941598-93-2Relevant academic research and scientific papers
Discovery and validation of 2-styryl substituted benzoxazin-4-ones as a novel scaffold for rhomboid protease inhibitors
Goel, Parul,Jumpertz, Thorsten,Tichá, Ane?ka,Ogorek, Isabella,Mikles, David C.,Hubalek, Martin,Pietrzik, Claus U.,Strisovsky, Kvido,Schmidt, Boris,Weggen, Sascha
, p. 1417 - 1422 (2018)
Rhomboids are intramembrane serine proteases with diverse physiological functions in organisms ranging from archaea to humans. Crystal structure analysis has provided a detailed understanding of the catalytic mechanism, and rhomboids have been implicated in various disease contexts. Unfortunately, the design of specific rhomboid inhibitors has lagged behind, and previously described small molecule inhibitors displayed insufficient potency and/or selectivity. Using a computer-aided approach, we focused on the discovery of novel scaffolds with reduced liabilities and the possibility for broad structural variations. Docking studies with the E. coli rhomboid GlpG indicated that 2-styryl substituted benzoxazinones might comprise novel rhomboid inhibitors. Protease in vitro assays confirmed activity of 2-styryl substituted benzoxazinones against GlpG but not against the soluble serine protease α-chymotrypsin. Furthermore, mass spectrometry analysis demonstrated covalent modification of the catalytic residue Ser201, corroborating the predicted mechanism of inhibition and the formation of an acyl enzyme intermediate. In conclusion, 2-styryl substituted benzoxazinones are a novel rhomboid inhibitor scaffold with ample opportunity for optimization.
A comparative study of solution phase as well as solvent free microwave assisted syntheses of 3-benzothiazole/isoxazole substituted 2-styryl-4(3H)- quinazolinones
Jagani, Chandresh L.,Vanparia, Satish F.,Patel, Tarosh S.,Dixit, Ritu B.,Dixit, Bharat C.
experimental part, p. 281 - 294 (2012/06/30)
An optimization of the reaction conditions in solvent free and solution phase microwave assisted synthesis of 2-styryl-4(3H)-quinazolinone derivatives having substituted benzothiazole/5-tert-butylisoxazole at the 3rd position is discussed. In solvent free reactions acidic alumina was used as a solid support, while a mixture of DMF and pyridine was used in solution phase synthesis. A comparative study of yield and reaction time for both the optimized method revealed that the solution phase microwave irradiation gave better results than solvent free method. ARKAT-USA, Inc.
