612-28-2Relevant articles and documents
Deciphering the Influence of Meridional versus Facial Isomers in Spin Crossover Complexes
Lathion, Timothée,Guénée, Laure,Besnard, Céline,Bousseksou, Azzedine,Piguet, Claude
, p. 16873 - 16888 (2018)
Chelate coordination of non-symmetrical didentate pyrazine-benzimidazole (L1) or pyridine-benzimidazole (L2) N-donor ligands around divalent iron in acetonitrile produces stable homoleptic triple-helical spin crossover [Fe(Lk)3]2+ complexes existing as mixtures of meridional (C1-symmetry) and facial (C3-symmetry) isomers in slow exchange on the NMR timescale. The speciation deviates from the expected statistical ratio mer/fac=3:1, a trend assigned to the thermodynamic trans-influence, combined with solvation effects. Consequently, the observed spin state FeIIlow-spin?FeIIhigh-spin equilibria occurring in [Fe(Lk)3]2+ refer to mixtures of complexes in solution, an issue usually not considered in this field, but which limits rational structure-properties correlations. Taking advantage of the selective and quantitative formation of isostructural facial isomers in non-constrained related spin crossover d-f helicates (HHH)-[LnFe(Lk)3]5+ (Ln is a trivalent lanthanide, Lk=L5, L6), we propose a novel strategy for assigning pertinent thermodynamic driving forces to each spin crossover triple-helical isomer. The different enthalpic contributions to the spin state equilibrium found in mer-[Fe(Lk)3]2+ and fac-[Fe(Lk)3]2+ reflect the Fe?N bond strengths dictated by the trans-influence, whereas a concomitant solvent-based entropic contribution reinforces the latter effect and results in systematic shifts of the spin crossover transitions toward higher temperature in the facial isomers.
Tuning spin-crossover transition temperatures in non-symmetrical homoleptic meridional/facial [Fe(didentate)3]2+complexes: what for and who cares about it?
Deorukhkar, Neel,Besnard, Céline,Guénée, Laure,Piguet, Claude
, p. 1206 - 1223 (2021/02/09)
The [FeN6] chromophores found in [Fe(didentate)3]2+complexes, where didentate is a non-symmetrical 2-(6-membered-heterocyclic ring)-benzimidazole ligand (Lk), exist as mixtures of two geometricalmer(C1-symmetry) andfac(C3-symmetry) isomers. Specific alkyl-substituted six-membered heterocyclic rings connected to the benzimidazole unit (pyridines in ligandsL1-L3, pyrazines inL4-L5and pyrimidines inL6-L7) control the ligand field strength and the electron delocalization so that [FeII(Lk)3]2+display tunable thermally-induced spin transitions in solution. Thermodynamic, spectroscopic (UV-Vis, NMR) and magnetic studies in solution demonstrate that [Fe(L6)3]2+(L6= 1-methyl-2-(pyrimidin-2-yl)-1H-benzo[d]imidazole) exhibits a close to room temperature spin transition (T1/2= 273(3) K) combined with a high stability formation constant n acetonitrile), which makes this complex suitable for the potential modulation of lanthanide-based luminescence in polymetallic helicates. A novel method is proposed for assigning specific thermodynamic spin crossover parameters tofac-[Fe(L6)3]2+andmer-[Fe(L6)3]2+isomers in solution. The observed difference relies mainly on the entropic content ΔSmerSCO? ΔSfacSCO= 11(1) J mol?1K?1, which favors the spin transition for the meridional isomer. Intermolecular interactions occurring in the crystalline state largely overcome minor thermodynamic trends operating in diluted solutions and a single configurational isomer is usually observed in the solid state. Among the thirteen solved crystal structures1-13containing the [M(Lk)3]2+cations (M = Fe, Ni, Zn,Lk=L6-L7), pure meridional isomers are observed six times, pure facial isomers also six times and a mixture (44%merand 56%fac) is detected only once. Solid-state magnetic data recorded for the FeIIcomplexes show the operation of slightly cooperative spin transitions in7(fac-[Fe(L6)3]2+) and12(mer-[Fe(L7)3]2+). For the meridional isomer in6, a two-step spin state transition curve, associated with two phase transitions, is detected.
