16628-26-5Relevant articles and documents
Structure guided optimization of a fragment hit to imidazopyridine inhibitors of PI3K
Pecchi, Sabina,Ni, Zhi-Jie,Han, Wooseok,Smith, Aaron,Lan, Jiong,Burger, Matthew,Merritt, Hanne,Wiesmann, Marion,Chan, John,Kaufman, Susan,Knapp, Mark S.,Janssen, Johanna,Huh, Kay,Voliva, Charles F.
, p. 4652 - 4656 (2013)
PI3 kinases are a family of lipid kinases mediating numerous cell processes such as proliferation, migration and differentiation. The PI3 Kinase pathway is often de-regulated in cancer through PI3Kα overexpression, gene amplification, mutations and PTEN p
HETEROARYL COMPOUNDS AS NECROSIS INHIBITORS, COMPOSITION AND METHOD USING THE SAME
-
Paragraph 0082-0084, (2020/07/25)
The present disclosure provides heteroaryl compounds of Formula (I), processes for their preparation, pharmaceutical compositions containing them, and their use in the treatment of diseases and disorders, arising from or related to necrosis. Formula (I) i
Medicine with necrocytosis inhibitory activity and application thereof
-
Paragraph 0036-0040, (2018/03/24)
The invention provides a medicine with the necrocytosis inhibitory activity. The medicine with the necrocytosis inhibitory activity contains one or two of the following compounds. The invention further provides application of the medicine with the necrocy
Probing the ATP-Binding Pocket of Protein Kinase DYRK1A with Benzothiazole Fragment Molecules
Rothweiler, Ulli,Stensen, Wenche,Brandsdal, Bj?rn Olav,Isaksson, Johan,Leeson, Frederick Alan,Engh, Richard Alan,Svendsen, John S. Mj?en
, p. 9814 - 9824 (2016/11/19)
DYRK1A has emerged as a potential target for therapies of Alzheimer's disease using small molecules. On the basis of the observation of selective DYRK1A inhibition by firefly d-luciferin, we have explored static and dynamic structural properties of fragment sized variants of the benzothiazole scaffold with respect to DYRK1A using X-ray crystallography and NMR techniques. The compounds have excellent ligand efficiencies and show a remarkable diversity of binding modes in dynamic equilibrium. Binding geometries are determined in part by interactions often considered "weak", including "orthogonal multipolar" types represented by, for example, F-CO, sulfur-aromatic, and halogen-aromatic interactions, together with hydrogen bonds that are modulated by variation of electron withdrawing groups. These studies show how the benzothiazole scaffold is highly promising for the development of therapeutic DYRK1A inhibitors. In addition, the subtleties of the binding interactions, including dynamics, show how full structural studies are required to fully interpret the essential physical determinants of binding.