81294-10-2Relevant articles and documents
Hybrid conjugated organic oligomers consisting of oligodiacetylene and thiophene units: Synthesis and optical properties
Pilzak, Gregor S.,Van Gruijthuijsen, Kitty,Van Doom, Reindert H.,Van Lagen, Barend,Sudhoelter, Ernst J. R.,Zuilhof, Han
, p. 9085 - 9096 (2009)
Novel and highly soluble hybrid conjugated organic oligomers consisting of oligodiacetylene and thiophene units have been synthesized in high purity through iterative and divergent approaches based on a sequence of Sonogashira reactions. The series of thiophene-containing oligodiacetylenes (ThODAs) and homocoupled ThODAs (HThODAs) show-both in solution and in the solid state-a strong optical absorption, which is progressively red shifted with increasing chain length. The linear correlation of the absorption maximum (λAmax) with the inverse of conjugation length (CL = number of double and triple bonds) shows that the effective conjugation length of this system is extended up to at least CL = 20. Furthermore, absorption measurements of dropcast thin films display not only a bathochromic shift of the absorption maxima but also a higher wavelength absorption, which is attributed to increased π-π interactions. The wavelength of the maximum fluorescence emission (λEmax) also increases with CL, and emission is maximal for oligomers with CL = 7-12 (fluorescence quantum yield φF = ～0.2). Both longer and shorter oligomers display marginal emission. The calculated Stokes shifts of these planar materials are relatively large (0.4 eV) for all oligomers, and likely due to excitation to the S2 state, thus suggesting that the presence of enyne moieties dominates the ordering of the lowest excited states. The fluorescence lifetimes (τF) are short (τF'max =Le; 1ns) and closely follow the tendency obtained for the fluorescence quantum yield. The anisotropy lifetimes show a near-linear increase with CL, in line with highly rigid oligomers.
Dimerization of Substituted Arylacetylenes - Quantum Chemical Calculations and Kinetic Studies
Fabig, Sven,Janiszewski, Alexandra,Flo?, Martin,Kreuzahler, Mathis,Haberhauer, Gebhard
, p. 7878 - 7885 (2018)
The dimerization of substituted arylacetylenes is a very interesting tool to generate 1,3-butadiene 1,4-diradicals. Recently, it was shown that electron-withdrawing groups attached to the triple bond reduce the activation barrier and increase the stability of the diradical intermediates. Here, we investigate the influence of the π donor character of substituents, which are bound to the aryl system, on the dimerization reaction of arylacetylenes. Both quantum chemical calculations and kinetic studies reveal that the higher the π donor character of substituents, the lower the activation barrier. The highest observed difference between the model systems amounts to 4.0 kcal/mol, which represents an acceleration by a factor of 700. However, according to the calculations the π donor character of the substituents increases the diradical character of the intermediates.
Design, synthesis, and biological evaluation of novel 2′-methyl-2′-fluoro-6-methyl-7-alkynyl-7-deazapurine nucleoside analogs as anti-Zika virus agents
Yao, Guoqiang,Yu, Jianchen,Lin, Cai,Zhu, Yujia,Duan, Anna,Li, Mengfeng,Yuan, Jie,Zhang, Jiancun
supporting information, (2022/03/23)
Zika virus (ZIKV) is a mosquito-borne flavivirus and outbreaks of ZIKV have been reported in Africa, Americas and other parts of the world lately. The ZIKV epidemic has received extensive attention due to its ability to cause serious medical consequences and complications such as microcephaly and Guillain-Barre syndrome in recent years. Up to now, there are no specific treatments or vaccines available for ZIKV infection, which highlights the urgent need for developing new therapies. In this work, we designed and synthesized a series of novel 6-methyl-7-acetylenenyl-7-deazapurine nucleoside analogs as potential inhibitors of ZIKV replication. The biological activities against ZIKV replication were evaluated and the structure-activity relationship (SAR) was also studied. Among the compounds evaluated, nucleoside analog 38 (EC50 = 2.8 ± 0.8 μM, EC90 = 6.8 ± 2.3 μM) showed the most potent anti-ZIKV activity with low cytotoxicity (CC50 = 54.1 ± 6.9 μM) in an A549 based cellular model. The inhibitory activity of 38 was about 5 times more potent than the positive control NITD008. Notably, 38 showed similar inhibition potency against different ZIKV strains (ZG-01 and MR766) in a variety of host cell types including SNB19, A549, Huh7, Vero. In addition, 38 (Kd = 1.87 μM) has a stronger affinity to ZIKV RNA-dependent RNA polymerase (RdRp) protein than NITD008 (Kd = 3.43 μM) in the non-phosphorylation assay. These results indicated that compound 38 may serve as a promising candidate in future anti-ZIKV drug discovery.
