111300-06-2Relevant articles and documents
Explorations of substituted urea functionality for the discovery of new activators of the heme-regulated inhibitor kinase
Chen, Ting,Takrouri, Khuloud,Hee-Hwang, Sung,Rana, Sandeep,Yefidoff-Freedman, Revital,Halperin, Jose,Natarajan, Amarnath,Morisseau, Christophe,Hammock, Bruce,Chorev, Michael,Aktas, Bertal H.
, p. 9457 - 9470 (2013)
Heme-regulated inhibitor kinase (HRI), a eukaryotic translation initiation factor 2 alpha (eIF2α) kinase, plays critical roles in cell proliferation, differentiation, and adaptation to cytoplasmic stress. HRI is also a critical modifier of hemoglobin disorders such as β-thalassemia. We previously identified N,N′-diarylureas as potent activators of HRI suitable for studying the biology of this important kinase. To expand the repertoire of chemotypes that activate HRI, we screened a ～1900 member N,N′-disubstituted urea library in the surrogate eIF2α phosphorylation assay, identifying N-aryl,N′-cyclohexylphenoxyurea as a promising scaffold. We validated hit compounds as a bona fide HRI activators in secondary assays and explored the contributions of substitutions on the N-aryl and N′-cyclohexylphenoxy groups to their activity by studying focused libraries of complementing analogues. We tested these N-aryl,N′- cyclohexylphenoxyureas in the surrogate eIF2α phosphorylation and cell proliferation assays, demonstrating significantly improved bioactivities and specificities. We consider these compounds to represent lead candidates for the development of potent and specific HRI activators.
ALKYNYL QUINAZOLINE COMPOUNDS
-
Paragraph 1094, (2021/02/19)
The present disclosure relates to compounds of Formula (I'): and pharmaceutically acceptable salts and stereoisomers thereof. The present disclosure also relates to methods of preparation these compounds, compositions comprising these compounds, and methods of using them in the prevention or treatment of abnormal cell growth in mammals, especially humans.
Catalytic Transfer Hydrogenation of Arenes and Heteroarenes
Gelis, Coralie,Heusler, Arne,Nairoukh, Zackaria,Glorius, Frank
supporting information, p. 14090 - 14094 (2020/10/19)
Transfer hydrogenation reactions are of great interest to reduce diverse molecules under mild reaction conditions. To date, this type of reaction has only been successfully applied to alkenes, alkynes and polarized unsaturated compounds such as ketones, imines, pyridines, etc. The reduction of benzene derivatives by transfer hydrogenation has never been described, which is likely due to the high energy barrier required to dearomatize these compounds. In this context, we have developed a catalytic transfer hydrogenation reaction for the reduction of benzene derivatives and heteroarenes to form complex 3-dimensional scaffolds bearing various functional groups at room temperature without needing compressed hydrogen gas.
Photoinduced Deoxygenative Borylations of Aliphatic Alcohols
Wu, Jingjing,B?r, Robin M.,Guo, Lin,Noble, Adam,Aggarwal, Varinder K.
supporting information, p. 18830 - 18834 (2019/11/22)
A photochemical method for converting aliphatic alcohols into boronic esters is described. Preactivation of the alcohol as a 2-iodophenyl-thionocarbonate enables a novel Barton–McCombie-type radical deoxygenation that proceeds efficiently with visible light irradiation and without the requirement for a photocatalyst, a radical initiator, or tin or silicon hydrides. The resultant alkyl radical is intercepted by bis(catecholato)diboron, furnishing boronic esters from a diverse range of structurally complex alcohols.
