonist. Furthermore, in vivo neurotoxicity evaluation and in silico physicochemical, pharmacokinetic, and toxicity study on the most potent compounds were also performed.ResultsObtained results demonstrated that two compounds among the title new compounds have anticonvulsant activity in PTZ test while all of the new compounds are active in the MES test. The best anticonvulsant activities were obtained with nitro derivatives 8k and 8L. In vivo evaluation of flumazenil effect (a BZD receptor antagonist) on anticonvulsant activity of compound 8k confirmed that this compound is a BZD receptor agonist. The most potent compounds 8k and 8L interacted with the important residues of BZD-binding site of GABAA receptor. Furthermore, neurotoxicity of the latter compounds was lower than positive control diazepam.ConclusionAccording to these results, our designed scaffold can be a valuable lead structure for further structural developments and assessments to obtain a new potent anticonvulsant agent.

Vibrational spectral and electronic properties, Topology studies and biological assay of a potent Anticonvulsant agent: Divalproex Sodium

In this research work, Density Functional Theory based computational analysis on the molecular structure of Divalproex Sodium was carried out in the gas phase. Comprehensive analysis of vibrational spectra, Proton and Carbon Nuclear Magnetic Resonance, and electronic absorption spectrum have been carried out and the findings were compared to those obtained using computational techniques. The electronic transport properties were studied by the Ultraviolet-Visible spectrum obtained in distinct solvents by Time Dependent-Density Functional Theory method. Also, inter and intra-molecular interactions and charge transfer activity within the system were studied by Natural Bond Orbital and Frontier Molecular Orbital analyses. For the Non-Linear Optical profile of the compound, hyperpolarizability calculations were performed. The chemical reactivity of the investigated substance has also been disclosed by reactivity descriptors. The biological assessment through drug-likeness characteristics and molecular docking studies was performed to find the compound as anticonvulsant drugs. Highlights Optimized geometrical parameters were computed Vibrational, Electronic, and NMR spectra have been analyzed. Stability and chemical reactivity were studied. Inter/intramolecular interactions have been observed. Pharmacological activities were reported.

K+ Channels and Some Familiar Antiepileptic Drugs: Evaluation of Their the Structure-Activity Relationships with Molecular Docking Analysis

This study includes the structure-activity relationship of active molecules that are commonly used in the treatment of convulsive seizures in epileptic diseases. Well-known epileptic active molecules studied are: Vigabatrin, Lokosamidine, Zonisamide, Oxcarbazepine, Levetiresetam, Tiagabine, Topiramate, Lamotrigin, Gabapentin, Felbamat, Ethosuximide, Valproic Acid, Mesuximide, Ethotoin, Primidon, Trimethadion, Phenytoin, Remasemide, Mephenytoin. These molecules, which were selected considering the physiopathological mechanisms of action of epileptic disease, were considered suitable for molecular docking studies since they were used as a potential antiepileptic agent. In addition, it was focused on the potassium channels, which were prominent in the mechanisms of epilepsy. During the action potential that triggers seizure formation, inward rectifying potassium channels (KIR3.2) make a important role providing the flow of K+ ions. 
 Thus, PDB ID: 4KFM receptor was chosen for molecular docking study, since its act as an agonist according to its activity on the canal in the case of epileptic seizures formation. The result of molecular docking analysis demonstrated that Phenytoin gave the best binding affinity for 4KFM with a value of -6.2 kcal/mol. Other analysis in descending order (as kcal/mol); Oxcarbazepine (-6,0), Remasemide (-5.9), Topiramate and Primidon (-5.8), Tiagabine, Felbamat and Mesuximide (-5.7), Lamotrigin (-5.6) Zonisamide, Ethotoin and Mephenytoin, Lokosamidine (-5.5), Gabapentin (-4.8), Trimethadion (-4.7), Ethosuximide (-4.6), Levetiresetam (-4.5), Vigabatrin (-4.0), Valproic Acid (-3.9) determined as.

Discovery of Novel Isonipecotic Acid-Based Heteroaryl Amino Acid Derivatives as Potential Anticonvulsant Agents: Design, Synthesis, In-Silico ADME Study, and Molecular Docking Studies.

