Synthesis and biological evaluation of 4H-benzo[e][1,3]oxazin-4-ones analogues of TGX-221 as inhibitors of PI3Kβ.

A novel series of TGX-221 analogues was prepared that include isosteric replacement of the 4H-pyrido[1,2-a]pyrimidin-4-one with a 4H-benzo[e][1,3]oxazin-4-one scaffold. The compounds that included an CH(CH)NH type linker showed comparable activity to TGX-221 analogues with the isosterism supported by the comparative SAR analysis. The analogues containing an CH(CH)O linker were less active but still showed useful SAR including a favoured o-methyl substitution.

Universal design for learning for educating students with intellectual disabilities: a systematic review.

This review analyzes studies carried out between 2008 and 2018 which examined the educational impact of interventions based on the Universal Design for Learning (UDL) for students with Intellectual Disabilities (ID). The review aims to determine the research designs and methods of these studies, and their interventions and effectiveness. Seven studies met the inclusion criteria used in this review.

Inhibition of AKT signalling by benzoxazine derivative LTUR6 through the modulation of downstream kinases.

Many compounds structurally similar to chromones have been developed to enhance the sensitizing effect of cancer cells to chemotherapeutic agents. Most of these compounds have been shown to promote this sensitization by targeting the repair pathways. One such compound is LTUR6, which enhances the sensitization of doxorubicin to colon cancer cells HT29, by inhibiting the phosphorylation of the double stranded break (DSB) repair enzyme AKT.

Synthesis and biological evaluation of 8-aryl-2-morpholino-7-O-substituted benzo[e][1,3]oxazin-4-ones against DNA-PK, PI3K, PDE3A enzymes and platelet aggregation.

A series of 40 7-(O-substituted)-2-morpholino-8-aryl-4H-benzo[e][1,3]oxazin-4-one derivatives was synthesized. They were prepared via synthesis of a key precursor, 8-bromo-7-hydroxy-2-morpholino-4H-benzo[e][1,3]oxazin-4-one 13 which was amenable to ether synthesis at the 7-position and Suzuki coupling at the 8-position. The 2 protons of 7-OCH in compounds 18g, 18h, 18i, 18l and 18m prove to be magnetically non-equivalent, atropisomerism (axial chirality), as result of sterically hindered rotation of the bulky 8-aryl-substituent.

Synthesis of linear and angular aryl-morpholino-naphth-oxazines, their DNA-PK, PI3K, PDE3A and antiplatelet activity.

To continue our study of 2-morpholino-benzoxazine based compounds, which show useful activity against PI3K family enzymes or antiplatelet activity, we designed and synthesized a series of linear 6.7-fused, 5,6-angular fused and 7,8-angular fused-aryl-morpholino-naphth-oxazines. The compounds were prepared from substituted 2-hydroxynaphthoic acid to give the corresponding thioxo analogues 8, 9, 15 and 19.