Design and Synthesis of 5‐Substituted Benzo[d][1,3]dioxole Derivatives as Potent Anticonvulsant Agents

Abstract

A series of 5-substituted benzo[d][1,3]dioxole derivatives was designed, synthesized, and tested for anticonvulsant activity using the maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) screens. Neurotoxicity was determined by rotarod test. In the preliminary screening, six compounds, 3a, 3c, 3d, and 4d-f, showed promising anticonvulsant activities in the MES model, and compounds 4c and 4d exhibited full protection against seizures at doses of 300 mg/kg in the scPTZ model. Among the synthesized compounds, 3c as the most active compound showed high protection against the MES-induced seizures with an ED value of 9.8 mg/kg and a TD value of 229.4 mg/kg after intraperitoneal injection into mice, thus providing compound 3c with a high protective index (TD /ED ) of 23.4 comparable to those of reference antiepileptic drugs.

In Vitro Anti‐Toxoplasma gondii Activity Evaluation of a New Series of Quinazolin‐4(3H)‐one Derivatives

“…The introduction of benzo[ d ]thiazole ( 8p ) and 1,2,3,4‐tetrahydronaphthalene ( 8q ) as R group at the side chain cannot either improve the activity or lower cytotoxicity, with similar IC 50 values and CC 50 values as compound 8a . Benzo[ d ][1,3]dioxole is a common scaffold in medicinal chemistry [22–23] and diaryl ether moiety is also usually represented in many molecules that own high efficacy in inhibiting T. gondii tachyzoites [24–26] . For this consideration, we synthesized three compounds to evaluate the effect of these two structures on the proliferation of T. gondii tachyzoites compared to 8a .…”

Synthesis of (E)‐3‐Alkylideneindolin‐2‐ones by an Iron‐Catalyzed Aerobic Oxidative Condensation of Csp3–H Bonds of Oxindoles and Benzylamines

“…In addition, ( E )‐3‐(benzo[ d ][1,3]dioxol‐5‐ylmethylene)indolin‐2‐one ( 4h ) and ( E )‐3‐(3,4,5‐trimethoxybenzylidene)‐5‐methoxyindolin‐2‐one ( 9 ) are identified as potent anticonvulsant agent and antitumor agent, respectively. [ 1c,17 ] Compound 9 could be synthesized by oxidative reaction of 5‐methoxyoxindole ( 7 ) with 3,4,5‐trimethoxybenzylamine ( 8 ) under the standard conditions (Scheme 4b). Besides, many of the synthesized 3‐alkylideneindolin‐2‐one compounds, namely ( E )‐3‐benzylidene‐7‐chloroindolin‐2‐one ( 3j ), ( E )‐3‐benzylidene‐5‐bromoindolin‐2‐one ( 3k ) and ( E )‐3‐(4‐methylbenzylidene)indolin‐2‐one ( 4a ) are used as key precursors for the synthesis of bioactive molecules; [ 1a,18 ] and ( E )‐3‐(3,4,5‐trimethoxybenzylidene)indolin‐2‐one ( 4g ) is employed as precursor for the preparation of cyanide‐scavenging material.…”

Overview of Chemistry and Therapeutic Potential of Non-Nitrogen Heterocyclics as Anticonvulsant Agents

“…injection into mice. It also showed a high protective index (TD 50 /ED 50 ) = 23.4 as compared to the reference antiepileptic drugs i.e., phenytoin (6.9) and phenobarbital (3.2) [ 105 ] (Scheme 48 ). Calderon et al , synthesized a series of 1-phenylcycloalkanecarboxylic acid analogs with moderate to good percentage yield (27-55%).…”