Epilepsy is a neurological disorder characterized by anomalous brain activity, convulsions, and odd behavior. Several substituted-(naphthalen-2-yl)-3-(1H-indol-3-yl) allyl)-1,4-dihydropyridine-4-carboxylic acid derivatives (5a-j) were intended to be produced in the current research effort to reduce convulsions and seizures. The newly developed compounds were produced by the prescribed process. Numerous methods (infrared spectroscopy (IR), nuclear magnetic resonance (NMR), mass, elemental analysis, etc.) were used to characterize these substances. Several models were used to test each of these molecules for anticonvulsant activity. By using the rotarod and ethanol potentiation techniques, neurotoxicity was also evaluated. The study meticulously examined each parameter and showed absorption, distribution, metabolism, and excretion (ADME) predictions for each of the 10 congeners that were produced. In addition, studies on molecular docking employed the gamma amino butyric acid (GABA)-A target protein. Anticonvulsant screening results identified compounds 5f, 5h, 5d, and 5b as the most efficacious of the series. All synthesized equivalents largely passed the neurotoxicity test. The results of molecular docking revealed significant interactions at the active site of GABA-A with LEU B: 99, TYR A: 62, Ala A: 174, and THR B: 202, and the outcomes were good and in agreement with in vivo findings. The study's findings showed that some substances had promising anticonvulsant properties that were comparable to those of the standard drug. The highly active novel anticonvulsant analogs may therefore represent a possible lead, and additional studies may result in a potential new drug candidate.

Design, synthesis, molecular docking and pharmacological evaluation of novel triazine-based triazole derivatives as potential anticonvulsant agents

Triazine-linked triazole compounds (4a-j) were designed, synthesized, and then examined for their anticonvulsant abilities. Compounds 4e, 4f, 4g, 4i, and 4j displayed significant anticonvulsant activity in both maximum electroshock seizure (MES) and pentylenetetrazole (PTZ) induced seizure during the preliminary screening. The phase II anticonvulsant activity statistics revealed that compounds 4e, 4f, 4g, 4i, and 4j demonstrated excellent activity as compared to the conventional drugs methaqualone and valproate, supporting the potential of these triazine-linked triazole analogues as novel anticonvulsant agents. To take use of the findings, computational parameters including docking analysis and drug-likeness prediction were carried out. Molecular modelling studies supported the essential pharmacophoric information that the structure activity relationship offered. The triazine-linked triazole analogues that were investigated might be viewed as helpful models for future research and derivatization.

Neuroprotective and anti-epileptic potentials of genus Artemisia L.

The Genus Artemisia L. is one of the largest genera in the Asteraceae family growing wild over in Europe, North America, and Central Asia and has been widely used in folk medicine for the treatment of various ailments. Phytochemical and psychopharmacological studies indicated that the genus Artemisia extracts contain various antioxidant and anti-inflammatory compounds and possess antioxidant, anti-inflammatory, antimicrobial, antimalarial, and antitumor activity. Recently, increasing experimental studies demonstrated that many Artemisia extracts offer a great antiepileptic potential, which was attributed to their bioactive components via various mechanisms of action. However, detailed literature on the antiepileptic properties of the genus Artemisia and its mechanism of action is segregated. In this review, we tried to gather the detailed neuroprotective and antiepileptic properties of the genus Artemisia and its possible underlying mechanisms. In this respect, 63 articles were identified in the PubMed and Google scholars databases, from which 18 studies were examined based on the pharmacological use of the genus Artemisia species in epilepsy. The genus Artemisia extracts have been reported to possess antioxidant, anti-inflammatory, neurotransmitter-modulating, anti-apoptotic, anticonvulsant, and pro-cognitive properties by modulating oxidative stress caused by mitochondrial ROS production and an imbalance of antioxidant enzymes, by protecting mitochondrial membrane potential required for ATP production, by upregulating GABA-A receptor and nACh receptor activities, and by interfering with various anti-inflammatory and anti-apoptotic signaling pathways, such as mitochondrial apoptosis pathway, ERK/CREB/Bcl-2 pathway and Nrf2 pathway. This review provides detailed information about some species of the genus Artemisia as potential antiepileptic agents. Hence, we recommend further investigations on the purification and identification of the most biological effective compounds of Artemisia and the mechanisms of their action to cure epilepsy and other neurological diseases.

Novel spiro[indene-1,2'-quinazolin]-4'(3'H)-one derivatives as potent anticonvulsant agents: One-pot synthesis, in vivo biological evaluation, and molecular docking studies.

