204850-17-9Relevant academic research and scientific papers
Design and Synthesis of Selurampanel, a Novel Orally Active and Competitive AMPA Receptor Antagonist
Orain, David,Tasdelen, Engin,Haessig, Samuel,Koller, Manuel,Picard, Anne,Dubois, Celine,Lingenhoehl, Kurt,Desrayaud, Sandrine,Floersheim, Phillip,Carcache, David,Urwyler, Stephan,Kallen, Joerg,Mattes, Henri
, p. 197 - 201 (2017/02/15)
A series of potent quinazolinedione sulfonamide antagonists of the α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor were designed and synthesized. The structure–activity relationships (SAR) and in vivo activity of the series were investigated. In particular, compound 1 S (selurampanel; N-[7-isopropyl-6-(2-methylpyrazol-3-yl)-2,4-dioxo-1H-quinazolin-3-yl]methanesulfonamide) has shown excellent oral potency against maximal electroshock seizure (MES)-induced generalized tonic–clonic seizures in rodents as well as significant activity in patients suffering from various forms of epilepsy. The X-ray crystal structure of selurampanel bound to the AMPA receptor hGluA was also obtained.
Identification and biological characterization of 6-aryl-7- isopropylquinazolinones as novel TRPV1 antagonists that are effective in models of chronic pain
Culshaw, Andrew J.,Bevan, Stuart,Christiansen, Martin,Copp, Prafula,Davis, Andrew,Davis, Clare,Dyson, Alex,Dziadulewicz, Edward K.,Edwards, Lee,Eggelte, Hendrikus,Fox, Alyson,Gentry, Clive,Groarke, Alex,Hallett, Allan,Hart, Terance W.,Hughes, Glyn A.,Knights, Sally,Kotsonis, Peter,Lee, Wai,Lyothier, Isabelle,McBryde, Andrew,McIntyre, Peter,Paloumbis, George,Panesar, Moh,Patel, Sadhana,Seiler, Max-Peter,Yaqoob, Mohammed,Zimmermann, Kaspar
, p. 471 - 474 (2007/10/03)
Vanilloid receptor 1 (VR1, TRPV1) is a cation-selective ion channel that is expressed on primary afferent neurons and is upregulated following inflammation and nerve damage. Blockers of this channel may have utility in the treatment of chronic nociceptive
QUINAZOLINONE DERIVATIVES USEFUL AS ANTI-HYPERALGESIC AGENTS
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, (2010/02/06)
The present invention relates to quinazolinones of formula (I) wherein R1 is hal; a); b); or c); X is N or CR8; R2 is hal; nitro; C1-C6alkylcarbonyl; C1-C6alkyl or C3-C6cycloalkyl; R3 is C1-C6alkyl; C1-C6alkoxy or amino; and wherein the further radicals have the meanings as defined in the specification, which compounds exhibit human vanilloid antagonistic activity; to processes for their production, their use as pharmaceuticals and to pharmaceutical compositions comprising them.
2-amino-4H-3,1-benzoxazin-4-ones as inhibitors of C1r serine protease
Hays, Sheryl J.,Caprathe, Bradley W.,Gilmore, John L.,Amin, Nilam,Emmerling, Mark R.,Michael, Walter,Nadimpalli, Ravi,Nath, Rathna,Raser, Kadee J.,Stafford, Daniel,Watson, Desiree,Wang, Kevin,Jaen, Juan C.
, p. 1060 - 1067 (2007/10/03)
A series of 2-amino-4H-3,1-benzoxazin-4-ones have been synthesized and evaluated as inhibitors of the complement enzyme C1r. C1r is a serine protease at the beginning of the complement cascade, and complement activation by β-amyloid may represent a major contributing pathway to the neuropathology of Alzheimer's disease. Compounds such as 7-chloro-2-[(2- iodophenyl)amino]benz[d][1,3]oxazin-4-one (32) and 7-methyl-2-[(2- iodophenyl)amino]benz[d][1,3]oxazin-4-one (37) show improved potency compared to the reference compound FUT-175. Many of these active compounds also possess increased selectivity for C1r compared to trypsin and enhanced hydrolytic stability relative to 2-(2-iodophenyl)-4H-3,1-benzoxazin-4-one (1).
