- Synthesis, spectroscopic (FT-IR and UV-Vis), crystallographic and theoretical studies, and a molecular docking simulation of an imatinib-like template
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The aim of the present study was to report the crystal structure and spectroscopic, electronic, supramolecular and electrostatic properties of a new polymorph of 4-(pyridin-2-yl)pyrimidin-2-amine (C9H8N4). The compound was synthesized under microwave irradiation. The single-crystal X-ray structure analysis revealed an angle of 13.36 (8)° between the planes of the rings, as well as molecules linked by Nsp 2 - H?N hydrogen bonds forming dimers along the crystal. The material was analyzed by FT-IR vibrational spectroscopy, while a computational approach was used to elucidate the vibrational frequency couplings. The existence of Nsp 2 - H?N hydrogen bonds in the crystal was confirmed spectroscopically by the IR peaks from the N - H stretching vibration shifting to lower wavenumbers in the solid state relative to those in the gas phase. The supramolecular studies confirmed the formation of centrosymmetric R 2 2(8) rings, which correspond to the formation of dimers that stack parallel to the b direction. Other weak C - H?π interactions, essential for crystal growth, were found. The UV-Vis spectroscopic analysis showed a donor-acceptor process, where the amino group acts as a donor and the pyridine and pyrimidine rings act as acceptors. The reactive sites of the molecule were identified and their quantitative values were defined using the electrostatic potential model proposed in the multifunctional wave function analyzer multiwfn. The calculated interaction energies between pairs of molecules were used to visualize the electrostatic terms as the leading factors against the dispersion factors in the crystal-growth process. The docking results showed that the amino group of the pyrimidine moiety was simultaneously anchored by hydrogen-bonding interactions with the Asp427 and His407 protein residues. This compound could be key for the realization of a series of syntheses of molecules that could be used as possible inhibitors of chronic myelogenous leukemia.
- Moreno-Fuquen, Rodolfo,Arango-Daravi?a, Kevin,Garcia, Esteban,Tenorio, Juan-C.,Ellena, Javier
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- Selective Cadmium Fluorescence Probe Based on Bis-heterocyclic Molecule and its Imaging in Cells
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Fluorescence probes that selectively image cadmium are useful for detecting and tracking the amount of Cd2+ in cells and tissues. In this study, we designed and synthesized a novel Cd2+ fluorescence probe based on the pyridine-pyrimidine structure, 4-(methylsulfanyl)-6-(pyridin-2-yl)pyrimidin-2-amine (3), as a low-molecular-weight fluorescence probe for Cd2+. Compound 3 could successfully discriminate between Cd2+ and Zn2+ and exhibited a highly selective turn-on response toward Cd2+ over biologically related metal ions. The dissociation constant (Kd) and the limit of detection (LOD) of 5.4 × 10? 6?mol L? 1 and 4.4 × 10? 7?mol L? 1, respectively, were calculated using fluorescence titration experiments. Studies with closely related analogs showed that the bis-heterocyclic moiety of 3 acted as both a coordination site for Cd2+ and a fluorophore. Further, the methylsulfanyl group of compound 3 is essential for achieving selective and sensitive Cd2+ detection. Fluorescence microscopy studies using living cells revealed that the cell membrane permeability of compound 3 is sufficient to detect intracellular Cd2+. These results indicate that novel bis-heterocyclic molecule 3 has considerable potential as a fluorescence probe for Cd2+ in biological applications.
- Hagimori, Masayori,Karimine, Yasushi,Mizuyama, Naoko,Hara, Fumiko,Fujino, Takeshi,Saji, Hideo,Mukai, Takahiro
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p. 1161 - 1167
(2021/05/21)
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- Preparation method and application of N-(pyrimidine-2-yl) coumarin-7-amine derivative as protein kinase inhibitor
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The invention discloses a cyclin-dependent kinase inhibitor. The cyclin-dependent kinase inhibitor comprises an N-(pyrimidine-2-yl) coumarin-7-amine derivative shown as a general formula (I). In-vitropharmacodynamic tests prove that the compound has a high-selectivity inhibition effect on CDK9 kinase, and can be applied to reducing or inhibiting the activity of CDK9 kinase in cells. The inventionalso discloses a preparation method of the inhibitor and application of the inhibitor in drugs for CDK family kinase mediated diseases, especially hyperproliferative diseases, virus-induced infectious diseases and cardiovascular diseases.
