- Design and synthesis of 3′-(prop-2-yn-1-yloxy)-biphenyl substituted cyclic acylguanidine compounds as BACE1 inhibitors
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Based on the lead compounds 1 and 2, a series of novel BACE1 inhibitors were designed and synthesized, among which compound 9h exhibited a 60 fold improvement in potency over the lead compound 1. This represents a good lead for the discovery of more promi
- Liu, Jia-Kuo,Gu, Wei,Cheng, Xiao-Rui,Cheng, Jun-Ping,Nie, Ai-Hua,Zhou, Wen-Xia
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Read Online
- A threonine turnstile defines a dynamic amphiphilic binding motif in the AAA ATPase p97 allosteric binding site
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The turnstile motion of two neighboring threonines sets up a dynamic side chain interplay that can accommodate both polar and apolar ligands in a small molecule allosteric protein binding site. A computational model based on SAR data and both X-ray and cr
- Burnett, James C.,Lim, Chaemin,Peyser, Brian D.,Samankumara, Lalith P.,Kovaliov, Marina,Colombo, Raffaele,Bulfer, Stacie L.,LaPorte, Matthew G.,Hermone, Ann R.,McGrath, Connor F.,Arkin, Michelle R.,Gussio, Rick,Huryn, Donna M.,Wipf, Peter
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Read Online
- (3-(1H-1,2,3-triazole)phenyl)phosphoric acid derivative as well as preparation method and application thereof
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The invention relates to the technical field of medicinal chemistry, and discloses a (3-(1H-1,2,3-triazole)phenyl)phosphoric acid derivative derivative as shown in a formula X which is described in the specification. The derivative has good and broad-spec
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Paragraph 0147
(2021/08/07)
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- COMPOUND FOR ORGANIC OPTOELECTRONIC DEVICE, ORGANIC OPTOELECTRONIC DEVICE AND DISPLAY APPARATUS
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The present invention relates to a compound for an organic optoelectronic device represented by chemical formula 1, an organic optoelectronic device employing the same and a display device apparatus. The details of chemical formula 1 are as defined in the specification.
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Paragraph 0159; 0160
(2018/12/11)
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- Catalytic Activation of Trimethylsilylacetylenes: A One-Pot Route to Unsymmetrical Acetylenes and Heterocycles
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For the synthesis of unsymmetrical acetylenes, a Sonogashira coupling-deprotection-Sonogashira coupling reaction sequence is often used. Removal of protecting groups requires harsh conditions or an excess of difficult to handle and expensive reagents. Herein, we disclose a novel catalytic method for the selective deprotection of trimethylsilylacetylenes in Sonogashira reaction. The reagent hexafluorosilicic acid, an inexpensive nontoxic compound, was used to promote the selective desilylation. This method enables the efficient synthesis of unsymmetric acetylenes with other silylated functional groups present. Further possibilities of the method were explored by synthesis of heterocycles.
- Lasányi, Dániel,Mészáros, ádám,Novák, Zoltán,Tolnai, Gergely L.
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p. 8281 - 8291
(2018/06/11)
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- Enantioselective synthesis of β-fluoro-β-aryl-α-aminopentenamides by organocatalytic [2,3]-sigmatropic rearrangement
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The tetramisole-promoted catalytic enantioselective [2,3]-sigmatropic rearrangement of quaternary ammonium salts bearing a (Z)-3-fluoro-3-arylprop-2-ene group generates, after addition of benzylamine, a range of β-fluoro-β-aryl-α-aminopentenamides containing a stereogenic tertiary fluorine substituent. Cyclic and acyclic nitrogen substituents as well as various aromatic substituents are tolerated, giving the β-fluoro-β-aryl-α-aminopentenamide products in up to 76% yield, 96:4 dr, and 98:2 er.
- Kasten, Kevin,Slawin, Alexandra M. Z.,Smith, Andrew D.
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supporting information
p. 5182 - 5185
(2017/11/06)
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- Visible-Light-Promoted Vinylation of Tetrahydrofuran with Alkynes through Direct C-H Bond Functionalization
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(Chemical Equation Presented) Mild and direct C-H bond functionalizations and vinylations of tetrahydrofuran with alkynes have been accomplished through visible light photocatalysis, yielding a range of vinyl tetrahydrofurans under the synergistic actions of organic dye-type photocatalyst eosin Y, tert-butyl hydroperoxide (t-BuOOH), and a 45 W household lightbulb. A significant kinetic isotope effect (KIE) was recorded, which helps shed light on the mechanistic course.
