- A Scaffold-Hopping Strategy toward the Identification of Inhibitors of Cyclin G Associated Kinase
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We recently reported the discovery of isothiazolo[4,3-b]pyridine-based inhibitors of cyclin G associated kinase (GAK) displaying low nanomolar binding affinity for GAK and demonstrating broad-spectrum antiviral activity. To come up with novel core structures that act as GAK inhibitors, a scaffold-hopping approach was applied starting from two different isothiazolo[4,3-b]pyridines. In total, 13 novel 5,6- and 6,6-fused bicyclic heteroaromatic scaffolds were synthesized. Four of them displayed GAK affinity with Kd values in the low micromolar range that can serve as chemical starting points for the discovery of GAK inhibitors based on a different scaffold.
- Wouters, Randy,Tian, Junjun,Herdewijn, Piet,De Jonghe, Steven
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p. 237 - 254
(2019/01/08)
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- N-Unsubstituted thienoisoindigos: preparation, molecular packing and ambipolar organic field-effect transistors
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N-Unsubstituted thienoisoindigo (TIIG) and its diphenyl derivative (dph-TIIG) are synthesized by using a tert-butoxy carbonyl (t-Boc) group as a protecting group. TIIG has a stacking structure analogous to isoindigo, and dph-TIIG is a hybrid of brickwork
- Yoo, Dongho,Hasegawa, Tsukasa,Ashizawa, Minoru,Kawamoto, Tadashi,Masunaga, Hiroyasu,Hikima, Takaaki,Matsumoto, Hidetoshi,Mori, Takehiko
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supporting information
p. 2509 - 2512
(2017/03/17)
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- Efficient and Mild Ullmann-Type N-Arylation of Amides, Carbamates, and Azoles in Water
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A simple, sustainable, efficient, mild, and low-cost protocol was developed for d-glucose-assisted Cu-catalyzed Ullmann reactions in water for amides, carbamates, and nitrogen-containing heterocycles. The reaction was compatible with diverse aryl/heteroaryl iodides, giving highly substituted pyridine, indole, or indazole rings. This method offers an attractive alternative to existing protocols, because the reaction proceeds in aqueous media, occurs at or near ambient temperature, and provides the N-arylated products in good to high yields.
- Bollenbach, Maud,Aquino, Pedro G. V.,de Araújo-Júnior, Jo?o Xavier,Bourguignon, Jean-Jacques,Bihel, Frédéric,Salomé, Christophe,Wagner, Patrick,Schmitt, Martine
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supporting information
p. 13676 - 13683
(2017/10/10)
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- PYRROLOTRIAZINE INHIBITORS OF IRAK4 ACTIVITY
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The present invention relates to pyrrolotriazine inhibitors of IRAK4 of formula (I) and provides compositions comprising such inhibitors, as well as methods therewith for treating IRAK4-mediated or -associated conditions or diseases.
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Page/Page column 40
(2016/09/26)
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- PYRAZOLOPYRIMIDINE INHIBITORS OF IRAK4 ACTIVITY
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The present invention relates to pyrazolopyrimidine inhibitors of IRAK4 of formula (I) and provides compositions comprising such inhibitors, as well as methods therewith for treating IRAK4-mediated or -associated conditions or diseases.
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Page/Page column 61
(2016/09/26)
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- THIENOPYRAZINE INHIBITORS OF IRAK4 ACTIVITY
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The present invention relates to thienopyrazine inhibitors of IRAK4 of formula (I) and provides compositions comprising such inhibitors, as well as methods therewith for treating IRAK4-mediated or -associated conditions or diseases.
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Page/Page column 34; 35
(2016/09/26)
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- PYRROLOPYRIDAZINE INHIBITORS OF IRAK4 ACTIVITY
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The present invention relates to pyrrolopyridazine inhibitors of IRAK4 of formula (I) and provides compositions comprising such inhibitors, as well as methods therewith for treating IRAK4-mediated or -associated conditions or diseases.
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Page/Page column 38
(2016/09/26)
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- Substituted 1,2,3,4-tetrahydrobenzo[C][2,7] naphthyridines and derivatives thereof as kinase inhibitors
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The present invention relates to organic molecules capable of modulating tyrosine kinase signal transduction in order to regulate, modulate and/or inhibit abnormal cell proliferation.
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Page/Page column 45-56
(2016/03/06)
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- Ligandless copper-catalyzed coupling of heteroaryl bromides with gaseous ammonia
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A range of different N- and S-containing heterocyclic bromides can be efficiently coupled with gaseous ammonia in the presence of copper(II) acetylacetonate [Cu(acac)2] as catalyst and in the absence of additional ligands. Unstable aminothiophenes and aminobenzothiophenes can be further reacted in situ to afford functionalized derivatives. Copyright
- Fantasia, Serena,Windisch, Johannes,Scalone, Michelangelo
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supporting information
p. 627 - 631
(2013/04/11)
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- Palladium-catalyzed amidation of aryl halides using 2-dialkylphosphino- 2′-alkoxyl-1,1′-binaphthyl as ligands
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Palladium-catalyzed intermolecular C-N bond-forming reactions between aryl halides and amides are described using 2-dialkylphosphino-2′-alkoxyl-1, 1′-binaphthyl, which is both bulky and electron-rich, as the ligand. A variety of amides, including aliphatic and aromatic primary amides, lactams, and carbamates, were viable substrates for the amidation, which exhibited good functional group compatibility. By tuning the substituents at the 2,2′-position of 1,1′-binaphthyl of the ligand, the palladium-catalyzed amidation of bulky aryl halides was realized and this coupling reaction was used to synthesize 2-amino-2′-methoxy-1,1′- binaphthyl in high yield.
