33538-10-2Relevant articles and documents
Silver-Catalyzed Minisci Reactions Using Selectfluor as a Mild Oxidant
Galloway, Jordan D.,Mai, Duy N.,Baxter, Ryan D.
supporting information, p. 5772 - 5775 (2017/11/10)
A new method for silver-catalyzed Minisci reactions using Selectfluor as a mild oxidant is reported. Heteroarenes and quinones both participate in radical C-H alkylation and arylation from a variety of carboxylic and boronic acid radical precursors. Several oxidatively sensitive and highly reactive radical species are successful, providing structures that are challenging to access by other means.
C?H Cyanation of 6-Ring N-Containing Heteroaromatics
Elbert, Bryony L.,Farley, Alistair J. M.,Gorman, Timothy W.,Johnson, Tarn C.,Genicot, Christophe,Lallemand, Bénédicte,Pasau, Patrick,Flasz, Jakub,Castro, José L.,MacCoss, Malcolm,Paton, Robert S.,Schofield, Christopher J.,Smith, Martin D.,Willis, Michael C.,Dixon, Darren J.
supporting information, p. 14733 - 14737 (2017/10/07)
Heteroaromatic nitriles are important compounds in drug discovery, both for their prevalence in the clinic and due to the diverse range of transformations they can undergo. As such, efficient and reliable methods to access them have the potential for far-reaching impact across synthetic chemistry and the biomedical sciences. Herein, we report an approach to heteroaromatic C?H cyanation through triflic anhydride activation, nucleophilic addition of cyanide, followed by elimination of trifluoromethanesulfinate to regenerate the cyanated heteroaromatic ring. This one-pot protocol is simple to perform, is applicable to a broad range of decorated 6-ring N-containing heterocycles, and has been shown to be suitable for late-stage functionalization of complex drug-like architectures.
Unprotected Amino Acids as Stable Radical Precursors for Heterocycle C-H Functionalization
Mai, Duy N.,Baxter, Ryan D.
supporting information, p. 3738 - 3741 (2016/08/16)
An efficient and general method for the C-H alkylation of heteroarenes using unprotected amino acids as stable alkyl radical precursors is reported. This one-pot procedure is performed open to air under aqueous conditions and is effective for several natural and unnatural amino acids. Heterocycles of varying structure are suitably functionalized, and reactivity trends reflect the nucleophilic character of the radical species generated.
Dioxygen-Mediated Decarbonylative C-H Alkylation of Heteroaromatic Bases with Aldehydes
Paul, Subhasis,Guin, Joyram
supporting information, p. 17618 - 17622 (2015/12/05)
An operationally simple and economical method for the direct alkylation of heteroaromatic bases employing readily available aldehydes as alkyl radical precursors and molecular oxygen as a reagent is presented. This simple transformation demonstrates a broad substrate scope with respect to aldehydes and nitrogen heterocycles, enabling the introduction of several medicinally important yet challenging alkyl moieties, such as ethyl, isopropyl, tert-butyl, and cyclohexyl to the different classes of heterocyclic bases in good to excellent yields. A simple method for the direct alkylation of heteroaromatic bases with aldehydes as inexpensive alkyl radical precursors and molecular oxygen as a reagent is presented. This transformation demonstrates a broad substrate scope with respect to aldehydes and nitrogen heterocycles, enabling the introduction of various alkyl moieties to heterocyclic bases (>40 examples) in good to excellent yields.
P2X4 RECEPTOR MODULATING COMPOUNDS
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Paragraph 00244, (2015/06/25)
Provided herein are P2X4 receptor modulating compounds, methods of their synthesis, pharmaceutical compositions comprising the compounds, and methods of their use. The compounds provided herein are useful for the treatment, prevention, and/or management of various disorders, including but not limited to, chronic pain, neuropathy, inflammatory diseases and central nervous system disorders.
Discovery of an N-(2-aminopyridin-4-ylmethyl)nicotinamide derivative: A potent and orally bioavailable NCX inhibitor
Kuramochi, Takahiro,Kakefuda, Akio,Yamada, Hiroyoshi,Tsukamoto, Issei,Taguchi, Taku,Sakamoto, Shuichi
, p. 4022 - 4036 (2007/10/03)
Ca2+ overload in myocardial cells is responsible for arrhythmia. Sodium-calcium exchanger (NCX) inhibitors are more effective than sodium-hydrogen exchanger (NHE) inhibitors with regard to modulation of Ca 2+ overload, because NCX inhibitors can directly inhibit the influx of Ca2+ into cells. NCX is an attractive target for the treatment of heart failure and ischemia-reperfusion. We have designed and synthesized a series of N-(2-aminopyridin-4-ylmethyl)nicotinamide derivatives, based on compound 5. We have discovered a novel NCX inhibitor (23h) with an IC 50 value of 0.12 μM against reverse NCX. The inhibitory activities of our NCX inhibitors against cytochrome P450 were also evaluated. The effects on heart failure and the pharmacokinetic profile of compound 23h are discussed.
New General Processes of Homolytic Alkylation of Heteroaromatic Bases by t-BuOOH or (t-BuO)2 and Alkyl Iodides
Fontana, Francesca,Minisci, Francesco,Barbosa, Maria Claudia Nogueira,Vismara, Elena
, p. 995 - 999 (2007/10/02)
New general, selective processes of homolytic alkylation of protonated heteroaromatic bases have been developed using alkyl iodides and t-BuOOH or (t-BuO)2 as sources of alkyl radicals.Both processes are based on the generation of methyl radical from the peroxides, and on iodine abstraction from the alkyl iodide by the methyl radical.The selective processes are the result of combined enthalpic and polar effects.The enthalpic factor governs the equilibrium of iodine abstraction, whereas the polar effect governs the reactivity of the alkyl radicals with the protonated heteroaromatic ring.A redox chain is operative with t-BuOOH and an unusual free-radical chain process is involved with (t-BuO)2.Both chains are particularly effective because of the electron-transfer oxidation of the pyridyl radical intermediate, the ionization potential of which (5.4-6.0 eV) is close to that of lithium (5.39 eV) or sodium (5.14 eV).
Polar Effects in Free-Radical Reactions. Rate Constants in Phenylation and New Methods of Selective Alkylation of Heteroaromatic Bases
Minisci, Francesco,Vismara, Elena,Fontana, Francesca,Morini, Giampiero,Serravalle, Marco,Giordano, Claudio
, p. 4411 - 4416 (2007/10/02)
The rate constants for the addition of the phenyl radical to protonated and unprotonated 4-substituted pyridines have been determined by competition with chlorine abstraction from CCl4.The constants range from 2 * 105 to 6 * 106 M-1 s-1 depending on the substituent and on the degree of protonation.The phenyl radical shows a clear-cut nucleophilic character.On the basis of these rate constants, the use of phenyl radical from diazonium salt or benzoyl peroxide to generate alkyl radicals by iodine or hydrogen abstraction has been developed as a general procedure for the alkylation of heteroaromatic bases.This reaction is characterized by high yields and selectivities.
A NEW GENERAL METHOD OF HOMOLYTIC ALKYLATION OF PROTONATED HETEROAROMATIC BASES
Castaldi, Graziano,Minisci, Francesko,Tortelli, Vito,Vismara, Elena
, p. 3897 - 3900 (2007/10/02)
Alkyl iodides and benzoyl peroxides provide a new general method of homolytic alkylation of protonated heteroaromatic bases.Yields are good and the substitution is selective in the positions ortho and para to the heteroatom.
