113283-94-6Relevant academic research and scientific papers
Synthesis and structure-activity relationships of small-molecular di-basic esters, amides and carbamates as flaviviral protease inhibitors
Sundermann, Tom R.,Benzin, Clarissa V.,Dra?i?, Tonko,Klein, Christian D.
, p. 187 - 194 (2019/05/21)
Inhibitors of the flaviviral serine proteases, which are crucial for the replication of dengue and West-Nile virus, have attracted much attention over the last years. A dibasic 4-guanidinobenzoate was previously reported as inhibitor of the dengue protease with potency in the low-micromolar range. In the present study, this lead structure was modified with the intent to explore structure-activity relationships and obtain compounds with increased drug-likeness. Substitutions of the guanidine moieties, the aromatic rings, and the ester with other functionalities were evaluated. All changes were accompanied by a loss of inhibition, indicating that the 4-guanidinobenzoate scaffold is an essential element of this compound class. Further experiments indicate that the target recognition of the compounds involves the reversible formation of a covalent adduct.
Synthesis and biological characterisation of sirtuin inhibitors based on the tenovins
McCarthy, Anna R.,Pirrie, Lisa,Hollick, Jonathan J.,Ronseaux, Sebastien,Campbell, Johanna,Higgins, Maureen,Staples, Oliver D.,Tran, Fanny,Slawin, Alexandra M.Z.,Lain, Sonia,Westwood, Nicholas J.
, p. 1779 - 1793 (2012/04/17)
The tenovins are small molecule inhibitors of the NAD+-dependent family of protein deacetylases known as the sirtuins. There remains considerable interest in inhibitors of this enzyme family due to possible applications in both cancer and neuro
a2-Adrenoceptor Ligands
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Page/Page column 8, (2010/07/04)
The adrenergic receptors or adrenoceptors are a family of G-protein coupled receptors split into α and β subclasses. The adrenoceptors have important roles in regulating a myriad of physiological conditions and their malfunction has been implicated in the pathophysiology of a number of diseases. Disclosed herein are a series of novel compounds which are ligands of the alpha2-adrenoceptor (α2-ARs) subclass of adrenergic receptors. The invention also provides for pharmaceutical compositions comprising the novel compounds. The compounds are suitable for use in the manufacture of medicaments for the treatment of α2-ARs associated disorders, such as depression and schizophrenia.
Guanidine and 2-aminoimidazoline aromatic derivatives as α2-adrenoceptor ligands: Searching for structure-activity relationships
Rodriguez, Fernando,Rozas, Isabel,Ortega, Jorge E.,Erdozain, Amaia M.,Meana, J. Javier,Callado, Luis F.
supporting information; experimental part, p. 601 - 609 (2009/11/30)
In this paper, we report the synthesis of three new 2-aminoimidazoline (compounds 4b, 5b, and 6b) and three new guanidine derivatives (compounds 7b, 8b, and 9b) as potential α2-adrenoceptor antagonists for the treatment of depression. Their pha
Arylisothiocyanato selective androgen receptor modulators (SARMs) for prostate cancer
Hwang, Dong Jin,Yang, Jun,Xu, Huiping,Rakov, Igor M.,Mohler, Michael L.,Dalton, James T.,Miller, Duane D.
, p. 6525 - 6538 (2007/10/03)
A new series of androgen receptor targeted agents (ARTA) was prepared and tested in androgen-dependent and -independent prostate cancer cell lines. These agents were bicalutamide analogs with isothiocyanato substituted B-rings. Also, the linker sulfone of R-bicalutamide was maintained or replaced with several alternative linkages including ether, amine, N-methylamine, thioether, and methylene (in this case the product was a racemic mixture) functional groups at the X-position. To expand the structure-activity relationship (SAR) of these arylisothiocyanato AR ligands, B-ring halogenated arylisothiocyanato ligands were also prepared and tested. The arylisothiocyanato AR ligands showed strong binding affinities to AR ranging from 0.6 to 54 nM. Among them, thioether and ether linkages demonstrated high binding affinities (0.6 and 4.6 nM, respectively) and selective cell growth inhibition (approximately 3- to 6-fold) for LNCaP, an androgen-dependent prostate cancer cell line, when compared to the androgen independent prostate cell lines (DU145, PC-3, and PPC-1) and a bladder cell line (TSU-Pr1). However, the ligands were inactive (IC50>100 mM) in a normal monkey kidney cell line (CV-1) that was used as the control for non-specific toxicity.
1-[4-(N-chlorocarbonyl-N-methylamino)phenyl]-2-(phenylsulfonyl)diazene , a bifunctional reagent with a protected diazonium function
Kessler,Chatrenet,Goeldner,Hirth
, p. 1065 - 1068 (2007/10/02)
1-[4-(N-Chlorocarbonyl-N-methylamino)phenyl]-2-(phenylsulfonyl)diazene is the first bifunctional reagent containing a potential photoactivatable arenediazonium function. The synthesis and the chemical properties of the reagent are described, in particular
Selective Protection of Polyamines: Synthesis of Model Compounds and Spermidine Derivatives
Lurdes, M.,Almieda, S.,Grehn, Leif,Ragnarsson, Ulf
, p. 1905 - 1912 (2007/10/02)
A general procedure for the selective protection of mixed-primary-secondary (poly)amines, based on t-butoxycarbonylation of carbamate groups (exhaustive t-butoxycarbonylation) derived from the primary amino functions only, is reported.In most cases to be described, benzyl (poly)carbamates are used for this purpose.Subsequent removal of all benzyloxycarbonyl (Z) groups from the resulting intermediates by catalytic hydrogenolysis liberates the secondary amino functions, while t-butoxycarbonyl (Boc) is retained on the primary ones.Alternatively, selective removal of Z only from amino functions protected by both Z and Boc, which can be accomplished by base-catalysed methanolysis, results in protected (poly)amines with Boc and Z on their primary and secondary amino groups, respectively.The new reactions have been studied with two unsymmetrical derivatives of ethylene- and p-phenylene-diamine as model substances.The yields of most intermediates and the products were high.Additional experiments have been performed with spermidine to give N1,N8-Boc2-spermidine.Finally, by virtue of the non-equivalence of the two primary amino groups in this molecule, the synthesis of N8-Boc-N1-Z-spermidine by the same approach is presented.
Selective Protection of Mixed Primary-Secondary Amines. Simple Preparation of N1,N8-Bis(t-butoxycarbonyl)spermidine
Lurdes, M.,Almeida, S.,Grehn, Leif,Ragnarsson, Ulf
, p. 1250 - 1251 (2007/10/02)
A new, simple, and efficient preparative procedure of a potentially wide scope for the selective protection of mixed primary-secondary amines, based on acylation followed by exhaustive t-butoxycarbonylation is presented.
