204849-85-4Relevant academic research and scientific papers
Palladium(0)-catalyzed carbon-Hydrogen bond functionalization for the synthesis of indoloquinazolinones
Tsukano, Chihiro,Okuno, Masataka,Nishiguchi, Hiromi,Takemoto, Yoshiji
, p. 1533 - 1538 (2014/06/09)
The indoloquinazolinone ring system has attracted considerable attention as a pharmacophore, because it shows various biological activities. The reported synthetic methods for the compound are simple and direct, but are not effective for the direct synthesis of indoloquinazolinone with a methylene group at the C-6 position. A palladium(0)-catalyzed cyclization of chloroquinazolinone via C-H functionalization was developed for a concise synthesis of indoloquinazolinone derivatives. The presence of a substituent at the C-6 position is important for obtaining the product in good yield. The conformation of the reaction intermediate, in particular the N-C-Pd bond angle, is important for the regioselectivity of the reaction.
Specific nonpeptide inhibitors of puromycin-sensitive aminopeptidase with a 2,4(1H,3H)-quinazolinedione skeleton.
Kakuta, Hiroki,Tanatani, Aya,Nagasawa, Kazuo,Hashimoto, Yuichi
, p. 1273 - 1282 (2007/10/03)
Potent, specific, chemically stable and non-peptide/small-molecular inhibitors of puromycin-sensitive aminopeptidase, such as 3-(2,6-diethylphenyl)-2,4(1H,3H)-quinazolinedione (PAQ-22, 5), were prepared by the structural development of a potent PSA inhibitor, 2-(2,6-diethylphenyl)-1,2,3,4-tetrahydroisoquinoline-1,3-dione (PIQ-22, 4). The design was carried out partly by applying electrostatic potential field information obtained from PIQ-22 (4) and its derivatives based on thalidomide (2). This information revealed that a positive electrostatic potential field around the benzylic methylene in the tetrahydroisoquinoline ring is necessary for potent activity. Lineweaver-Burk plot analysis showed that PAQ-22 (5) and its derivatives inhibit puromycin-sensitive aminopeptidase (PSA) in a non-competitive manner. These potent and specific PSA inhibitors showed dose-dependent cell invasion-inhibitory activity in a Matrigel assay using mouse melanoma B16F10/L5 cells, in spite of their low cell toxicity.
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).
