- A scaffold replacement approach towards new sirtuin 2 inhibitors
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Sirtuins (SIRT1–SIRT7) are an evolutionary conserved family of NAD+-dependent protein deacylases regulating the acylation state of ε-N-lysine residues of proteins thereby controlling key biological processes. Numerous studies have found association of the aberrant enzymatic activity of SIRTs with various diseases like diabetes, cancer and neurodegenerative disorders. Previously, we have shown that substituted 2-alkyl-chroman-4-one/chromone derivatives can serve as selective inhibitors of SIRT2 possessing an antiproliferative effect in two human cancer cell lines. In this study, we have explored the bioisosteric replacement of the chroman-4-one/chromone core structure with different less lipophilic bicyclic scaffolds to overcome problems associated to poor physiochemical properties due to a highly lipophilic substitution pattern required for achieve a good inhibitory effect. Various new derivatives based on the quinolin-4(1H)-one scaffold, bicyclic secondary sulfonamides or saccharins were synthesized and evaluated for their SIRT inhibitory effect. Among the evaluated scaffolds, the benzothiadiazine-1,1-dioxide-based compounds showed the highest SIRT2 inhibitory activity. Molecular modeling studies gave insight into the binding mode of the new scaffold-replacement analogues.
- Seifert, Tina,Malo, Marcus,Kokkola, Tarja,Stéen, E. Johanna L.,Meinander, Kristian,Wallén, Erik A.A.,Jarho, Elina M.,Luthman, Kristina
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supporting information
(2019/12/24)
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- N-thioaryl/alkyl o-sulfonylbenzoylimine and preparation method and application thereof
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The invention relates to N-thioaryl/alkyl o-sulfonylbenzoylimine and a preparation method and application thereof. O-sulfonylbenzoylimine is taken as a raw material and reacts with sodium hydride to obtain sodium salt of the o-sulfonylbenzoylimine; the prepared sodium salt of the o-sulfonylbenzoylimine reacts with benzenesulfenyl chloride or alkyl sulfenyl chloride to obtain the N-thioaryl/alkyl o-sulfonylbenzoylimine which can be applied to a thioarylation/alkylation reaction. Compared with the prior art, the preparation method involved in the invention has the advantages that reaction conditions are mild, the chemical yield is high, a new thioaryl/alkyl reagent which is not sensitive to water and air and is relatively high in stability is synthesized, the prepared N-thioaryl/alkyl o-sulfonylbenzoylimine can be used as an electrophilic thioarylation/alkylation reagent with relatively high activity, and a very good application prospect is realized.
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Paragraph 0019; 0034-0035
(2019/10/10)
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- Regioselective C-H bond amination by aminoiodanes
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A new approach for the direct amination of 2-phenylpyridine derivatives using a diphthalimide-iodane and copper triflate has been developed. A series of different 2-phenylpyridine derivatives were aminated with yields up to 88%. Mechanistic investigations indicate that the reaction proceeds via a copper-mediated single electron transfer. This journal is
- Kantak, Abhishek A.,Marchetti, Louis,Deboef, Brenton
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supporting information
p. 3574 - 3577
(2015/03/18)
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- FATTY ACID AMIDE HYDROLASE INHIBITORS
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Disclosed are compounds of formula R-X-Y that may be used to inhibit the action of fatty acid amide hydrolase (FAAH). Inhibition of fatty acid amide hydrolase (FAAH) will slow the normal degradation and inactivation of endogenous cannabinoid ligands by FAAH hydrolysis and allow higher levels of those endogenous cannabinergic ligands to remain present. These higher levels of endocannabinoid ligands provide increased stimulation of the cannabinoid CBl and CB2 receptors and produce physiological effects related to the activation of the cannabinoid receptors. They will also enhance the effects of other exogenous cannabinergic ligands and allow them to produce their effects at lower concentrations as compared to systems in which fatty acid amide hydrolase (FAAH) action is hot inhibited. Thus, a compound that inhibits the inactivation of endogenous cannabinoid ligands by fatty acid amide hydrolase (FAAH) may increase the levels of endocannabinoids and, thus, enhance the activation of cannabinoid receptors. Thus, the compound may not directly modulate the cannabinoid receptors but has the effect of indirectly stimulating the cannabinoid receptors by increasing the levels of endocannabinoid ligands. It may also enhance the effects and duration of action of other exogenous cannabinergic ligands that are administered in order to elicit a cannabinergic response.
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Page/Page column 84-85
(2008/06/13)
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- Synthesis of 1,2-benzisothiazole-1,1-dioxides
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A process is provided for preparing 1,2-benzisothiazole-1,1-dioxides having structure (1): STR1 where R is a C1 -C20 alkyl or aryl radical, the process comprising the steps of: (a) preparing a solution in an anhydrous solvent of a saccharin salt having structure (2): STR2 where Z+ is a metallic cation other than magnesium; and (b) reacting heterogeneously the saccharin salt with an organomagnesium reagent in a relative magnesium to saccharin salt molar ratio of 1:1.
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- Preparation for prevention of emission of mercury from amalgam fillings and method
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A method of preventing or decreasing the emission of mercury vapor in the mouth, from a mercury amalgam filling, comprising contacting the amalgam filling with an oral composition containing sulfur in an amount sufficient to reduce or eliminate the emission of mercury or mercury vapor. The oral composition may be in the form of a toothpaste, chewing gum, mouthwash water, mouth spray, or the like.
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- 4-Aryl-4-piperidinecarbinols
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4-Aryl-4-piperidinecarbinols, for example, STR1 useful as antidepressants and, in some cases, as anorectic agents.
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