35345-15-4Relevant articles and documents
Modular Synthesis of Di- A nd Trisubstituted Imidazoles from Ketones and Aldehydes: A Route to Kinase Inhibitors
De Toledo, Ian,Grigolo, Thiago A.,Bennett, James M.,Elkins, Jonathan M.,Pilli, Ronaldo A.
, p. 14187 - 14201 (2019/10/16)
A one-pot and modular approach to the synthesis of 2,4(5)-disubstituted imidazoles was developed based on ketone oxidation, employing catalytic HBr and DMSO, followed by imidazole condensation with aldehydes. This methodology afforded twenty-nine disubstituted NH-imidazoles (23%-85% yield). A three-step synthesis of 20 kinase inhibitors was achieved by employing this oxidation-condensation protocol, followed by bromination and Suzuki coupling in the imidazole ring to yield trisubstituted NH-imidazoles (23%-69%, three steps). This approach was also employed in the synthesis of known inhibitor GSK3037619A.
Anticonvulsant activity of 2,4(1H)-diarylimidazoles in mice and rats acute seizure models
Zuliani, Valentina,Fantini, Marco,Nigam, Aradhya,Stables, James P.,Patel, Manoj K.,Rivara, Mirko
experimental part, p. 7957 - 7965 (2011/01/13)
2,4(1H)-Diarylimidazoles have been previously shown to inhibit hNa V1.2 sodium (Na) channel currents. Since many of the clinically used anticonvulsants are known to inhibit Na channels as an important mechanism of their action, these compounds were tested in two acute rodent seizure models for anticonvulsant activity (MES and scMet) and for sedative and ataxic side effects. Compounds exhibiting antiepileptic activity were further tested to establish a dose response curve (ED50). The experimental data identified four compounds with anticonvulsant activity in the MES acute seizure rodent model (compound 10, ED50 = 61.7 mg/kg; compound 13, ED 50 = 46.8 mg/kg, compound 17, ED50 = 129.5 mg/kg and compound 20, ED50 = 136.7 mg/kg). Protective indexes (PI = TD 50/ED50) ranged from 2.1 (compound 10) to greater than 3.6 (compounds 13, 17 and 20). All four compounds were shown to inhibit hNa V1.2 in a dose dependant manner. Even if a correlation between sodium channel inhibition and anticonvulsant activity was unclear, these studies identify four Na channel antagonists with anticonvulsant activity, providing evidence that these derivatives could be potential drug candidates for development as safe, new and effective antiepileptic drugs (AEDs).
