Regioselective synthesis of 7,8-dihydroimidazo[5,1-c][1,2,4]triazine-3,6(2H,4H)-dione derivatives: A new drug-like heterocyclic scaffold

• Nikolay T. Tzvetkov,
• Harald Euler and
• Christa E. Müller

Beilstein J. Org. Chem. 2012, 8, 1584–1593, doi:10.3762/bjoc.8.181

• involved [3]. Recently, specifically substituted imidazo[1,5-f][1,2,4]triazines (4) have been developed as polo-like kinase (PLK) inhibitors with potential as anticancer therapeutics [10]. The 1,2,4-triazines 4 also exhibited inhibitory activities against glycogen synthase kinase 3 (GSK3β), and may

An intramolecular inverse electron demand Diels–Alder approach to annulated α-carbolines

• Zhiyuan Ma,
• Feng Ni,
• Grace H. C. Woo,
• Sie-Mun Lo,
• Philip M. Roveto,
• Scott E. Schaus and
• John K. Snyder

Beilstein J. Org. Chem. 2012, 8, 829–840, doi:10.3762/bjoc.8.93

• Intramolecular inverse electron demand cycloadditions of isatin-derived 1,2,4-triazines with acetylenic dienophiles tethered by amidations or transesterifications proceed in excellent yields to produce lactam- or lactone-fused α-carbolines. Beginning with various isatins and alkynyl dienophiles, a pilot-scale

• library of annulated α-carboline structures 6 could be prepared by the intramolecular inverse electron demand Diels–Alder reaction (IEDDA) of isatin-derived 1,2,4-triazines 7 with tethered electron-rich dienophiles (Scheme 1) [69]. Inverse electron demand Diels–Alder cycloadditions employing electron

• to be important for the subsequent cycloaddition to proceed, as was shown to be correct in later studies. Furthermore, sulfonylation greatly improved the solubility of the triazines 8 in organic solvents in comparison to 9, which showed only limited solubility in dichloromethane, chloroform, THF