33876-92-5Relevant academic research and scientific papers
Promiscuity and selectivity in covalent enzyme inhibition: A systematic study of electrophilic fragments
J?st, Christian,Nitsche, Christoph,Scholz, Therese,Roux, Lionel,Klein, Christian D.
supporting information, p. 7590 - 7599 (2014/12/11)
Covalent ligand-target interactions offer significant pharmacological advantages. However, off-target reactivity of the reactive groups, which usually have electrophilic properties, must be minimized, and the selectivity of irreversible inhibitors is a crucial requirement. We therefore performed a systematic study to determine the selectivity of several electrophilic groups that can be used as building blocks for covalently binding ligands. Six reactive groups with modulated electrophilicity were combined with 11 nonreactive moieties, resulting in a small combinatorial library of 72 fragment-like compounds. These compounds were screened against a group of 11 enzyme targets to assess their selectivity and their potential for promiscuous binding to proteins. The assay results showed a considerably lower degree of promiscuity than initially expected, even for those members of the screening collection that contain supposedly highly reactive electrophiles.
Interaction of 2-naphthol with γ-ureidoacetals. A new method for the synthesis of 2-arylpyrrolidines
Gazizov,Smolobochkin,Burilov,Pudovik
, p. 707 - 714 (2014/08/18)
We report a new, single-stage method for the synthesis of 2-arylpyrrolidines, based on an acid-catalyzed reaction of 2-naphthol with γ-ureidoacetals, enabling the preparation of the target compounds under mild conditions, while avoiding costly reagents an
Reaction of 1-aryl-3-(4,4-diethoxybutyl)ureas with phenols. Synthesis of 2-arylpyrrolidines
Gazizov, A. S.,Burilov, A. R.,Pudovik, M. A.,Smolobochkin, A. V.
, p. 1809 - 1813 (2015/02/02)
Acid-catalyzed reaction of phenols with 1-(4,4-diethoxybutyl)urea derivatives gave new 2-arylpyrrolidines containing 4-bromoresorcinol and hydroquinone fragments. The described reaction is advantageous due to its mild conditions and no necessity of using
Synthesis of unsymmetrical biaryl ureas from N-carbamoylimidazoles: Kinetics and application
Rawling, Tristan,McDonagh, Andrew M.,Tattam, Bruce,Murray, Michael
experimental part, p. 6065 - 6070 (2012/09/22)
N-Carbamoylimidazoles dissociate in solution to yield imidazole and an isocyanate that may be reacted with another aryl amine to form an unsymmetrical biaryl urea. This paper investigates the reaction kinetics and the influence of electron withdrawing/donating substituents on the reaction of N-carbamoylimidazoles with aniline. The overall reaction mechanism involves two zwitterionic intermediates, formed during dissociation and upon reaction of the liberated isocyanate with aniline. The rate limiting step for the reaction is a base catalysed proton transfer from the second zwitterionic intermediate. Although electron withdrawing substituents on the aryl group hinder dissociation, they significantly increase reaction rates compared to compounds bearing electron donating substituents. The imidazole liberated upon dissociation catalyses the rate determining step so that reactions of dissociated N-carbamoylimidazoles proceed more rapidly than those involving only isocyanates. In addition, the imidazole eliminates the need for anhydrous reaction conditions. The N-carbamoylimidazole methodology was demonstrated by preparing sorafenib, a biaryl urea kinase inhibitor, in good yield and excellent purity.
Unprecedented "in water" imidazole carbonylation: Paradigm shift for preparation of urea and carbamate
Padiya, Kamlesh J.,Gavade, Sandip,Kardile, Bhavana,Tiwari, Manojkumar,Bajare, Swapnil,Mane, Madhav,Gaware, Vivek,Varghese, Shaji,Harel, Dipak,Kurhade, Suresh
supporting information; experimental part, p. 2814 - 2817 (2012/08/07)
The first "In Water" imidazolecarbonylation of amine is described. A one pot reaction of carbonylimidazolide in water with a nucleophile provides an efficient and general method for the preparation of urea, carbamates and thiocarbamates. Use of an anhydrous solvent and an inert atmosphere could be avoided. Product precipitate out from the reaction mixture and can be obtained in high purity by filtration, resulting in a simple and scalable method.
Synthesis and antitumor activity of novel diaryl ether hydroxamic acids derivatives as potential HDAC inhibitors
Zhu, Yong,Chen, Xin,Wu, Zeng,Zheng, Yixuan,Chen, Yadong,Tang, Weifang,Lu, Tao
, p. 1723 - 1732 (2013/03/13)
A series of diaryl ether hydroxamic acids were synthesized for the first time and evaluated for the HDAC biology and antiproliferative activity. The structures of these new hydroxamic acids derivatives were confirmed by IR, 1H-NMR and mass spectrum. Some of these compounds showed micro molar activity in the HDAC inhibitory assay and against four cancer cell lines.
REACTIONS OF ISOTHIOCYANATES AND ISOCYANATES WITH SOME SILYLATED NITROGEN-CONTAINING NUCLEOPHILES
Gonda, Josef,Antalova, Zuzana
, p. 685 - 694 (2007/10/02)
Aryl isothiocyanates and arylisocyanates react with N,O-bis(trimethylsilyl)acetamide to give N-methyl-N'-arylthioureas and ureas.Also nucleophilic additions of other aprotic nucleophiles (e.g.N-trimethylsilylimidazole, N-trimethylsilylpiperidine and N-trimethylsilylmorpholine) to the N=C=X (X=O,S) group were investigated.
