- Nickel-Catalyzed Reductive Cross-Coupling of N-Acyl and N-Sulfonyl Benzotriazoles with Diverse Nitro Compounds: Rapid Access to Amides and Sulfonamides
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Herein we report a Ni-catalyzed reductive transamidation of conveniently available N-acyl benzotriazoles with alkyl, alkenyl, and aryl nitro compounds, which afforded various amides with good yields and a broad substrate scope. The same catalytic reaction conditions were also applicable for N-sulfonyl benzotriazoles, which could undergo smooth reductive coupling with nitroarenes and nitroalkanes to afford the corresponding sulfonamides.
- Qu, Erdong,Li, Shangzhang,Bai, Jin,Zheng, Yan,Li, Wanfang
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supporting information
p. 58 - 63
(2021/12/27)
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- Hypervalent Iodine Mediated Sulfonamide Synthesis
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A new metal-free sulfonylation reaction is described. The method takes advantage of the Umpolung reactivity and group-transfer properties of iodine(III) compounds, combining hypervalent iodine reagents and sulfinate salts to deliver a clean and mild transfer of sulfonyl groups to amines and anilines. A total of 25 sulfonamides was synthesised in up to 99 % yield, even on gram-scale. The reaction mechanism was investigated by ESI-MS and DFT calculations.
- Poeira, Diogo L.,Macara, Jo?o,Faustino, Hélio,Coelho, Jaime A. S.,Gois, Pedro M. P.,Marques, M. Manuel B.
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supporting information
p. 2695 - 2701
(2019/04/08)
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- ORGANIC REACTIONS CARRIED OUT IN AQUEOUS SOLUTION IN THE PRESENCE OF A HYDROXYALKYL(ALKYL)CELLULOSE OR AN ALKYLCELLULOSE
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The present invention relates to a method of carrying out an organic reaction in aqueous solution in the presence of a hydroxyalkyl(alkyl)cellulose or an alkylcellulose.
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Page/Page column 247; 248
(2017/08/21)
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- Compositions for Treatment of Cystic Fibrosis and Other Chronic Diseases
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The present invention relates to pharmaceutical compositions comprising an inhibitor of epithelial sodium channel activity in combination with at least one ABC Transporter modulator compound of Formula A, Formula B, Formula C, or Formula D. The invention also relates to pharmaceutical formulations thereof, and to methods of using such compositions in the treatment of CFTR mediated diseases, particularly cystic fibrosis using the pharmaceutical combination compositions.
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Paragraph 0451; 1769
(2015/09/22)
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- Indolinyl-thiazole based inhibitors of scavenger receptor-BI (SR-BI)-mediated lipid transport
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A potent class of indolinyl-thiazole based inhibitors of cellular lipid uptake mediated by scavenger receptor, class B, type I (SR-BI) was identified via a high-throughput screen of the National Institutes of Health Molecular Libraries Small Molecule Repo
- Dockendorff, Chris,Faloon, Patrick W.,Yu, Miao,Youngsaye, Willmen,Penman, Marsha,Nieland, Thomas J. F.,Nag, Partha P.,Lewis, Timothy A.,Pu, Jun,Bennion, Melissa,Negri, Joseph,Paterson, Conor,Lam, Garrett,Dandapani, Sivaraman,Perez, José R.,Munoz, Benito,Palmer, Michelle A.,Schreiber, Stuart L.,Krieger, Monty
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supporting information
p. 375 - 380
(2015/04/27)
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- Metal-free direct construction of sulfonamides via iodine- mediated coupling reaction of sodium sulfinates and amines at room temperature
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A simple, practical, and metal-free protocol has been developed for the synthesis of sulfonamides from sodium sulfinates and various amines through an iodine-mediated SN bond formation reaction at room temperature. This green reaction is cost-effective, operationally straightforward, and especially proceeds under very mild conditions to afford the target products in good to excellent yields (up to 98%).