N-substituted benzimidazole acrylonitriles as in vitro tubulin polymerization inhibitors: Synthesis, biological activity and computational analysis
Perin,Hok,Be?,Persoons,Vanstreels,Daelemans,Vianello,Hranjec
, (2020/12/02)
We present the design, synthesis and biological activity of novel N-substituted benzimidazole based acrylonitriles as potential tubulin polymerization inhibitors. Their synthesis was achieved using classical linear organic and microwave assisted techniques, starting from aromatic aldehydes and N-substituted-2-cyanomethylbenzimidazoles. All newly prepared compounds were tested for their antiproliferative activity in vitro on eight human cancer cell lines and one reference non-cancerous assay. N,N-dimethylamino substituted acrylonitriles 30 and 41, bearing N-isobutyl and cyano substituents placed on the benzimidazole nuclei, showed strong and selective antiproliferative activity in the submicromolar range of inhibitory concentrations (IC50 0.2–0.6 μM), while being significantly less toxic than reference systems docetaxel and staurosporine, thus promoting them as lead compounds. Mechanism of action studies demonstrated that two most active compounds inhibited tubulin polymerization. Computational analysis confirmed the suitability of the employed benzimidazole-acrylonitrile skeleton for the binding within the colchicine binding site in tubulin, thus rationalizing the observed antitumor activities, and demonstrated that E-isomers are active substances. It also provided structural determinants affecting both the binding position and the matching affinities, identifying the attached NMe2 group as the most dominant in promoting the binding, which allows ligands to optimize favourable cation???π and hydrogen bonding interactions with Lys352.
Discovery of a Highly Selective Sigma-2 Receptor Ligand, 1-(4-(6,7-Dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)butyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one (CM398), with Drug-Like Properties and Antinociceptive Effects In Vivo
Avery, Bonnie A.,Chin, Frederick T.,Intagliata, Sebastiano,King, Tamara I.,Matsumoto, Rae R.,McCurdy, Christopher R.,McLaughlin, Jay P.,Mesangeau, Christophe,Seminerio, Michael,Sharma, Abhisheak,Wilson, Lisa L.
, (2020/07/25)
The sigma-2 receptor has been cloned and identified as Tmem97, which is a transmembrane protein involved in intracellular Ca2+ regulation and cholesterol homeostasis. Since its discovery, the sigma-2 receptor has been an extremely controversial target, and many efforts have been made to elucidate the functional role of this receptor during physiological and pathological conditions. Recently, this receptor has been proposed as a potential target to treat neuropathic pain due to the ability of sigma-2 receptor agonists to relieve mechanical hyperalgesia in mice model of chronic pain. In the present work, we developed a highly selective sigma-2 receptor ligand (sigma-1/sigma-2 selectivity ratio > 1000), 1-(4-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)butyl)-3-methyl-1H- benzo[d]imidazol-2(3H)-one (CM398), with an encouraging in vitro and in vivo pharmacological profile in rodents. In particular, radioligand binding studies demonstrated that CM398 had preferential affinity for sigma-2 receptor compared with sigma-1 receptor and at least four other neurotransmitter receptors sites, including the norepinephrine transporter. Following oral administration, CM398 showed rapid absorption and peak plasma concentration (Cmax) occurred within 10?min of dosing. Moreover, the compound showed adequate, absolute oral bioavailability of 29.0%. Finally, CM398 showed promising anti-inflammatory analgesic effects in the formalin model of inflammatory pain in mice. The results collected in this study provide more evidence that selective sigma-2 receptor ligands can be useful tools in the development of novel pain therapeutics and altogether, these data suggest that CM398 is a suitable lead candidate for further evaluation.
HMOX1 inducers
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Page/Page column 159, (2020/09/18)
The present invention is related to compounds of structure (I) as heme oxygenase 1 (HMOX 1) inducers. The present invention is also related a method of controlling the activity or the amount, or both the activity and the amount, of heme-oxygenase 1 in a mammalian subject. The definitions of the variables are provided herein.
Benzimidazole derivatives as potent and isoform selective tumor-associated carbonic anhydrase IX/XII inhibitors
?al??kan, Burcu,Banoglu, Erden,Gür Maz, Tu??e,Nocentini, Alessio,Supuran, Claudiu T.,Uslu, Azize Gizem
supporting information, (2020/01/08)
We describe the synthesis of a series of 2-arylbenzimidazole derivatives bearing sulfonamide functionality (4a–d, 7a–c and 10) as well as hydroxamic acid (15a–b), carboxylic acid (16a–b), carboxamide (17a–b) and boronic acid (22a–b and 26) functionalities, which act as human carbonic anhydrase (hCA, EC 4.2.1.1) inhibitors. The newly synthesized benzimidazole derivatives were evaluated against 4 physiologically relevant CA isoforms (hCA I, II, IX, and XII), and especially the sulfonamide-containing benzimidazoles demonstrated intriguing inhibitory activity against tumor associated CA IX and XII with KI values in the range of 5.2–29.3 nM and 9.9–41.7 nM, respectively. Notably, compound 4c was the most potent and selective CA IX (KI = 6.6 nM) and XII (KI = 9.9 nM) inhibitor with a significant selectivity ratio over cytosolic CA I and II isoforms in the range of 3.4–25.2. In addition, compounds having hydroxamic acid (15a-b) or carboxylic acid (16a-b) functionalities resulted in greater selectivity ratios for CA IX/XII over CAI/II in the range of 4.1–121.5 although with KI values in lower micromolar potency (KIs = 0.36–0.85 μM for CA IX/XII).
