- Synthesis of new quinoxaline derivatives
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New quinoxaline derivatives were prepared by the reaction of 2-hydroxyquinoxaline 1 and alkyl or alkylaminoalkyl halides in dimethylformamide using potassium carbonate as a base. The hydroxyl group was readily converted into a thiol function by treatment with phosphorus pentasulfide and/or Lawesson's reagent in pyridine, and the subsequent alkylation of the thiol group was carried out under phase-transfer catalyst conditions. Chlorination of 1 was carried out with phosphorus oxychloride. Branching of alkylamino side chains to the 2-OH, 2-SH, and 2-Cl quinoxalines resulted in the synthesis of several compounds. Synthesis and alkylation of 2-hydroxy 7-nitroquinoxaline are also reported.
- Makhloufi,Baitiche,Merbah,Benachour
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- An improved method for chlorination of nitrogen-containing π-deficient heteroaromatics using triphenylphosphine and trichloroisocyanuric acid
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Phosphorus compound prepared by reaction of triphenylphosphine with trichloroisocyanuric acid was found to be applied to chlorination of nitrogen-containing π-deficient heteroaromatics. As self-decomposition of the chlorinating reagent hardly proceeds, the reagent is more useful than phosphorus compound prepared by triphenylphosphine and N-chlorosuccinimide.
- Sugimoto, Osamu,Tanji, Ken-ichi
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- Synthesis and antimicrobial activity of some 2(1H)-quinoxalinone-6-sulfonyl derivatives
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The synthesis of some quinoxalinesulfonyl derivatives is described. Two of the synthesized derivatives, 2-oxo-1,2-dihydroquinoxaline-6-sulfonyl azide (3a) and 2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonyl azide (3b), were screened in vitro for their growth inhibitory activity against nine strains of Gram-positive and seven strains of Gram-negative bacteria, along with two fungal isolates. The two compounds showed broad spectrum (in vitro) activity against the bacterial strains. Copyright Taylor & Francis Inc.
- Obafemi, Craig A.,Akinpelu
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Read Online
- Novel gas-phase cyclisation reactions of 2-(1-pyrazolyl)phenylnitrenes
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Flash vacuum pyrolysis of the azide 3 gives a mixture of pyrazolobenzotriazole 2, quinoxaline 5 and pyrazolobenzimidazole 4 derived from the corresponding nitrene.
- Clark, Bernard A. J.,McNab, Hamish,Sommerville, Craig C.
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- Synthesis, antiviral and antibacterial activities and action mechanism of penta-1,4-dien-3-one oxime ether derivatives containing a quinoxaline moiety
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A series of penta-1,4-dien-3-one oxime ether derivatives containing a quinoxaline moiety were synthesized and their antibacterial and antiviral activities were evaluated. Bioassay activity indicated that some of the compounds displayed significant antibacterial and antiviral activities. In particular, some title compounds were found to show remarkable antiviral activities against tobacco mosaic virus (TMV). Compound 6i showed remarkable curative, protective and inactivation activity against TMV, with a 50% effective concentration (EC50) of 287.1, 157.6 and 133.0 μg mL-1, respectively. These results were better than or comparable to those of ningnanmycin (356.3, 233.7 and 121.6 μg mL-1, respectively). Microscale thermophoresis (MST) also showed that the binding of compound 6i to TMV coat protein (TMV-CP) gave a Kd value of 0.115 ± 0.092 μmol L-1, which was better than that of ningnanmycin (0.523 ± 0.254 μmol L-1). Meanwhile, the EC50 values of compound 6k against Xanthomonas axonopodis pv. Citri (Xac) and Xanthomonas oryzae pv. oryzae (Xoo) were 16.8 and 33.4 μg mL-1 respectively, and that of compound 6i against Ralstonia solanacearum (Rs) was 33.9 μg mL-1. These results were better than those of bismerthiazol (44.3, 42.5 and 62.4 μg mL-1, respectively). The mechanism of antibacterial action of compound 6k against Xac was analysed through scanning electron microscopy (SEM). This study indicated that the title compounds are valuable in the search for novel agrochemicals.
