- Nucleofugality hierarchy, in the aminolysis reaction of 4-cyanophenyl 4-nitrophenyl carbonate and thionocarbonate. Experimental and theoretical study
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Nucleophilic substitution reactions of the title compounds have been investigated with a series of secondary alicyclic amines in several solvents. The solvent, amine, and electrophilic group effects on kinetics, mechanism and nucleofugality hierarchy are discussed from experimental and theoretical studies. These studies show the mechanistic dependence on the solvent polarity; the theoretical results indicate that the relative polarization of the reactive centres (CO and CS) and the stabilization of the nucleofuges are the main factors in the control of the product distribution.
- Aliaga, Margarita E.,Cornejo, Patricio,Montecinos, Rodrigo,Pavez, Paulina,Santos, José G.
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p. 11495 - 11505
(2021/07/12)
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- Nickel-Catalyzed Decarboxylation of Aryl Carbamates for Converting Phenols into Aromatic Amines
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Herein, we describe a new catalytic approach to accessing aromatic amines from an abundant feedstock, namely phenols. The most reliable catalytic method for converting phenols to aromatic amines uses an activating group, such as a trifluoromethane sulfonyl group. However, this activating group is eliminated as a leaving group during the amination process, resulting in significant waste. Our nickel-catalyzed decarboxylation reaction of aryl carbamates forms aromatic amines with carbon dioxide as the only byproduct. As this amination proceeds in the absence of free amines, a range of functionalities, including a formyl group, are compatible. A bisphosphine ligand immobilized on a polystyrene support (PS-DPPBz) is key to the success of this reaction, generating a catalytic species that is significantly more active than simple nonsupported variants.
- Nishizawa, Akihiro,Takahira, Tsuyoshi,Yasui, Kosuke,Fujimoto, Hayato,Iwai, Tomohiro,Sawamura, Masaya,Chatani, Naoto,Tobisu, Mamoru
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supporting information
p. 7261 - 7265
(2019/05/16)
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- SUBSTITUTED HETEROARYL COMPOUNDS AND METHODS OF USE
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The present invention provides novel heteroaryl compounds, pharmaceutical acceptable salts and formulations thereof. They are useful in preventing, managing, treating or lessening the severity of a protein kinase-mediated disease. The invention also provides pharmaceutically acceptable compositions comprising such compounds and methods of using the compositions in the treatment of protein kinase-mediated disease.
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Paragraph 0456
(2017/03/28)
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- Substituted heteroaryl compounds and composition thereof, and applicaitons of compounds and composition
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The invention provides substituted heteroaryl compounds and a composition thereof, and applicaitons of the compounds and the composition. The compounds are compounds represented by the formula (I) or the formula (II) or stereoisomers, tautomers, nitrogen oxides, solvates, metabolites, pharmaceutically acceptable salts or prodrugs of the compounds represented by the formula (I) or the formula (II). The invention also provides the pharmaceutical composition comprising the compounds; the compounds and the pharmaceutical composition can adjust the activity of protein kinase, and are used for prevention, processing, treatment and remission of diseases or disorders mediated by the protein kinase.
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Paragraph 0882; 0883; 0884; 0885
(2017/07/31)
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- Structure-reactivity correlations in the aminolysis of aryl chloroformates
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The reactions of a series of secondary alicyclic amines with 4-methylphenyl and 4-methoxyphenyl chloroformates are subjected to a kinetic investigation in water, at 25.0°C, ionic strength 0.2 M (KCI). Under amine excess, pseudo-first-order rate coefficients (kobs) are found for all reactions. Plots of kobs vs [NH] (NH is the free amine) are linear, with the slope (kN) pH independent, except the reactions of l-(2-hydroxyethyl)piperazine with both substrates at pH 6.2-7.3. The Broensted-type plots for the kN values for the aminolysis of both chloroformates are linear, with slopes ca. 0.3, which is consistent with rate-determining formation of a zwitterionic tetrahedral intermediate (T±). With the PKa and log kN data for the present reactions, together with those for the same aminolysis of phenyl and 4-nitrophenyl chloroformates, two dual parametric equations are found for log kN as a function of pKa of the nucleophile, Hammett sigma of the "nonleaving" group, and pKa of the "nonleaving" group, with coefficients βN = 0.3, ρnlg = 0.7, and βnlg = -0.2, respectively.
- Castro, Enrique A.,Ruiz, Mara G.,Santos, Jos G.
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p. 281 - 287
(2007/10/03)
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- Inactivation of the human papillomavirus-16 E6 oncoprotein by organic disulfides
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We are investigating compounds that could be useful in the treatment of neoplastic lesions of the cervix by acting on the oncoprotein E6 of human papillomavirus-16. The E6 protein contains two potential zinc-binding domains that are required for most of its functions. We have published tests that measure (i) the release of zinc ions after chemical alteration of the cysteine groups of these zinc-binding domains (TSQ assay), (ii) the interaction of E6 with the cellular proteins E6AP and E6BP (BIACORE assay), and (iii) the viability of tumor cell lines that require the continuous expression of HPV oncoproteins (WST1 assay). Based on these tests, we identified 4,4'-dithiodimorpholine as a potential lead compound. In this study we examined whether the dithiobisamine moiety of 4,4'-dithiodimorpholine may be an important molecular prerequisite for further drug development in this system. We have evaluated 59 new substances including organic disulfides and those containing the dithiobisamine moiety, as well as structural analogues. The compounds with significant reactivity in all three assays were observed only for dithiobisamine derivatives with saturated cyclic amines and aryl substituted piperazines. The identity of these substances suggests that the N-S-S-N moiety is necessary but not sufficient for reactivity in our assays, and that dithiobisamine based substances are useful as lead compounds that target the cysteine groups of HPV-16 E6 zinc fingers. Copyright (C) 2000 Elsevier Science Ltd.
- Beerheide, Walter,Sim, Mui Mui,Tan, Yee-Joo,Bernard, Hans-Ulrich,Ting, Anthony E
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p. 2549 - 2560
(2007/10/03)
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- Kinetics and mechanism of the aminolysis of phenyl and 4-nitrophenyl chloroformates in aqueous solution
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The reactions of secondary alicyclic amines with phenyl and 4- nitrophenyl chloroformates (PClF and NPClF, respectively) are subjected to a kinetic investigation in aqueous solution, 25.0 °C, ionic strength 0.2 (KCl). The reactions are followed spectropho
- Castro, Enrique A.,Ruiz, Maria G.,Salinas, Sandra,Santos, Jose G.
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p. 4817 - 4820
(2007/10/03)
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