Synthesis method of N-methyl-1,2-benzenediamine dihydrochloride
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Paragraph 0031-0033; 0036; 0037; 0040; 0041, (2019/10/05)
The invention discloses a synthesis method of N-methyl-1,2-benzenediamine dihydrochloride. The synthesis method is characterized by comprising the following steps that 1, o-chloronitrobenzene and a monomethylamine aqueous solution are subjected to a sealing reaction, after the reaction is completed, cooling, standing and layering are conducted, and a lower-layer oil phase is collected to obtain N-methyl-2-nitroaniline; 2, a catalyst is added to a mixed solution of ethyl alcohol and the N-methyl-2-nitroaniline obtained in step 1, after mixing and heating, hydrazine hydrate is slowly dropwise added to the mixed solution, and after drop addition is completed, a heat preservation reaction is conducted; after the reaction is completed, suction filtration is conducted, and a suction filtration mother solution is reserved to obtain N-methyl-o-phenylenediamine; 3, liquid caustic soda, water and EDTA are added to the N-methyl-o-phenylenediamine obtained in step 2 for mixing, after cooling is conducted, dichloromethane is added, stirring, extraction, standing and layering are conducted, a lower-layer oil phase is collected, and through separation and purification, the target product N-methyl-1,2-benzenediamine dihydrochloride is obtained. The N-methyl-1,2-benzenediamine dihydrochloride product prepared through the method has high purity and few impurities and can be widely applied to the field of intermediate synthesis of a medicine tishamitan for reducing the blood pressure.
Iridium complex and organic light-emitting device (OLED)
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Paragraph 0070-0073, (2018/12/02)
The invention discloses an iridium complex and an organic light-emitting device (OLED), and relates to the technical field of organic photoelectric materials. On the one hand, a guanidine group with acarbene-like structure is introduced into a metal complex molecule as an ancillary ligand, and a four-membered ring coordination structure is constructed, so that a series of green phosphorescence complex material systems with brand-new molecular structures and photoelectric properties are obtained. The iridium complex has more stable central positive trivalent ruthenium atoms, thus having betterchemical stability and thermal stability; furthermore, the iridium complex can reduce unnecessary vibration energy loss, so that the non-radiative transition of the molecules is reduced, and the luminous efficiency of the complex is accordingly increased. On the other hand, an alkyl structure is introduced into the structure, so that the solubility of the ruthenium complex is improved. A device is prepared by carrying out diffraction on the iridium complex, especially using the iridium complex as a doping material; the device shows the advantages of being low in driving voltage, high in luminous efficiency and better in color purity, and is superior to the existing common OLED devices.
A N - methyl O-phenylenediamine hydrochloride synthetic method (by machine translation)
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Paragraph 0004; 0015-0020, (2018/12/02)
The invention discloses a N - methyl O-phenylenediamine hydrochloride synthetic method, steps (1) O-nitro-chlorobenzene and under the action of a methyl amine, to obtain the product N - methyl O-nitroaniline, step (2) step (1) the obtained product N - methyl O-nitroaniline crude product is dissolved in the methanol in the solvent, to the palladium-carbon as the catalyst, hydrogenation reduction to obtain N - methyl O-phenylenediamine, filtering out catalyst, to boil off the methanol solvent, adding hydrochloric acid generating N - methyl O-phenylenediamine hydrochloride. Synthesis method of the invention for the purpose of the O-nitro-chlorobenzene route to synthesize the product, low cost has extremely strong competitiveness. The reduction in hydrogen as the reducing agent, the reduction efficiency is high, no iron powder, sodium sulfide, substances such as hydrazine hydrate reduction generated when the pollution problem, nor reduction when the hydrazine hydrate, relates to toxicity problems. And the hydrogenation reduction of the product after the treatment is simple, the product quality is high, to post-drug a reliable guarantee for the quality of the product. In addition the use of the solvent is methanol, can be combined and then recovering the recycled. (by machine translation)
Tetraphenylethylene-based blue light material containing benzimidazole unit as well as preparation method and application
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Paragraph 0027; 0028; 0029; 0081; 0082; 0083, (2017/10/10)
The invention discloses a tetraphenylethylene-based blue light material containing a benzimidazole unit. The tetraphenylethylene-based blue light material is shown as a structural formula I or II, wherein R1 is H, tert-butyl, n-butyl or hydroxyl, and R2 is alkyl. A 2-nitro-N-tert-butylphenyl amine or 2-nitro-N-n-butylphenyl amine precursor and a 4-formyl tetraphenylethylene precursor is firstly prepared, and then cyclization reaction is carried out to prepare a compound shown as the formula I or II. A preparation method of the compound is easy to operate, the reaction is moderate and the yield is high; the compound has relatively high decomposition temperature and glass-transition temperature, and shows blue fluorescence; the compound has a relatively good single-color property, so that an OLED (Organic Light Emitting Diode) device prepared by taking the compound as a luminescent material emits blue light; the starting voltage is 3.3V and the maximum brightness efficiency is 1.48cd/A. (The formula I and the formula II are shown in the description).