- Xia, Rongjiao,Guo, Tao,Chen, Mei,Su, Shijun,He, Jun,Tang, Xu,Jiang, Shichun,Xue, Wei
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- A Computer-Driven Scaffold-Hopping Approach Generating New PTP1B Inhibitors from the Pyrrolo[1,2-a]quinoxaline Core
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Protein tyrosine phosphatase 1B (PTP1B) is a very promising target for the treatment of metabolic disorders such as type II diabetes mellitus. Although it was validated as a promising target for this disease more than 30 years ago, as yet there is no drug in advanced clinical trials, and its biochemical mechanism and functions are still being studied. In the present study, based on our experience generating PTP1B inhibitors, we have developed and implemented a scaffold-hopping approach to vary the pyrrole ring of the pyrrolo[1,2-a]quinoxaline core, supported by extensive computational techniques aimed to explain the molecular interaction with PTP1B. Using a combination of docking, molecular dynamics and end-point free-energy calculations, we have rationally designed a hypothesis for new PTP1B inhibitors, supporting their recognition mechanism at a molecular level. After the design phase, we were able to easily synthesize proposed candidates and their evaluation against PTP1B was found to be in good concordance with our predictions. Moreover, the best candidates exhibited glucose uptake increments in cellulo model, thus confirming their utility for PTP1B inhibition and validating this approach for inhibitors design and molecules thus obtained.
- García-Marín, Javier,Griera, Mercedes,Alajarín, Ramón,Rodríguez-Puyol, Manuel,Rodríguez-Puyol, Diego,Vaquero, Juan J.
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p. 2895 - 2906
(2021/07/21)
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- Design and Synthesis of Some New N-Phenyl-[1,2,4]triazolo[4,3-a]quinoxaline-1-sulfonamide Derivatives and Their Anti-Cancer Activity
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Abstract: Synthesis of some new derivatives of N-phenyl-[1,2,4]triazolo [4,3-a]quinoxaline-1-sulfonamide and their in vitro anticancer activity on four human cancer lines like MCF-7 (human breast cancer cell line), HeLa (human cervical cancer cell line), A549 (human lung cancer cell line), and IMR32 (human neuroblastoma cell line) have been studied. Among the products, N-(3,5-dichloronitrophenyl)-[1,2,4] triazolo[4,3-a]quinoxaline-1-sulfonamide, is characterized by the activity higher than the standard Etoposide against the tested cancer cell lines.
- Badithapuram, Vinitha,Bandari, Srinivas,Dasari, Gouthami,Nukala, Satheesh Kumar,Pandiri, Madhuri
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p. 2280 - 2285
(2021/12/23)
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- One-pot multicomponent synthesis of novel 2-(piperazin-1-yl) quinoxaline and benzimidazole derivatives, using a novel sulfamic acid functionalized Fe3O4 MNPs as highly effective nanocatalyst
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The immobilization of sulfonic acid on the surface of Fe3O4 magnetic nanoparticles (MNPs) as a novel acid nanocatalyst has been successfully reported. The morphological features, thermal stability, magnetic properties, and other physicochemical properties of the prepared superparamagnetic core–shell (Fe3O4@PFBA–Metformin@SO3H) were thoroughly characterized using Fourier transform infrared (FTIR), X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDS), field-emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), thermogravimetric analysis–differential thermal analysis (TGA-DTA), atomic force microscopy (AFM), dynamic light scattering (DLS), Brunauer–Emmett–Teller (BET), and vibrating sample magnetometer (VSM) techniques. It was applied as an efficient and reusable catalyst for the synthesis of 2-(piperazin-1-yl) quinoxaline and benzimidazole derivatives via a one-pot multiple-component cascade reaction under green conditions. The results displayed the excellent catalytic activity of Fe3O4@PFBA–metformin@SO3H as an organic–inorganic hybrid nanocatalyst in condensation and multicomponent Mannich-type reactions. The easy separation, simple workup, excellent stability, and reusability of the nanocatalyst and quantitative yields of products and short reaction time are some outstanding advantages of this protocol.
