80985-23-5Relevant academic research and scientific papers
Targeting nuclear protein TDP-43 by cell division cycle kinase 7 inhibitors: A new therapeutic approach for amyotrophic lateral sclerosis
Rojas-Prats, Elisa,Martinez-Gonzalez, Loreto,Gonzalo-Consuegra, Claudia,Liachko, Nicole F.,Perez, Concepción,Ramírez, David,Kraemer, Brian C.,Martin-Requero, ángeles,Perez, Daniel I.,Gil, Carmen,de Lago, Eva,Martinez, Ana
supporting information, (2020/11/12)
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with no known cure. Aggregates of the nuclear protein TDP-43 have been recognized as a hallmark of proteinopathy in both familial and sporadic cases of ALS. Post-translational modifications of this protein, include hyperphosphorylation, cause disruption of TDP-43 homeostasis and as a consequence, promotion of its neurotoxicity. Among the kinases involved in these changes, cell division cycle kinase 7 (CDC7) plays an important role by directly phosphorylating TDP-43. In the present manuscript the discovery, synthesis, and optimization of a new family of selective and ATP-competitive CDC7 inhibitors based on 6-mercaptopurine scaffold are described. Moreover, we demonstrate the ability of these inhibitors to reduce TDP-43 phosphorylation in both cell cultures and transgenic animal models such as C. elegans and Prp-hTDP43 (A315T) mice. Altogether, the compounds described here may be useful as versatile tools to explore the role of CDC7 in TDP-43 phosphorylation and also as new drug candidates for the future development of ALS therapies.
On the Tautomerism of 2-Phenacyl-4-pyrimidinones and Related Compounds
Elguero, Jose,Goya, Pilar,Martinez, Ana,Rozas, Isabel
, p. 919 - 924 (2007/10/02)
3-Methyl-2-phenacyl-4-pyrimidinones 1, 2 have been synthesized using the sulfide contraction.According to the NMR data, the compounds 1, 2 exist exclusively as the benzoylmethylene tautomers a both in solution and in the solid state.AM1 calculations of the parent system are in agreement with the experimental observations.The study of the tautomeric equilibrium by this semiempirical method has been extended to other cases of enaminoketone/enolimine tautomerism. - Key Words: Pyrimidinones / Tautomerism / AM1 calculations