Pyrazole-Based Lactate Dehydrogenase Inhibitors with Optimized Cell Activity and Pharmacokinetic Properties
Rai, Ganesha,Urban, Daniel J.,Mott, Bryan T.,Hu, Xin,Yang, Shyh-Ming,Benavides, Gloria A.,Johnson, Michelle S.,Squadrito, Giuseppe L.,Brimacombe, Kyle R.,Lee, Tobie D.,Cheff, Dorian M.,Zhu, Hu,Henderson, Mark J.,Pohida, Katherine,Sulikowski, Gary A.,Dranow, David M.,Kabir, Md,Shah, Pranav,Padilha, Elias,Tao, Dingyin,Fang, Yuhong,Christov, Plamen P.,Kim, Kwangho,Jana, Somnath,Muttil, Pavan,Anderson, Tamara,Kunda, Nitesh K.,Hathaway, Helen J.,Kusewitt, Donna F.,Oshima, Nobu,Cherukuri, Murali,Davies, Douglas R.,Norenberg, Jeffrey P.,Sklar, Larry A.,Moore, William J.,Dang, Chi V.,Stott, Gordon M.,Neckers, Leonard,Flint, Andrew J.,Darley-Usmar, Victor M.,Simeonov, Anton,Waterson, Alex G.,Jadhav, Ajit,Hall, Matthew D.,Maloney, David J.
supporting information, p. 10984 - 11011 (2020/11/09)
Lactate dehydrogenase (LDH) catalyzes the conversion of pyruvate to lactate, with concomitant oxidation of reduced nicotinamide adenine dinucleotide as the final step in the glycolytic pathway. Glycolysis plays an important role in the metabolic plasticity of cancer cells and has long been recognized as a potential therapeutic target. Thus, potent, selective inhibitors of LDH represent an attractive therapeutic approach. However, to date, pharmacological agents have failed to achieve significant target engagement in vivo, possibly because the protein is present in cells at very high concentrations. We report herein a lead optimization campaign focused on a pyrazole-based series of compounds, using structure-based design concepts, coupled with optimization of cellular potency, in vitro drug-target residence times, and in vivo PK properties, to identify first-in-class inhibitors that demonstrate LDH inhibition in vivo. The lead compounds, named NCATS-SM1440 (43) and NCATS-SM1441 (52), possess desirable attributes for further studying the effect of in vivo LDH inhibition.
Cyclization of Diaryl(hetaryl)alkynes under Selenobromination Conditions: Regioselectivity and Mechanistic Studies
Paegle, Edgars,Belyakov, Sergey,Petrova, Marina,Liepinsh, Edvards,Arsenyan, Pavel
supporting information, p. 4389 - 4399 (2015/07/27)
The cyclization of substituted diaryl(hetaryl)alkynes with in-situ-prepared SeBr4 has been achieved. The use of an alkene additive as a bromine scavenger gives simple access to functionalized benzo[b]selenophene and selenophenothiophene derivatives from commercially available or easily accessible starting materials. The reactions can be performed in air without the use of moisture-sensitive reagents, dry solvents, or an inert atmosphere. Mechanistic studies confirmed a regioselective anti 1,2-addition in the selenobromination step, and a subsequent electrophilic substitution in the aromatic ring to complete the cyclization. The cyclization of substituted diaryl(hetaryl)alkynes with in-situ-prepared SeBr4 has been achieved. The use of an alkene additive as a bromine scavenger gives simple access to functionalized benzo[b]selenophene and selenophenothiophene derivatives from commercially available or easily accessible starting materials.
