Rapid Microwave-Assisted Solution Phase Synthesis of 6,8-Disubstituted 2-Phenyl-3-(substituted- benzothiazol-2-yl)-4-[3H]-quinazolinones as Novel Anticonvulsants

Abstract

A fast and highly efficient microwave accelerated solution phase procedure for the synthesis of a series of 2-phenyl-3-(benzothiazol-2-yl)-4[3H]-quinazolinones, substituted in the benzothiazole ring, is developed. The title compounds were characterized by elemental analyses, IR, 1 H NMR, and EI-MS data. The anticonvulsant activity of all the new compounds (3a-m and 4a-m) was evaluated against Maximum Electroshock (MES) induced seizures and against subcutaneous pentylenetetrazole (PTZ) induced seizures model in mice.The neurotoxicity was assessed using the Rotorod procedure. All the compounds tested were administered intraperitoneally at a various dose levels ranging from 7-200 mg/Kg body weight and the median toxic dose (TD 50 ) and the protection index (PI) values were determined. In general compounds 3a-m were found to be more potent compared to compounds 4a-m. Among the compound tested, the compound 3e in the 2-phenyl-3-(benzothiazole-2-yl)-4[3H]-quinazolinone series and 4l in the 6,8-dibromo-2-phenyl-3-(benzothiazole-2-yl)-4[3H]-quinazolinone series were found to be the most potent.

A comprehensive review in current developments of benzothiazole-based molecules in medicinal chemistry

“…Compounds (187) were found most potent: ED 50 ¼ 7.1 and 12.8 in MES model and 10 and 14 in scPTZ model at t ¼ 0.5 h and 4 h, respectively, and TD 50 ¼ 37.8 and 43 at t ¼ 0.5 h and 4 h, respectively, with protection index (PI) 5.3. The presence of electron withdrawing groups (halogen and nitro) at the aromatic ring in general decreases the potency compared to compounds having electron-donating groups [221]. BTA-oxoquinazoline carbothioamide derivatives were synthesized by Malik et al, for evaluation of their anticonvulsant effects were done using various models of experimental epilepsy.…”

A new therapeutic approach in Parkinson’s disease: Some novel quinazoline derivatives as dual selective phosphodiesterase 1 inhibitors and anti-inflammatory agents

“…The compound with R1 = electron releasing groups was showed more PDE1 inhibitory activity than the compounds with R1 = electron withdrawing groups. This type of effect was mainly observed in compound [16][17][18][19][20][21][22]. Among all the compounds in this series, 9,11-dibromo-1- …”

“…Continuing our studies on quinazolinone derivatives 14,17,19,41,42 that are attractive candidates as PDE1 inhibitors, and anti-inflammatory agents, we have designed a novel thienopyrimidine fused quinazolinones and pyridopyrimidine fused quinazolinones. This dual PDE1 inhibitor/anti-inflammatory offers advantages beyond simple additive effects of administration of the individual agents including providing greater symptomatic efficacy and better utility.…”

“…The quinazolinone moiety is a building block for approximately 150 naturally occurring alkaloids and drugs. 10 The natural quinazolinones and their synthetic analogs possess a variety of biological activities, including PDE inhibitory activity, [11][12][13][14][15] anticonvulsant, 16,17 bronchodilator, 18 anti-inflammatory, 19,20 antimalarial, 21 antituberculous, 22 anti-HIV, 23 narcotic antagonist, 24 anti-tumor, 25 tyrosine kinase inhibitor, 26 adenosine antagonist, 27 antimicrobial, 19 etc. Along with these activities, quinazoline derivatives showed a very prominent activity in PD.…”

Efficient Niementowski synthesis of novel derivatives of 1,2,9,11-tetrasubstituted-7H-thieno[2',3':4,5]pyrimido[6,1-b]-quinazolin-7-one

“…Rutaecarpine 22 and Luotonine A 23 ( Figure 1), the two natural quinazoline fused compounds exhibit a very potent pharmacological values. In search of new fused heterocyclic compounds with potential pharmaceutical value and in association with our work 13,[24][25][26] on the application of microwaves in organic chemistry, we planned to prepare novel tetracyclic 1,2,9,11-tetrasubstituted-7H-thieno [2',3':4,5]pyrimido [6,1-b]quinazolin-7-ones (5), from the reaction between anthranilic acids (4) and thieno [2,3-d]pyrimidine rings (3). The synthesis of various congeners took place via a Niementowski condensation, inspired by Alexandre and coworkers.…”