- Wei, Wei,Liu, Chunli,Yang, Daoshan,Wen, Jiangwei,You, Jinmao,Wang, Hua
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supporting information
p. 987 - 992
(2015/03/30)
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- Discovery of N -(2,4-Di- tert -butyl-5-hydroxyphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide (VX-770, Ivacaftor), a potent and orally bioavailable CFTR potentiator
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Quinolinone-3-carboxamide 1, a novel CFTR potentiator, was discovered using high-throughput screening in NIH-3T3 cells expressing the F508del-CFTR mutation. Extensive medicinal chemistry and iterative structure-activity relationship (SAR) studies to evaluate potency, selectivity, and pharmacokinetic properties resulted in the identification of N-(2,4-di-tert-butyl-5-hydroxyphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide (VX-770, 48, ivacaftor), an investigational drug candidate approved by the FDA for the treatment of CF patients 6 years of age and older carrying the G551D mutation.
- Hadida, Sabine,Van Goor, Fredrick,Zhou, Jinglan,Arumugam, Vijayalaksmi,McCartney, Jason,Hazlewood, Anna,Decker, Caroline,Negulescu, Paul,Grootenhuis, Peter D. J.
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supporting information
p. 9776 - 9795
(2015/01/16)
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- THIAZOLE-BASED INHIBITORS OF SCAVENGER RECEPTOR BI
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This application describes compounds and methods that can inhibit Scavenger receptor class B, type I (SR-BI) activity, which compounds and methods can used, for example, to mediate high-density lipoprotein (HDL) lipid uptake and treat hepatitis C viral in
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Page/Page column 21; 42; 43
(2014/05/07)
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- MODULATORS OF ATP-BINDING CASSETTE TRANSPORTERS
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The present invention relates to modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator, compositions thereof, and methods therewith. The present invention also relates to methods of treating ABC transporter mediated diseases using such modulators.
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Page/Page column 75
(2012/12/14)
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- Sulfonamides for the Modulation of PKM2
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The invention relates to sulfonamide compounds and methods for activating PKM2. The compounds and methods are useful in treating or preventing a disease or disorder selected from cancer, cell proliferative disorder, inflammatory disorder, metabolic disorder, and immune system disorder.
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Page/Page column 54
(2012/05/07)
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- 1-(sulfonyl)-5-(arylsulfonyl)indoline as activators of the tumor cell specific M2 isoform of pyruvate kinase
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Cancer cells preferentially use glycolysis rather than oxidative phosphorylation for their rapid growth. They consume large amount of glucose to produce lactate even when oxygen is abundant, a phenomenon known as the Warburg effect. This metabolic change originates from a shift in the expression of alternative spliced isoforms of the glycolytic enzyme pyruvate kinase (PK), from PKM1 to PKM2. While PKM1 is constitutively active, PKM2 is switched from an inactive dimer form to an active tetramer form by small molecule activators. The prevalence of PKM2 in cancer cells relative to the prevalence of PKM1 in many normal cells, suggests a therapeutic strategy whereby activation of PKM2 may counter the abnormal cellular metabolism in cancer cells, and consequently decreased cellular proliferation. Herein we describe the discovery and optimization of a series of PKM2 activators derived from the 2-((2,3-dihydrobenzo[b][1,4] dioxin-6-yl)thio)-1-(2-methyl-1-(methylsulfonyl) indolin-5-yl) ethanone scaffold. The synthesis, SAR analysis, enzyme active site docking, enzymatic reaction kinetics, selectivity and pharmaceutical properties are discussed.
- Yacovan, Avihai,Ozeri, Rachel,Kehat, Tzofit,Mirilashvili, Sima,Sherman, Daniel,Aizikovich, Alex,Shitrit, Alina,Ben-Zeev, Efrat,Schutz, Nili,Bohana-Kashtan, Osnat,Konson, Alexander,Behar, Vered,Becker, Oren M.
