- Mild, General, and Regioselective Synthesis of 2-Aminopyridines from Pyridine N -Oxides via N -(2-Pyridyl)pyridinium Salts
-
A synthesis of 2-aminopyridines from pyridine N-oxides via their corresponding N-(2-pyridyl)pyridinium salts has been demonstrated and investigated. The reaction sequence features a highly regioselective conversion of the N-oxide into its pyridinium salt
- Xiong, Hui,Hoye, Adam T.
-
p. 371 - 375
(2022/01/27)
-
- Design, synthesis and biological evaluation of arylpyridin-2-yl guanidine derivatives and cyclic mimetics as novel msk1 inhibitors. An application in an asthma model
-
Mitogen-and Stress-Activated Kinase 1 (MSK1) is a nuclear kinase, taking part in the activation pathway of the pro-inflammatory transcription factor NF-kB and is demonstrating a therapeutic target potential in inflammatory diseases such as asthma, psoriasis and atherosclerosis. To date, few MSK1 inhibitors were reported. In order to identify new MSK1 inhibitors, a screening of a library of low molecular weight compounds was performed, and the results highlighted the 6-phenylpyridin-2-yl guanidine (compound 1a, IC50~18 μM) as a starting hit for structure-activity relationship study. Derivatives, homologues and rigid mimetics of 1a were designed, and all synthesized compounds were evaluated for their inhibitory activity towards MSK1. Among them, the non-cytotoxic 2-aminobenzimidazole 49d was the most potent at inhibiting significantly: (i) MSK1 activity, (ii) the release of IL-6 in inflammatory conditions in vitro (IC50~2 μM) and (iii) the inflammatory cell recruitment to the airways in a mouse model of asthma.
- Bihel, Frédéric,Bollenbach, Maud,Bourguignon, Jean-Jacques,Camelin, Guillaume,Daubeuf, Fran?ois,Frossard, Nelly,Nemska, Simona,Obrecht, Adeline,Rognan, Didier,Schmitt, Martine,Villa, Pascal,Wagner, Patrick
-
-
- UREA DERIVATIVES AS CB1 ALLOSTERIC MODULATORS
-
Heteroaryl and aliphatic analogs of diarylurea-based cannabinoid 1 receptor (CB1 R) allosteric modulators of formula (I) are described. Exemplary analogs can provide improved potencies and pharmacokinetic properties. Methods of using the analogs to treat
- -
-
Page/Page column 61; 62
(2021/01/23)
-
- Synthesis and Pharmacological Evaluation of 1-Phenyl-3-Thiophenylurea Derivatives as Cannabinoid Type-1 Receptor Allosteric Modulators
-
We previously reported diarylurea derivatives as cannabinoid type-1 receptor (CB1) allosteric modulators, which were effective in attenuating cocaine-seeking behavior. Herein, we extended the structure-activity relationships of PSNCBAM-1 (2) at the central phenyl ring directly connected to the urea moiety. Replacement with a thiophene ring led to 11 with improved or comparable potencies in calcium mobilization, [35S]GTPγS binding, and cAMP assays, whereas substitution with nonaromatic rings led to significant attenuation of the modulatory activity. These compounds had no inverse agonism in [35S]GTPγS binding, a characteristic that is often thought to contribute to adverse psychiatric effects. While 11 had good metabolic stability in rat liver microsomes, it showed modest solubility and blood-brain barrier permeability. Compound 11 showed an insignificant attenuation of cocaine seeking behavior in rats, most likely due to its limited CNS penetration, suggesting that pharmacokinetics and distribution play a role in translating the in vitro efficacy to in vivo behavior.