- Li, Jing,Zhang, Jing,Tan, Haibo,Wang, David Zhigang
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supporting information
p. 2522 - 2525
(2015/05/27)
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- Formal anti-markovnikov hydroamination of terminal aryl alkynes with pinacolborane and hydroxylamines via Zr/Cu sequential catalysis
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We have explored a novel dry plasma process for the fabrication of electrodes on Nafion surfaces. Nanosized pillar structures were prepared through argon ion (Ar+) plasma treatment. The shear strengths of Au electrodes on plasma-treated Nafion surfaces were investigated. We found that the maximum shear strength (1.08 MPa) of Au-Nafion was observed under the optimal conditions (8 min, 100 W, 5 Pa, Ar+). Finally, we successfully prepared strongly bonded Au electrodes on Nafion through plasma surface treatment without using a wet plating process.
- Sakae, Ryosuke,Hirano, Koji,Satoh, Tetsuya,Miura, Masahiro
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supporting information
p. 1128 - 1130
(2013/10/22)
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- Regioselective preferential nucleophilic addition of N-heterocycles onto haloarylalkynes over N-arylation of aryl halides
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The study of preferential addition of heterocyclic amines onto halo-substituted arylalkynes over N-arylation under various catalytic conditions is described. The present work supports and confirms the mechanistic pathway of our recent work on the tandem synthesis of indolo- and pyrrolo-[2,1-a] isoquinolines via hydroamination followed by oxidative addition and not vice versa.
- Joshi, Megha,Tiwari, Rakesh,Verma, Akhilesh Kumar
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supporting information; body text
p. 1106 - 1109
(2012/04/10)
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- Regioselective solvent-dependent benzannulation of conjugated enynes
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The transformation of enynes under cobalt-catalysis leads to symmetrical benzannulation products in dichloromethane. In tetrahydrofuran the cobalt-catalysed reactions afforded the unprecedented unsymmetrical benzannulation products in moderate to good yields and good regioselectivities. In addition, cyclotrimerisation of the alkyne subunit can be realised when electron-deficient enynes are applied in the cobalt-catalysed transformations to generate 1,2,4-trivinylbenzene derivatives using tetrahydrofuran as solvent.
- Puenner, Florian,Hilt, Gerhard
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supporting information; experimental part
p. 3617 - 3619
(2012/05/20)
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- Base-mediated selective synthesis of diversely substituted N-heterocyclic enamines and enaminones by the hydroamination of alkynes
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Regio- and stereoselective alkynylation of various N-heterocycles 1a-l using potassium and cesium salts in DMSO is described. Terminal alkynes 2a-k and internal alkynes 4a-f provided the kinetically stable Z-enamines 3a-l and 5a-i in good to excellent yields using KOH at 120 °C. Addition of heterocyclic amines to 1,3- and 1,4-diethynylbenzene 6a-b provided the mixture of E/Z isomers with KOH; however, with Cs2CO3 selectively Z-isomers 7ab-db were obtained by the hydroamination at one triple bond. This developed methodology also provides an easy and novel access for the synthesis of enaminones 10a-c. The detailed work also supports the formation of cis-isomer by preferential addition of o-haloarylalkynes followed by intramolecular C2 arylation in the copper-catalyzed tandem synthesis of indolo and pyrrolo[2,1-a]isoquinolines.
- Joshi, Megha,Patel, Monika,Tiwari, Rakesh,Verma, Akhilesh K.
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experimental part
p. 5633 - 5645
(2012/08/07)
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- Pseudo five-component synthesis of 2,5-di(hetero)arylthiophenes via a one-pot Sonogashira-Glaser cyclization sequence
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Based upon a consecutive one-pot Sonogashira-Glaser coupling-cyclization sequence a variety of 2,5-di(hetero)arylthiophenes were synthesized in moderate to good yields. A single Pd/Cu-catalyst system, without further catalyst addition, and easily available, stable starting materials were used, resulting in a concise and highly efficient route for the synthesis of the title compounds. This novel pseudo five-component synthesis starting from iodo(hetero)arenes is particularly suitable as a direct access to well-defined thiophene oligomers, which are of peculiar interest in materials science.
- Urselmann, Dominik,Antovic, Dragutin,Mueller, Thomas J. J.
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supporting information; experimental part
p. 1499 - 1503
(2011/12/22)
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- Di-substituted pyridinyl aminohydantoins as potent and highly selective human β-secretase (BACE1) inhibitors
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The identification of highly selective small molecule di-substituted pyridinyl aminohydantoins as β-secretase inhibitors is reported. The more potent and selective analogs demonstrate low nanomolar potency for the BACE1 enzyme as measured in a FRET assay, and exhibit comparable activity in a cell-based (ELISA) assay. In addition, these pyridine-aminohydantoins are highly selectivity (>500×) against the other structurally related aspartyl proteases BACE2, cathepsin D, pepsin and renin. Our design strategy followed a traditional SAR approach and was supported by molecular modeling studies based on the previously reported aminohydantoin 3a. We have taken advantage of the amino acid difference between the BACE1 and BACE2 at the S2′ pocket (BACE1 Pro70 changed to BACE2 Lys86) to build ligands with >500-fold selectivity against BACE2. The addition of large substituents on the targeted ligand at the vicinity of this aberration has generated a steric conflict between the ligand and these two proteins, thus impacting the ligand's affinity and selectivity. These ligands have also shown an exceptional selectivity against cathepsin D (>5000-fold) as well as the other aspartyl proteases mentioned. One of the more potent compounds (S)-39 displayed an IC50 value for BACE1 of 10 nM, and exhibited cellular activity with an EC50 value of 130 nM in the ELISA assay.