- Ma, Fangfang,Xie, Xiaomin,Zhang, Lei,Peng, Zhiyong,Ding, Lina,Fu, Lei,Zhang, Zhaoguo
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experimental part
p. 5279 - 5285
(2012/08/07)
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- NOVEL ANTIMALARIA AGENT CONTAINING HETEROCYCLIC COMPOUND
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Disclosed is an antimalarial agent containing a compound represented by the formula: [wherein A1 represents a 3-pyridyl group that may have a substituent, a 6-quinolyl group that may have a substituent, or the like; X1 represents a group represented by the formula -C(=O)-NH- or the like; E represents a furyl group, a thienyl group or a phenyl group; with the proviso that A1 may have one to three substituents, and E has one of two substituents] or a salt thereof or hydrates thereof.
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Page/Page column 66
(2008/06/13)
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- Structure-activity relationships in the binding of chemically derivatized CD4 to gp120 from human immunodeficiency virus
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The first step in HIV infection is the binding of the envelope glycoprotein gp120 to the host cell receptor CD4. An interfacial "Phe43 cavity" in gp120, adjacent to residue Phe43 of gp120-bound CD4, has been suggested as a potential target for therapeutic intervention. We designed a CD4 mutant (D1D2F43C) for site-specific coupling of compounds for screening against the cavity. Altogether, 81 cysteine-reactive compounds were designed, synthesized, and tested. Eight derivatives exceeded the affinity of native D1D2 for gp120. Structure-activity relationships (SAR) for derivatized CD4 binding to gp120 revealed significant plasticity of the Phe43 cavity and a narrow entrance. The primary contacts for compound recognition inside the cavity were found to be van der Waals interactions, whereas hydrophilic interactions were detected in the entrance. This first SAR on ligand binding to an interior cavity of gp120 may provide a starting point for structure-based assembly of small molecules targeting gp120-CD4 interaction.
- Xie, Hui,Ng, Danny,Savinov, Sergey N.,Dey, Barna,Kwong, Peter D.,Wyatt, Richard,Smith III, Amos B.,Hendrickson, Wayne A.
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p. 4898 - 4908
(2008/03/11)
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- AMPA RECEPTOR POTENTIATORS
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The present invention relates to AMPA receptor potentiators of Formula I: formulations comprising them, methods for their use, and intermediates useful for their preparation.
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Page/Page column 4
(2010/11/25)
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- NOVEL ANTIFUNGAL AGENT COMPRISING HETEROCYCLIC COMPOUND
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The present invention provides an antifungal agent represented by the formula: [wherein A1 represents a 3-pyridyl group which may have a substituent, a quinolyl group which may have a substituent, or the like; X1 represents a group represented by the formula -NH-C(=O)-, a group represented by the formula -C(=O)-NH-, or the like; E represents a furyl group, a thienyl group, a pyrrolyl group, a phenyl group, a pyridyl group, a tetrazolyl group, a thiazolyl group or a pyrazolyl group; with the proviso that A1 may have 1 to 3 substituents, and E has one or two substituents].
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Page/Page column 74
(2010/11/08)
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- Thienoisoquinoline-phenylsulfonamides and their use as ER-NFkappaB inhibitors
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This invention provides estrogen receptor modulators having the structure: wherein R1 to R7 are as defined in the specification; or a pharmaceutically acceptable salt thereof.
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Page/Page column 7; 11; 12
(2008/06/13)
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- Novel thienopyrrole glycogen phosphorylase inhibitors: Synthesis, in vitro SAR and crystallographic studies
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Two series of novel thienopyrrole inhibitors of recombinant human liver glycogen phosphorylase a (GPa) which are effective in reducing glucose output from rat hepatocytes are described. Representative compounds have been shown to bind at the dimer interface site of the rabbit muscle enzyme by X-ray crystallography.
- Whittamore, Paul R.O.,Addie, Matthew S.,Bennett, Stuart N.L.,Birch, Alan M.,Butters, Michael,Godfrey, Linda,Kenny, Peter W.,Morley, Andrew D.,Murray, Paul M.,Oikonomakos, Nikos G.,Otterbein, Ludovic R.,Pannifer, Andrew D.,Parker, Jeremy S.,Readman, Kristy,Siedlecki, Pawel S.,Schofield, Paul,Stocker, Andy,Taylor, Melvyn J.,Townsend, Linda A.,Whalley, David P.,Whitehouse, Jennifer
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p. 5567 - 5571
(2007/10/03)
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- Copper-catalyzed amidations of bromo substituted furans and thiophenes
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The C-N cross-coupling reaction between aromatic halides and amides has now been applied to 2- and 3-substituted bromofurans and bromothiophenes. Catalytic CuI in the presence of N,N′-dimethylethylenediamine as a ligand and K3PO4 or K2CO3 as the base furnished 2- and 3-substituted amidofurans and thiophenes ranging from 11 to 99% depending on the particular amide source used.
- Crawford, Kenneth R,Padwa, Albert
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p. 7365 - 7368
(2007/10/03)
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