342002-85-1Relevant academic research and scientific papers
Rescuing the CFTR protein function: Introducing 1,3,4-oxadiazoles as translational readthrough inducing drugs
Pibiri, Ivana,Lentini, Laura,Melfi, Raffaella,Tutone, Marco,Baldassano, Sara,Ricco Galluzzo, Paola,Di Leonardo, Aldo,Pace, Andrea
, p. 126 - 142 (2018)
Nonsense mutations in the CFTR gene prematurely terminate translation of the CFTR mRNA leading to the production of a truncated protein that lacks normal function causing a more severe form of the cystic fibrosis (CF) disease. About 10% of patients affected by CF show a nonsense mutation. A potential treatment of this alteration is to promote translational readthrough of premature termination codons (PTCs) by Translational Readthrough Inducing Drugs (TRIDs) such as PTC124. In this context we aimed to compare the activity of PTC124 with analogues differing in the heteroatoms position in the central heterocyclic core. By a validated protocol consisting of computational screening, synthesis and biological tests we identified a new small molecule (NV2445) with 1,3,4-oxadiazole core showing a high readthrough activity. Moreover, we evaluated the CFTR functionality after NV2445 treatment in CF model systems and in cells expressing a nonsense-CFTR-mRNA. Finally, we studied the supramolecular interactions between TRIDs and CFTR-mRNA to assess the biological target/mechanism and compared the predicted ADME properties of NV2445 and PTC124.
Synthesis of amino-diamondoid pharmacophores: Via photocatalytic C-H aminoalkylation
Weigel, William K.,Dang, Hoang T.,Yang, Hai-Bin,Martin, David B. C.
supporting information, p. 9699 - 9702 (2020/09/03)
We report a direct C-H aminoalkylation reaction using two light-activated H-atom transfer catalyst systems that enable the introduction of protected amines to native adamantane scaffolds with C-C bond formation. The scope of adamantane and imine reaction partners is broad and deprotection provides versatile amine and amino acid building blocks. Using readily available chiral imines, the enantioselective synthesis of the saxagliptin core and rimantadine derivatives is also described.
Cu(II) catalyzed imine C-H functionalization leading to synthesis of 2,5-substituted 1,3,4-oxadiazoles
Guin, Srimanta,Ghosh, Tuhin,Rout, Saroj Kumar,Banerjee, Arghya,Patel, Bhisma K.
supporting information; body text, p. 5976 - 5979 (2012/01/02)
A direct access to symmetrical and unsymmetrical 2,5-disubstituted [1,3,4]-oxadiazoles has been accomplished through an imine C-H functionalization of N-arylidenearoylhydrazide using a catalytic quantity of Cu(OTf)2. This is the first example of amidic oxygen functioning as a nucleophile in a Cu-catalyzed oxidative coupling of an imine C-H bond. These reactions can be performed in air atmosphere and moisture making it exceptionally practical for application in organic synthesis.