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Paragraph 0223; 0227-0229; 0238; 0241-0243
(2020/12/14)
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- A Bipyridine-Palladium Derivative as General Pre-Catalyst for Cross-Coupling Reactions in Deep Eutectic Solvents
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A versatile and DES-compatible bipyridine palladium complex has been developed as a general pre-catalyst for different cross-coupling reactions (Hiyama, Suzuki-Miyaura, Heck-Mizoroki and Sonogashira) in deep eutectic solvents. Hydrogen bond capacity of the ligand allows to keep the excellent level of results previously obtained in classical organic solvents. Palladium pre-catalyst showed a high catalytic activity for many cross-coupling reactions, demonstrating a great versatility and applicability. Also, this methodology employs sustainable solvents as a reaction medium and highlights the potential of DES as alternative solvents in organometallic catalysis. The catalyst and DES were easily and successfully recycled. The formation of PdNPs in DES has been confirmed by TEM and XPS analysis and their role as catalyst by mercury test. The dynamic coordination of bipyridine-type ligand in the palladium complex formation has been studied via UV/Vis. (Figure presented.).
- Saavedra, Beatriz,González-Gallardo, Nerea,Meli, Alessandro,Ramón, Diego J.
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supporting information
p. 3868 - 3879
(2019/07/12)
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- SUBSTITUTED DIHYDROINDENE-4-CARBOXAMIDES AND ANALOGS THEREOF, AND METHODS USING SAME
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The present invention includes novel substituted bicyclic compounds, and compositions comprising the same, that can be used to treat or prevent hepatitis B virus (HBV) infections in a patient. In certain embodiments, the compounds and compositions of the invention are capsid inhibitors. (Formula I)
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Page/Page column 204; 206-207
(2018/10/19)
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- Mechanistic Studies on Ruthenium(II)-Catalyzed Base-Free Transfer Hydrogenation Triggered by Roll-Over Cyclometalation
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The synthesis of 2-substituted pyridine–pyrimidine ligands and their complexation with arene ruthenium(II) chloride moieties is reported. Depending on the electronic and steric influences of the ligand, the catalysts undergo CH activation by roll-over cyclometalation. This process opens up the route to the catalytic transfer hydrogenation of ketones with isopropanol as the hydrogen source under base-free and mild conditions. Barriers related to the roll-over cyclometalation process can be determined experimentally by collision-induced dissociation ESI mass spectrometry. They are supported by DFT calculations and allow the classification of the ligands according to their electronic and steric properties, which is also in accordance with critical bond parameters derived from X-ray structure data. DFT calculations furthermore reveal that the formation of a ruthenium(II) hydrido species is plausible through β-hydride elimination from isopropanol.
- Kerner, Christian,Lang, Johannes,Gaffga, Maximilian,Menges, Fabian S.,Sun, Yu,Niedner-Schatteburg, Gereon,Thiel, Werner R.
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p. 212 - 224
(2017/03/07)
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- Gold(i) complexes with heteroaryl phosphine ligands
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Gold(i) complexes ligated by phosphines with N-heterocycles in the periphery were prepared. First the synthesis of the ligands N- (diphenylphosphino)-4-(pyridin-2-yl)pyrimidin-2-amine (Hpypya) and N-(diphenylphosphino)-4-phenylpyrimidin-2-amine (Hphpya) a
- Sarcher, Christian,Farsadpour, Saeid,Taghizadeh Ghoochany, Leila,Sun, Yu,Thiel, Werner R.,Roesky, Peter W.
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p. 2397 - 2405
(2014/02/14)
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- C-H activation at a ruthenium(II) complex - The key step for a base-free catalytic transfer hydrogenation?
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Ruthenium(II) complexes [(η6-cymene)RuCl(apypm)]BPh 4 with bidentate 2-amino-4-(2-pyridinyl)pyrimidine (apypm) ligands catalyze the transfer hydrogenation of acetophenone. Their activities are strongly dependent on the substituent pattern of the pyrimidine ring. Complexes bearing a primary amino group in the 2-position of the pyrimidine ring do not perform the catalysis in terms of a "bifunctional mechanism", although they possess protic hydrogen atoms at the amino moiety in close proximity to the metal site. Systems containing tertiary dialkylated amino substituents at the apypm ligand are the first examples of air-stable and phosphane-free transfer-hydrogenation catalysts that show high activities even in the absence of a base. A new mechanism for the catalyst activation in the absence of an external base is proposed on the basis of ESI-MS investigations and ab initio calculations combined with isotope labelling: C-H bond cleavage at the pyrimidine ring is the crucial step for the generation of the catalytically active species. Phosphane-free air-stable ruthenium complexes catalyze the transfer hydrogenation of acetophenone in the absence of a base. Intramolecular C-H bond cleavage gives rise to a new catalyst activation mechanism, which was investigated through isotopic labelling, mass spectrometry and quantum chemical calculations.
