5751-20-2Relevant articles and documents
Sulfenyl Ynamides in Gold Catalysis: Synthesis of Oxo-functionalised 4-aminoimidazolyl Fused Compounds by Intermolecular Annulation Reactions
Arce, Elsa M.,Lamont, Scott G.,Davies, Paul W.
, p. 2503 - 2509 (2020/04/30)
Functionalised N-heterocyclic pyridinium N-aminides have been designed and synthesised to evaluate a nitrenoid-based annulation strategy into imidazole-fused oxo-substituted frameworks of importance to medicinal and agrochemical discovery programmes. Sulfenyl substituted ynamides were identified as privileged reactants affording productive gold-catalysed annulation reactions with these and other nitrenoids. This annulation method provides selective and efficient access into geminally amino-sulfenyl substituted nitrogen heterocycles under mild reaction conditions. (Figure presented.).
Design of biphenyl-substituted diarylpyrimidines with a cyanomethyl linker as HIV-1 NNRTIs via a molecular hybridization strategy
Chen, Fen-Er,Han, Sheng,Lei, Yuan,Pannecouque, Christophe,Yang, Yang,Zhuang, Chunlin,de Clercq, Erik
, (2020/03/17)
The key problems of human immunodeficiency virus (HIV) therapy are the rapid emergence of drug-resistant mutant strains and significant cumulative drug toxicities. Therefore, there is an urgent demand for new anti-HIV agents with low toxicity and broad-spectrum antiviral potency. A series of biphenyl-substituted diarylpyrimidines with a cyanomethyl linker were designed using a molecular hybridization strategy. The cell-based anti-HIV assay showed that most of the compounds exhibited moderate to good activities against wild-type HIV-1 and clinically relevant mutant strains with a more favorable toxicity, and the enzymatic assay showed they had nanomolar activity against reverse transcriptase (RT). Compound 10p exhibited the best activity against wild-type HIV-1 with an EC50 (50% HIV-1 replication inhibitory concentration) value of 0.027 μM, an acceptable CC50 (50% cytotoxic concentration) value of 36.4 μM, and selectivity index of 1361, with moderate activities against the single mutants (EC50: E138K, 0.17 μM; Y181C, 0.87 μM; K103N, 0.9 μM; L100I, 1.21 μM, respectively), and an IC50 value of 0.059 μM against the RT enzyme, which was six-fold higher than nevirapine (NVP). The preliminary structure–activity relationship (SAR) of these new compounds was concluded. The molecular modeling predicted the binding modes of the new compounds with RT, providing molecular insight for further drug design.
BF3·SMe2 for Thiomethylation, Nitro Reduction and Tandem Reduction/SMe Insertion of Nitrogen Heterocycles
S?derstr?m, Marcus,Zamaratski, Edouard,Odell, Luke R.
, p. 5402 - 5408 (2019/06/27)
Herein, a general, solvent-free and straightforward thiomethylation of electron deficient heterocycles using BF3·SMe2 as a dual thiomethyl source and Lewis acidic activator is presented. A range of heterocycles including pyrimidine, pyrazine, pyridazine, thiazole and purine derivatives were successfully substituted using this method. An unexpected reductive property of BF3·SMe2 towards nitropyridines was also discovered including an intriguing tandem reduction/SMe insertion process in certain substrates. Notable features of the present work include its convenience and use of a non-malodorous reagent while the discovery of novel chemical transformations using BF3·SMe2 provides fundamental new insights into the reactivity of this commonly employed reagent.