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

Abstract

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.

Diverse Biological Activities of 1,3,4-Thiadiazole Scaffold

“…They confirmed the structure using analytical spectroscopy and further screened the compounds for in-vitro anti-convulsant activity on Swiss albino mice. Compounds 5 and 6 were found to be highly potent, while compound 7 displayed moderate anti-convulsant activity [33]. Aliyu A et al (2021) also designed and synthesized a new thiadiazole derivative by condensation reaction and evaluated it for in-vitro anti-convulsant activity on mice by PTZ and MES method and found 8 to be a potent compound with no toxicity [34] (Figure 2).…”

Thiadiazole/Thiadiazine Derivatives as Insecticidal Agent: Design, Synthesis, and Biological Assessment of 1,3,4-(Thiadiazine/Thiadiazole)-Benzenesulfonamide Derivatives as IGRs Analogues against Spodoptera littoralis

“…1,3,4-thiadiazole is becoming increasingly important in medicinal chemistry. These agents include those that are anticonvulsant, 13 anti-Alzheimer, 14 anticancer and antitumor, 15 antidiabetic, 16 antiviral, 17 antiplatelet, 18 antituberculosis, 19 carbonic anhydrase inhibitor agents, 20 and diuretic agents. 21 Insecticidal, 22 herbicidal, 23 antifungal, 24 and plant growth regulating compounds 25 are among the pesticides that have been studied.…”

“…The synthesis of insecticidal drugs has focused a great deal of research on tiny compounds containing a heterocyclic moiety with five or six members, specially 1,3,4-thiadiazole and 1,3,4-thiadiazine. − Because of its physiological activity, 1,3,4-thiadiazole is becoming increasingly important in medicinal chemistry. These agents include those that are anticonvulsant, anti-Alzheimer, anticancer and antitumor, antidiabetic, antiviral, antiplatelet, antituberculosis, carbonic anhydrase inhibitor agents, and diuretic agents . Insecticidal, herbicidal, antifungal, and plant growth regulating compounds are among the pesticides that have been studied.…”