- Nguyen, Thuy,Gamage, Thomas F.,Decker, Ann M.,Barrus, Daniel,Langston, Tiffany L.,Li, Jun-Xu,Thomas, Brian F.,Zhang, Yanan
-
p. 9806 - 9823
(2019/11/11)
-
- METHODS FOR EXTERNAL BASE-FREE SUZUKI COUPLINGS
-
The present disclosure describes a method of coupling a first aromatic compound to a second aromatic compound, the method comprising: (a) preparing a reaction mixture comprising the first aromatic compound, the second aromatic compound, a catalyst and water; the reaction mixture does not contain an external base, the reaction mixture having an initial pH of from 11 to 1; the catalyst having at least one group 10 atom; the first aromatic compound having a halogen, triflate or sulfonate substituent; the second aromatic compound having a boron-containing substituent; wherein, at least one of the first aromatic compound or the second aromatic compound includes one or more heteroatom; and (b) reacting the first aromatic compound and the second aromatic compound in the reaction mixture, the reaction mixture having a final pH following reaction of the first aromatic compound and the second aromatic compound.
- -
-
Paragraph 0035-0036
(2017/07/14)
-
- Identification of the Privileged Position in the Imidazo[1,2-a]pyridine Ring of Phosphonocarboxylates for Development of Rab Geranylgeranyl Transferase (RGGT) Inhibitors
-
Members of the Rab GTPase family are master regulators of vesicle trafficking. When disregulated, they are associated with a number of pathological states. The inhibition of RGGT, an enzyme responsible for post-translational geranylgeranylation of Rab GTPases represents one way to control the activity of these proteins. Because the number of molecules modulating RGGT is limited, we combined molecular modeling with biological assays to ascertain how modifications of phosphonocarboxylates, the first reported RGGT inhibitors, rationally improve understanding of their structure-activity relationship. We have identified the privileged position in the core scaffold of the imidazo[1,2-a]pyridine ring, which can be modified without compromising compounds' potency. Thus modified compounds are micromolar inhibitors of Rab11A prenylation, simultaneously being inactive against Rap1A/Rap1B modification, with the ability to inhibit proliferation of the HeLa cancer cell line. These findings were rationalized by molecular docking, which recognized interaction of phosphonic and carboxylic groups as decisive in phosphonocarboxylate localization in the RGGT binding site.
- Ka?mierczak, Aleksandra,Kusy, Damian,Niinivehmas, Sanna P.,Gmach, Joanna,Joachimiak, ?ukasz,Pentik?inen, Olli T.,Gendaszewska-Darmach, Edyta,B?azewska, Katarzyna M.
-
supporting information
p. 8781 - 8800
(2017/11/15)
-
- Pd-Catalyzed Suzuki coupling reactions of aryl halides containing basic nitrogen centers with arylboronic acids in water in the absence of added base
-
The Pd-catalyzed Suzuki coupling reactions of a series of aryl chlorides and aryl bromides containing basic nitrogen centers with arylboronic acids in water in the absence of added base are reported. The reactions proceed either partially or entirely under acidic conditions. After surveying twenty-two phosphorus ligands, high yields of products were obtained with aryl chlorides only when a bulky ligand, 2-(di-tert-butyl-phosphino)-1-phenyl-1H-pyrrole (cataCXiumPtB) was used. In contrast, aryl bromides produced high yields of products in the absence of both added base and added ligand. In order to explore the Suzuki coupling process entirely under acidic conditions, a series of reactions were conducted in buffered acidic media using several model substrates. 4-Chlorobenzylamine, in the presence of cataCXiumPtB, produced high yields of product at buffered pH 6.0; the yields dropped off precipitously at buffered pH 5.0 and lower. The fall-off in yield was attributed to the decomposition of the Pd-ligand complex due to the protonation of the ligand in the more acidic aqueous media. In contrast, in the absence of an added ligand, 4-amino-2-chloropyridine produced quantitative yields at buffered pH 3.5 and 4.5 while 4-amino-2-bromopyridine produced quantitative yields in a series of buffered media ranging from pH 4.5 to 1.5. These substrates are only partially protonated in acidic media and can behave as active Pd ligands in the Suzuki catalytic cycle.
- Li, Zhao,Gelbaum, Carol,Campbell, Zachary S.,Gould, Paul C.,Fisk, Jason S.,Holden, Bruce,Jaganathan, Arvind,Whiteker, Gregory T.,Pollet, Pamela,Liotta, Charles L.