Five-Membered Heterocycles as Linking Units in Strongly Coupled Homobimetallic Group 8 Metal Half-Sandwich Complexes
Pfaff, Ulrike,Hildebrandt, Alexander,Korb, Marcus,Schaarschmidt, Dieter,Rosenkranz, Marco,Popov, Alexey,Lang, Heinrich
, p. 2826 - 2840 (2015/06/30)
The synthesis and characterization of a series of alkynyl half-sandwich complexes of type 2,5-((η5-C5H5)(dppe)MC≡C)2-cC4H2E (E = O (11), S (12); M = Fe (a), Ru (b); dppe = 1,2-bis(diphenylphosphino)ethane) are reported. The molecular structures of 11a and 12a,b in the solid state have been determined by single-crystal X-ray diffraction. The influence of different metals and the variation of the heterocyclic bridge on the electronic interactions between the terminal redox-active units in 11a,b and 12a,b was studied using electrochemical (cyclic and square wave voltammetry) and spectroelectrochemical (in situ UV-vis/NIR, ESR, and IR spectroscopy) methods and DFT calculations. Electrochemical studies demonstrated that mixed-valent species 11a,b+ and 12a,b+ exhibit high thermodynamic stabilities with respect to disproportionation (KC values from 6.87 × 104 to 9.33 x 105). In situ spectroelectrochemical ESR and IR measurements display delocalization of the single electron between the metal centers M/M+, revealing that within this setup five-membered heterocycles are well suited to promote intramolecular metal-metal interactions. Furthermore, the UV-vis/NIR spectra of mixed-valent 11a,b+ and 12a,b+ show intense, narrow, and nonsolvatochromic π(dπ) → π(dπ) absorptions in the NIR region with a high-energy shoulder. Both experimental and computational results suggest that at least two thermally accessible rotation conformers of the organometallic termini of 11a,b and 12a,b contribute to the electronic spectra of these compounds. One of the conformers can clearly be characterized as a delocalized class III system, while the other shows a more localized behavior. (Figure Presented).
Cross-coupling of nonactivated alkyl halides with alkynyl grignard reagents: A nickel pincer complex as the catalyst
Vechorkin, Oleg,Godinat, Aurélien,Scopelliti, Rosario,Hu, Xile
supporting information; experimental part, p. 11777 - 11781 (2012/01/19)
In a pinch: The nickel pincer complex 1 catalyzes the cross-coupling of the title compounds with remarkable substrate scope and functional group tolerance. A nickel/alkynyl species was isolated and shown to be catalytically competent. THF=tetrahydrofuran, O-TMEDA=bis[2-(N,N-dimethylaminoethyl)] ether. Copyright
Direct synthesis of heteroarylethynes via palladiumcatalyzed coupling of heteroaryl halides with ethynylzinc halides. Its application to an efficient synthesis of a thiophenelactone from chamaemelum nobile
Negishi, Ei-Ichi,Xu, Caiding,Tan, Ze,Kotora, Martin
, p. 209 - 214 (2007/10/03)
A variety of terminal alkynes containing a heteroaryl group can be directly and selectively synthesized by the Pd-catalyzed coupling of heteroaryl iodides or bromides with ethynylzinc halides. Various compounds of this class containing furan, thiophene, and pyridine have been prepared, and the procedure has been applied to an efficient and selective synthesis of a thiophenelactone from Chamaemelum nobile L.
PALLADIUM-MEDIATED REACTION BETWEEN ARYL IODIDES AND STEREODEFINED 2-ARYLETHENYLDIMETHYLPHENYLSILANES OR 2-ARYLETHYNYLDIMETHYLPHENYLSILANES, IN THE PRESENCE OF A FLUORIDE ION SOURCE
Rossi, Renzo,Carpita, Adriano,Messeri, Tommaso
, p. 65 - 72 (2007/10/02)
Stereodefined 2-arylethenyldimethylphenylsilanes, 1, do react with aryl iodides, 6, containing an electron-donating substituent as well as with 2-thienyl iodide, 7, in the presence of a catalytic amount of a palladium complex and a molar excess of a 1 M T