A new series of spiro[indene-1,2'-quinazolin]-4'(3'H)-one derivatives 4a-m were synthesized via a one-pot method and evaluated for anticonvulsant activities using pentylenetetrazole (PTZ) and maximal electroshock (MES)-induced seizures. Obtained results demonstrated that these compounds have not anticonvulsant activity in PTZ test while are active in the MES test. Among the synthesized compounds, the best anticonvulsant activity was obtained with compound 4h. This compound also was not neurotoxic. Given that the title new compounds have the pharmacophore requirement for benzodiazepine (BZD) receptor agonist, the most potent compound was assayed in vivo and in silico as BZD receptor agonist. After treatment with flumazenil as a standard BZD receptor antagonist, anticonvulsant activity of compound 4h decreased. Therefore, the involvement of BZD receptors in anticonvulsant activity of this compound confirmed. Furthermore, docking study of compound 4h in the BZD-binding site of GABAA receptor confirmed that this compound interacted with the important residues.

Investigation Of Structure-Activity Relationships With Molecular Docking For Some Antiepileptic Drugs And Voltage-Gated Calcium (CaV) Channels

In the study, the active drugs molecules used in the treatment of convulsive seizures occurring in epilepsy disease were used. These molecules; Vigabatrin, Lokosamidin, Zonisamide, Oxcarbazepine, Levetiracetam, Tiagabin, Topiramate, Lamotrigine, Gabapentin, Felbamate, Ethosuximide, Valproic Acid, Mesuximide, Ethotoin, Primidone, Trimethadion, Phenytoin, Remasemide, Mephenytoin. These molecules have been selected considering the physiopathological mechanisms of action of epilepsy. Since the selected molecules are used as a potential antiepileptic agent, they were deemed suitable for molecular insertion studies. In addition, voltage-gated calcium channels, which play an important role in epilepsy, are emphasized. Voltage-gated calcium channels (CaV) act by providing the flow of Ca+ ions during the action potential that triggers seizure formation, and among the ten subtypes of voltage-gated calcium (CaV) channels, CaV3.1- CaV3.3, T-type or abnormal activities are associated with epilepsy, psychiatric form the associated low-voltage-activated subfamily. For this reason, the PDB ID: 6KZP receptor, which acts as an antagonist according to its activity on the channel in the formation of epileptic seizures, was chosen for the molecular insertion study. As a result of molecular placement studies; Oxcarbazepine and Phenytoin gave the best binding affinity for 6KZP with a value of -7.5 kcal/mol. Other results are in descending order (in kcal/mol); Tiagabine (-7.4), Mesuximide (-7.3), Primidone (-7.1), Remasemide (-7.0), Topiramate (-6.9) Mephenytoin (-6.7), Lomotrigine and Ethotoin (-6.4), Locosamide and Zonisamide (-6.1) , Felbamate (-6.0), Levetiracetam and Gabapentin (-5.4), Esuximide (-5.1), Valproic Acid (-4.9), Trimethadione (-4.7), Vigabatrin (-4.4) determined as.

Pyrrolopyridine and Isoindole as Potential Anticonvulsant Agents: Design, Synthesis, and Pharmacological Evaluation.

Phthalimide, as the rigid form of ameltolide, exhibits a phenytoin-like profile of drug-receptor interaction and is active in the MES model and inactive in the PTZ model as an anti-epileptic agent. In this research, based on the isosteric replacement, we reported the design, preparation, and antiepileptic activity of 13 new analogs of pyrrolopyridine and isoindole. The designed compounds were prepared by condensing 3, 4-pyridine dicarboxylic anhydride, or 4-fluorophthalic anhydride with different aryl amines. MES and PTZ-induced seizure models were utilized to evaluate the antiepileptic effect of the prepared ligands. It was found that the prepared ligands have significantly affected both tonic and clonic seizures. In tonic seizures, the prepared compounds decreased mortality to a significant extent, and in clonic seizures, they significantly showed better frequency and latency. Compounds 9, 12, and 13 were the most potent ligands than phenytoin. It is concluded that the best distance between two aryl parts is two bonds, and the substitution of the nitro group at the meta position of the phenyl ring is better than the para position. Our research group has investigated this concept for designing newer compounds with better anticonvulsant activity.

Synthetic and natural coumarins as potent anticonvulsant agents: A review with structure-activity relationship.