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supporting information
p. 6460 - 6468
(2012/11/07)
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- Mepyramine-JNJ7777120-hybrid compounds show high affinity to hH 1R, but low affinity to hH4R
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In literature, a synergism between histamine H1 and H 4 receptor is discussed. Furthermore, it was shown, that the combined application of mepyramine, a H1 antagonist and JNJ7777120, a H 4 receptor ligand leads to a synergistic effect in the acute murine asthma model. Thus, the aim of this study was to develop new hybrid ligands, containing one H1 and one H4 pharmacophor, connected by an appropriate spacer, in order to address both, H1R and H 4R. Within this study, we synthesized nine hybrid compounds, which were pharmacologically characterized at hH1R and hH4R. The new compounds revealed (high) affinity to hH1R, but showed only low affinity to hH4R. Additionally, we performed molecular dynamic studies for some selected compounds at hH1R, in order to obtain information about the binding mode of these compounds on molecular level.
- Wagner, Eva,Wittmann, Hans-Joachim,Elz, Sigurd,Strasser, Andrea
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supporting information; experimental part
p. 6274 - 6280
(2011/11/29)
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- COMPOSITIONS FOR TREATMENT OF CYSTIC FIBROSIS AND OTHER CHRONIC DISEASES
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The present invention relates to pharmaceutical compositions comprising an inhibitor of epithelial sodium channel activity in combination with at least one ABC Transporter modulator compound of Formula A, Formula B, Formula C, or Formula D. The invention also relates to pharmaceutical formulations thereof, and to methods of using such compositions in the treatment of CFTR mediated diseases, particularly cystic fibrosis using the pharmaceutical combination compositions.
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- Rearrangement of indolinesulfonamides to sulfones using polyphosphoric acid (PPA)
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Unlike other N-alkylsulfonanilides, indolinesulfonamides hydrolyze in 98% sulfuric acid. Recent work in this laboratory has shown that rearrangement can be achieved by using polyphosphoric acid. A series of substituted indolinesulfonamides has been prepar
- Raszka, Brian,McKee, James,Zanger, Murray
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experimental part
p. 1837 - 1846
(2010/07/05)
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- Pd(II)-catalyzed amination of C-H bonds using single-electron or two-electron oxidants
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(Chemical Equation Presented) Pd(II)-catalyzed intramolecular amination of arenes is developed using either a one- or two-electron oxidant. The reaction protocol tolerates a wide range of deactivating groups including acetyl, cyano, and nitro groups. This catalytic reaction allows expedient syntheses of broadly useful substituted indolines or indoles.
- Mei, Tian-Sheng,Wang, Xisheng,Yu, Jin-Quan
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supporting information; experimental part
p. 10806 - 10807
(2009/12/04)
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- Modulators of ATP-binding cassette transporters
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Compounds of the present invention and pharmaceutically acceptable compositions thereof, are useful as modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator (“CFTR”). The present invention also relates to methods of treating ABC transporter mediated diseases using compounds of the present invention.
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Page/Page column 143-144
(2008/06/13)
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- Synthesis and biological evaluation of 5-[(aryl)(1H-imidazol-1-yl)methyl]- 1H-indoles: Potent and selective aromatase inhibitors
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The synthesis and the aromatase (CYP19) inhibitory activity of 5-[(aryl)(imidazol-1-yl)methyl]-1H-indoles were reported. Among the tested racemate compounds, 5-[(4-chlorophenyl)(1H-imidazol-1-yl)methyl]-1H-indole 8b emerged as a potent CYP19 inhibitor (IC
- Leze, Marie-Pierre,Le Borgne, Marc,Pinson, Patricia,Palusczak, Anja,Duflos, Muriel,Le Baut, Guillaume,Hartmann, Rolf W.
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p. 1134 - 1137
(2007/10/03)
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- THE REDUCTION OF N-(PHENYLSULFONYL)INDOLES WITH SODIUM CYANOBOROHYDRIDE IN TRIFLUOROACETIC ACID
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The reduction of N-(phenylsulfonyl)indoles to the corresponding N-(phenylsulfonyl)indolines can be accomplished with good to excellent yields using cyanoborohydride (NaCNBH3) in trifluoroacetic acid (TFA).
- Ketcha, Daniel M.,Lieurance, Brett A.
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p. 6833 - 6836
(2007/10/02)
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