-
supporting information
p. 15420 - 15432
(2017/12/15)
-
- Aqueous Suzuki Coupling Reactions of Basic Nitrogen-Containing Substrates in the Absence of Added Base and Ligand: Observation of High Yields under Acidic Conditions
-
A series of aqueous heterogeneous Suzuki coupling reactions of substrates containing basic nitrogen centers with phenylboronic acid in the absence of added base and ligand is presented. High yields of products were obtained by employing aryl bromides containing aliphatic 1°, 2°, and 3° amine substituents, and good to high yields were obtained by employing a variety of substituted bromopyridines. In the former series, the pH of the aqueous phase changed from basic to acidic during the course of the reaction, while in the latter series the aqueous phase was on the acidic side of the pH scale throughout the entire course of reaction. A mechanistic interpretation for these observations, which generally preserves the oxo palladium catalytic cycle widely accepted in the literature, is presented.
- Li, Zhao,Gelbaum, Carol,Fisk, Jason S.,Holden, Bruce,Jaganathan, Arvind,Whiteker, Gregory T.,Pollet, Pamela,Liotta, Charles L.
-
p. 8520 - 8529
(2016/09/28)
-
- The synthesis and evaluation of indolylureas as PKCα inhibitors
-
PKCα and PKA have crucial but opposing roles in the regulation of calcium handling within myocytes. Identification of compounds that inhibit PKCα, but not PKA, are potential therapeutic targets for the treatment of heart disease. The synthesis of indolylureas are described, and a compound displaying nanomolar inhibition towards PKCα with significant selectivity over PKA has been identified.
- Djung, Jane F.,Mears, Richard. J.,Montalbetti, Christian A.G.N.,Coulter, Thomas S.,Golebiowski, Adam,Carr, Andrew N.,Barker, Oliver,Greis, Kenneth D.,Zhou, Songtao,Dolan, Elizabeth,Davis, Gregory F.
-
experimental part
p. 2742 - 2750
(2011/06/17)
-
- Facile access to biaryls and 2-acetyl-5-arylbenzofurans via Suzuki coupling in water under thermal and microwave conditions
-
The phosphine-free Suzuki-Miyaura carbon-carbon cross-coupling reactions of activated and deactivated aryl halides and 2-acetyl-5-bromobenzofuran with various aryl-or heteroarylboronic acids were investigated. A benzothiazole-based palladium(II) complex was used as a precatalyst for the reactions under both thermal and microwave conditions in air using water as a solvent. Georg Thieme Verlag Stuttgart - New York.
- Darweesh, Ahmed F.,Shaaban, Mohamed R.,Farag, Ahmad M.,Metz, Peter,Dawood, Kamal M.
-
experimental part
p. 3163 - 3173
(2010/11/04)
-
- ANTHRACENE DERIVATIVE AND ORGANIC ELECTROLUMINESCENT ELEMENT USING THE SAME
-
This invention provides an anthracene derivative, which has a heteroaryl group containing a nitrogen-containing six-membered ring and has a specific structure and comprises an organic thin film layer having a single or multilayer structure including at least a luminescent layer between a cathode and an anode. At least one of the organic thin film layers contains the anthracene derivative either solely or as a component of a mixture. The organic electroluminescent element can emit homogeneous luminscence for a long period of time and has a prolonged service life. The anthracene derivative can realize the above organic electroluminescent element.
- -
-
Page/Page column 54-55
(2008/06/13)
-
- Direct synthesis of hetero-biaryl compounds containing an unprotected NH2 group via Suzuki-Miyaura reaction
-
Hetero-biaryl compounds were prepared via the Suzuki-Miyaura coupling reaction of hetero-aryl moieties containing an unprotected NH2 group and arylboronic acids. D-t-BPF was found to be an efficient ligand for the cross-coupling of NH2/su
- Itoh, Takahiro,Mase, Toshiaki
-
p. 3573 - 3577
(2007/10/03)
-