The main objective of this review is to highlight the most relevant studies since 1990 (to date) in the area of medicinal chemistry aspects to provide a panoramic view to the biologists/medicinal chemists working in this area and would assist them in their efforts to design, synthesize and extract (from natural source) coumarin-based anticonvulsant agents. Also, the structure-activity relationship (SAR) studies are also discussed for further rational design of this kind of derivatives. It is hoped that this review will be helpful for new thoughts in the quest for rational designs of more active and less toxic coumarin-based antiepileptic agents. A literature review emphasizing the application of coumarin core as antiepileptic agents identify articles related to the topic; we performed a standardized search from 1990 to November 2021, using search engines like Scifinder, web of Science, Pubmed and Scopus. This review gives an overview of attempts to shed light and compile published reports on coumarin derivatives along with some opinions on different approaches to help the medicinal chemists in designing future generation potent yet safer anticonvulsant agents. The possible structure-activity relationships (SARs) will also be discussed to indicate the direction for the rational design of more effective candidates. The findings from this review provide new indications or directions for the discovery of new and better drugs from synthetic and naturally occurring coumarins as antiepileptic agents. In our review, we have tried to depict the recent researches which made in the design and development of novel anticonvulsant compounds with coumarin nucleus. Also, SAR of expressed derivatives indicated that the choice of a fitting substitution containing electron-withdrawing/donating groups to coumarin or with some heterocyclic moieties joined to parent coumarin skeleton assumes an essential role in changing the anticonvulsant activity of synthesized derivatives. These findings encourage the scientific community towards the optimization of the pharmacological profile of this structural moiety as an important scaffold for the treatment of epilepsy.

Synthesis and Biological Activity Evaluation of Some New Coumarin Derivatives as Potent Anticonvulsant and CNS-Depressant Agents

Triazolo-thiadiazines 4a–f and triazolo-tetrazines 8g–l were prepared from reaction of 3-(4-amino-5-mercapto-4H-1,2,4-triazol-3-yl)-2H-chromen-2-one with the respective hydrazonoyl halides 2a–f and 2g–l. Moreover, the reaction of the aminomercaptotriazole derivative with phenacyl bromide and ethyl 2-chloro-3-oxobutanoate followed by the coupling reaction of the products with benzenediazonium chloride yielded the corresponding products 4f and 8g, respectively. All of the newly prepared heterocyclic derivatives were determined using spectral data, elemental analysis, and alternate methods. The in-vivo anticonvulsant and CNS-depressant activities of all the prepared derivatives were tested using the maximal electroshock method and showed excellent activities, especially triazolo[4,3-b]tetrazine derivatives 8j, 8k, and 8l. Additionally, their structure–activity relationship was proven clearly, demonstrating that electron-releasing groups increase activities while electron-withdrawing groups lower them.

Ultrasonic Assisted Synthesis, Biological Evaluation, and Molecular Docking of Chalcone-based 1,5-benzodiazepine as Potential Anticonvulsant Agents

Background:Epilepsy is a constant neurological disorder influencing around 50 million individuals globally. However, most epileptic patients do not react to accessible medications and clinical treatments. This research work has been planned to produce novel 1,5-benzodiazepines from chalcone intermediates by ultrasonic irradiation method and perform the anticonvulsant activity by pentylenetetrazole incited seizures tests.Method:Chalcones are used as precursors for synthesizing 1, 5-benzodiazepines by a reaction with ophenylenediamine in absolute ethanol in the presence of glacial acetic acid as a catalyst. The proposed synthesized structures were characterized by melting point, TLC, FTIR, 1H & 13CNMR, and mass spectroscopy. All the molecules were assessed for anticonvulsant activity.Result:Anticonvulsant activity uncovered the fact that the mixes derived from dimethylamino, dimethoxy, hydroxy-substituted chalcones in the 1, 5-benzodiazepines can be used for seizures in mice. These pharmacological examinations have shown that these new subsidiaries can repress seizures incited by pentylenetetrazole in mice proficiently. Our molecular docking studies also supported probable effects.Conclusion:The results are promising, which on further assessments may provoke medicine particles against seizures in mice.