- Malamas, Michael S.,Barnes, Keith,Johnson, Matthew,Hui, Yu,Zhou, Ping,Turner, Jim,Hu, Yun,Wagner, Erik,Fan, Kristi,Chopra, Rajiv,Olland, Andrea,Bard, Jonathan,Pangalos, Menelas,Reinhart, Peter,Robichaud, Albert J.
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experimental part
p. 630 - 639
(2010/04/26)
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- Improved and new syntheses of potential molecular electronics devices
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New syntheses of ethyl and nitro substituted oligo(phenylene ethynylene)s (OPEs) have been developed. To further explore whether the presence of nitro functionality in OPEs leads to switching and memory capabilities, new nitro substituted OPEs have been designed and synthesized. An isatogen-based system, a structure that is isomeric to the nitro OPE, has been synthesized. Additionally, pyridine-based and chromium-based compounds have been synthesized. We surmise that redox reactions of these candidates may impart switching capabilities and electrochemical studies are shown. U-shaped OPEs were synthesized to inhibit leakage of metals deposited during formation of top contacts on self-assembled monolayers (SAMs). The OPEs contain either thiol-based moieties or isonitrile groups to enable formation of SAMs on metal substrates.
- Price Jr., David W.,Dirk, Shawn M.,Maya, Francisco,Tour, James M.
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p. 2497 - 2518
(2007/10/03)
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- One-pot synthesis of symmetrical and unsymmetrical bisarylethynes by a modification of the sonogashira coupling reaction.
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A modification of the Sonogoshira coupling reaction employing an amidine base and a substoichiometric amount of water generates symmetrical and unsymmetrical bisarylethynylenes in one pot through in situ deprotection of trimethylsilylethynylene-added intermediates.
- Mio, Matthew J,Kopel, Lucas C,Braun, Julia B,Gadzikwa, Tendai L,Hull, Kami L,Brisbois, Ronald G,Markworth, Christopher J,Grieco, Paul A
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p. 3199 - 3202
(2007/10/03)
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- Synthesis and an X-ray structure of soluble phenylacetylene macrocycles with two opposing bipyridine donor sites
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The synthesis of the shape-persistent macrocycles 10a and 10b with two bipyridine units in opposing sides by Hagihara/Sonogashira cross-coupling chemistry of suitably functionalized building blocks is reported. X-ray analysis of single crystals of 10b sho
- Henze, Oliver,Lentz, Dieter,Schlueter, A. Dieter
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p. 2362 - 2367
(2007/10/03)
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- Ferromagnetic spin alignment in head-to-tail coupled oligo(1,4-phenyleneethynylene)s and oligo(1,4-phenylenevinylene)s bearing pendant p-phenylenediamine radical cations
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The intramolecular and long-range ferromagnetic coupling between p-phenylenediamine radical cations in head-to-tail coupled oligo(1,4-phenyleneethynylene)s and oligo(1,4-phenylenvinylene)s between neighbors and next-nearest neighbors is described. UV/vis/near-IR experiments show that the radical cations are localized in the pendant p-phenylenediamine units of the conjugated oligomers. The ESR spectra of these oligo(1,4-phenyleneethynylene) and oligo(1,4-phenylenvinylene) di(radical cation)s are consistent with those of a triplet state. A linear behavior is observed for the doubly integrated ESR intensity of the ΔM(s) = ±1 and ΔM(s) = ±2 signals with the inverse temperature (I ~ 1/T), consistent with Curie's law. This behavior indicates a triplet ground-state diradical with a large triplet-singlet energy gap or possibly a degeneracy of singlet and triplet states.
- Van Meurs, Pauline J.,Janssen, Rene A. J.
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p. 5712 - 5719
(2007/10/03)
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- (Alpha, omega) phenylethynyl siloxane monomers, oligomers, and polymers thereof
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Novel acetylene-terminated silicone monomers with (a) silane (Si-H) functionalities, (b) silanol (Si-OH) functionalities, or (c) (alpha,omega)phenylethynyl terminated siloxanes, and a novel synthetic route. The (alpha,omega)phenylethynyl-terminated siloxa
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- Novel 11 β-alkynylphenyl-10-nor-steroids
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Novel 11β-alkynylphenyl-19-nor-steroids of the formula STR1 wherein R1 is alkynyl of 2 to 8 carbon atoms optionally substituted with at least one member of the group consisting of --OH halogen, trialkylsilyl of 1 to 6 alkyl carbon atoms, alkoxy
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