- Taghizadeh Ghoochany, Leila,Kerner, Christian,Farsadpour, Saeid,Menges, Fabian,Sun, Yu,Niedner-Schatteburg, Gereon,Thiel, Werner R.
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supporting information
p. 4305 - 4317
(2013/09/12)
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- Study of the coordination and solution structures for the interaction systems between diperoxidovanadate complexes and 4-(pyridin-2-yl)pyrimidine-like ligands
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To understand the substitution effects of 4-(pyridin-2-yl)pyrimidine (pprd) on the coordination reaction equilibria, the interactions between a series of the pprd-like ligands and [OV(O2)2(H2O)] - or [OV(O2)2(HOD)]- or [OV(O 2)2(D2O)]- (bpV) have been explored by a combination of multinuclear (1H, 13C, and 51V) magnetic resonance, heteronuclear single quantum coherence (HSQC) and variable temperature NMR in a 0.15 mol L-1 NaCl D 2O solution that mimics physiological conditions. The direct NMR data are reported for the first time. Competitive coordination interactions result in a series of new hepta-coordinated peroxidovanadate species [OV(O 2)2LL′]- (LL′ = pprd-like chelating ligands). The equilibrium constants for the products between bpV and the pprd-like ligands show that the relative affinity of the ligands is pprd ≈ 2-NH2-pprd > 2-Me-pprd > 2-Et-pprd > 4-(6-methylpyridin-2- yl)pyrimidine (abbr. 6′-Me-pprd). When the ligand is pprd, a pair of isomers (Isomer A and B) are observed in aqueous solution, which are attributed to the different types of coordination modes between the metal and the ligands, while the crystal structure of NH4[OV(O2) 2(pprd)]·2H2O has the same coordination structure as Isomer A. For substituted pprd ligands, however, only one type of structure (Isomer A or B) is observed in solution. These results demonstrate that, when the aromatic ring has a substitution group, both the steric effect (from the alkyl) and hydrogen bonding (from the amine) can affect the coordination reaction equilibrium to prevent the appearance of either Isomer B in solution for the ligands 2-Me-pprd, 2-NH2-pprd, 2-Et-pprd, or Isomer A in solution for 6′-Me-pprd. The Royal Society of Chemistry 2012.
- Yu, Xian-Yong,Yi, Ping-Gui,Ji, Dan-Hong,Zeng, Bi-Rong,Li, Xiao-Fang,Xu, Xin
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supporting information; experimental part
p. 3684 - 3694
(2012/05/07)
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- A facile total synthesis of imatinib base and its analogues
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Imatinib and its analogues were successfully synthesized by an improved method in 19.5-46.2% total yield of six main steps. Pyrimidinyl amine was prepared by the reaction of enaminone and guanidine nitrate without the use of a toxic cyanamide. N-(2-Methyl-5-nitrophenyl)-4-(pyridin-3-yl) pyrimidin-2-amine as a key intermediate for the synthesis of imatinib was prepared by coppercatalyzed iV-arylation of heteroarylamme in 82% yield. The copper salts were used instead of the expensive palladium compounds in this C-N bond-forming reaction. The intermediate nitro compound was reduced by a N2H 4.H2O/FeCl3/C system using water as a solvent in good yield.
- Liu, Yi-Feng,Wang, Cui-Ling,Bai, Ya-Jun,Han, Ning,Jiao, Jun-Ping,Qi, Xiao-Li
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p. 490 - 495
(2013/01/03)
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- The reaction of enaminones with carboxamidines: A convenient route for the synthesis of polyaza heterocycles
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A simple and efficient synthetic method to polyaza heterocyclic structures containing 1,3-pyrimidine units has been developed. It is based on the reaction of the enaminones such as 5, 7 and 9 with the appropriate carboxamidines under basic conditions. By this procedure several new polyaza heterocycles have been prepared in good yields.
- Bejan,Ait Haddou,Daran,Balavoine
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p. 1012 - 1018
(2007/10/03)
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