Design, synthesis and evaluation of piperazine clubbed 1,2,4-triazine derivatives as potent anticonvulsant agents

The new series of N-(5,6-diphenyl-1,2,4-triazin-3-yl)-2-(4-substituted piperazin-1-yl) acetamide (RP1–5) and 2-((5,6-diphenyl-1,2,4-triazin-3-yl)thio)-1-(4- substituted piperazin-1-yl)-ethan-1-one (RP6–10) derivatives were designed and synthesised by clubbing substituted 5,6-diphenyl-1,2,4-triazine with different substituted piperazines. The synthesized compounds were tested for anticonvulsant activity and various biochemical toxicity parameters. Among the series, two compounds (2-(4-benzylpiperazin-1-yl)-N-(5,6-diphenyl-1,2,4-triazin-3-yl)acetamide (RP4), and 2‑chloro-1-(4-substituted piperazin-1-yl)ethan-1-one (RP5) were found to demonstrate the most potent anticonvulsant activity in both MES and scPTZ convulsion mice models. The most active compound RP5 was effective at median doses (ED50) of 14.82 mg/kg in MES and 14.61 mg/kg in scPTZ model. The median toxic dose (TD50) was > 600 which provided the compound RP5 with high protective index of 40.48 in the MES test and 41.06 in scPTZ test. Further, both the compounds were also found to possess significant antidepressant activity. The compounds did not show any adverse effect in various parameters such as grip-strength test (skeletal muscular strength), actophotometer, and rotarod test (locomotor) as compared to the control groups. In biochemical estimation, RP4 and RP5 were found nontoxic and showed no sign of any pathological changes in blood chemistry, liver, and nephrology of the kidney. The GABA level estimation in the whole brain of mice was performed to predict the mechanistic study of the selected compounds.

Development and Validation of Stability-Indicating Assay Method for a Novel Oxazolidinone (PH-192) with Anticonvulsant Activity by Using UHPLC-QToF-MS.

The treatment of seizure disorders with currently available pharmacotherapeutic agents is not optimal due to the failure of some patients to respond, coupled with occurrences of side effects. There is therefore a need for research into the development of new chemical entities as potential anticonvulsant agents, which are different structurally from the existing class of drugs. We recently identified a novel triazolyl-oxazolidinone derivative, PH-192, as a potential anticonvulsant agent. PH-192 demonstrated protection comparable to phenytoin against both chemically- and electrically-induced seizures in rodents with little or no central nervous system side effects. However, PH-192 did not exhibit protection beyond 30 min; therefore, we decide to investigate a stability-indicating assay of PH-192 in plasma and other solutions. A reliable and validated analytical method was developed to investigate the stability of PH-192 for 90 min in human plasma, acidic, basic, and oxidative conditions, using a Waters Acquity ultra high-performance liquid chromatography (UHPLC) system with a quaternary Solvent Manager (H-Class). A simple extraction method indicated that PH-192 was stable in human plasma after 90 min at 37 °C, with more than 90% successfully recovered. Moreover, stress stability studies were performed, and degradants were identified using LC-QToF-MS under acidic, basic, and oxidative simulated conditions.

Synthesis and Biological Evaluation of Some Newer 1h-Benzo[b][1,5]diazepin-2(3h)-One Derivatives as Potential Anticonvulsant Agents

Background: Regardless of the availability of all novel and earlier treatments, seizure control is notoriously complicated. In the hopes of discovering the latest and ultimate therapy, medicinal chemists will keep on to hunt for new antiepileptic compounds with high specificity and low CNS toxicity. The biological effects of benzodiazepine compounds have been examined. Benzene and a diazepine ring are fused together to form the chemical structure. Diverse combinations of moieties attached to the innermost structure in positions 1, 2, 5, and 7 the pharmacological qualities, effect potency, and pharmacokinetic conditions are all influenced by the various side groups. Method: This paper describes the synthesis of several 1H-benzo[b][1,5]diazepin-2(3H)-one derivatives. The substituents at N1 are benzoyl, 5-substituted-1,3,4-thiadiazoles-2-yl-aminoacetyl. Condensation of orthophenylene diamine with ethyl acetoacetate gave 7-substituted-4-methyl-1H-benzo[b][1,5]diazepin-2(3H)-ones, which were then linked to benzoyl chloride and chloroacetyl chloride to yield N1-benzoyl and N1-chloroacetyl derivatives. N1- chloroacetyl derivatives were further linked with 5-substituted-1,3,4-thiadiazoles amines using microwave irradiation. Result: IR, 1H-NMR, and mass spectroscopy were used to authenticate the synthesized compounds. The PTZ produced convulsions method was used to test the compounds for anticonvulsant activity. Compounds 4a and 4c gave 80% protection at 0.4 mg/kg, whereas Compounds 2a and 2c offered 80% protection at 20 and 30 mg/kg, respectively, when compared to the Control. Conclusion: When compared to a control, the experimental synthesis and pharmacological assessment of the 1,5-benzodiazepin-2-one moiety replaced with 1,3,4-thiadiazole yields a potentially active anticonvulsant drug.