- Esam, Zohreh,Akhavan, Malihe,Bekhradnia, Ahmadreza
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- Multifunctional quinoxaline-hydrazone derivatives with acetylcholinesterase and monoamine oxidases inhibitory activities as potential agents against Alzheimer’s disease
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Multitarget molecules are considered as an effective way for the treatment of AD, instead of the classic one-drug-one-target strategy because of the multifactorial nature of AD. A variety of studies indicate that several enzymes inhibitors can be useful in the treatment of AD, including acetylcholinesterase (AchE), butyrylcholinesterase (BuChE) and monoamine oxidase (MAO). Various substituted quinoxaline-hydrazone derivatives were synthesized, and their activity in vitro were investigated, including AChE/BuChE inhibitory activity and MAOA/B inhibitory activity. Based on the experimental results, compound 5l exhibited good inhibitory potency on both AchE (IC50 = 0.028 ± 0.001 μM) and monoamine oxidase B (IC50 = 0.046 ± 0.002 μM). Molecular modeling studies showed that 5l could bind to the active site of AChE and MAO-B. Taken together, these results suggested that compound 5l might be a potential multifunctional agent for the treatment of AD.
- Ilgin, Sinem,Karaduman, Abdullah Burak,Levent, Serkan,Osmaniye, Derya,?avu?o?lu, Betül Kaya,?evik, Ulviye Acar,?zkay, Yusuf,Kaplancikli, Zafer As?m,Karaburun, Ahmet ?a?r?,Sa?lik, Begüm Nurpelin,Turan, Gülhan
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p. 1000 - 1011
(2020/04/29)
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- Selective Halogenation of Pyridines Using Designed Phosphine Reagents
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Halopyridines are key building blocks for synthesizing pharmaceuticals, agrochemicals, and ligands for metal complexes, but strategies to selectively halogenate pyridine C-H precursors are lacking. We designed a set of heterocyclic phosphines that are installed at the 4-position of pyridines as phosphonium salts and then displaced with halide nucleophiles. A broad range of unactivated pyridines can be halogenated, and the method is viable for late-stage halogenation of complex pharmaceuticals. Computational studies indicate that C-halogen bond formation occurs via an SNAr pathway, and phosphine elimination is the rate-determining step. Steric interactions during C-P bond cleavage account for differences in reactivity between 2- and 3-substituted pyridines.
- Alegre-Requena, Juan V.,Levy, Jeffrey N.,Liu, Renrong,McNally, Andrew,Paton, Robert S.
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supporting information
p. 11295 - 11305
(2020/07/13)
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- Efficient Phosphorus-Free Chlorination of Hydroxy Aza-Arenes and Their Application in One-Pot Pharmaceutical Synthesis
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The chlorination of hydroxy aza-arenes with bis(trichloromethyl) carbonate (BTC) and SOCl2 has been effectively performed by refluxing with 5 wt % 4-dimethylaminopyridine (DMAP) as a catalyst. Various substrates are chlorinated with high yields. The obtained chlorinated aza-arenes can be used directly with simple workup for succedent one-pot synthesis on a large scale.
- Wang, Jian,Li, Yan-Hui,Pan, Song-Cheng,Li, Ming-Fang,Du, Wenting,Yin, Hong,Li, Jing-Hua
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supporting information
p. 146 - 153
(2020/03/10)
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- Design and synthesis of new quinoxaline derivatives as anticancer agents and apoptotic inducers
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The quinoxaline scaffold is a promising platform for the discovery of active chemotherapeutic agents. Three series of quinoxaline derivatives were synthesized and biologically evaluated against three tumor cell lines (HCT116 human colon carcinoma, HepG2, liver hepatocellular carcinoma and MCF-7, human breast adenocarcinoma cell line), in addition to VEGFR-2 enzyme inhibition activity. Compounds VIId, VIIIa, VIIIc, VIIIe and XVa exhibited promising activity against the tested cell lines and weak activity against VEGFR-2. Compound VIIIc induced a significant disruption in the cell cycle profile and cell cycle arrest at the G2/M phase boundary. In further assays, the cytotoxic effect of the highly active compounds was determined using a normal Caucasian fibroblast-like fetal lung cell line (WI-38). Compound VIIIc could be considered as a lead compound that merits further optimization and development as an anti-cancer and an apoptotic inducing candidate against the HCT116 cell line.
- El Newahie, Aliya M.S.,Nissan, Yassin M.,Ismail, Nasser S.M.,Abou El Ella, Dalal A.,Khojah, Sohair M.,Abouzid, Khaled A.M.
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- Quinoxaline-containing chalcone derivative and preparation method and application thereof
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The invention discloses a quinoxaline-containing chalcone derivative and a preparation method and application thereof. The general formula of the quinoxaline-containing chalcone derivative is shown inthe description, wherein X represents 2-O or 4-O, and R1 refers to a phenyl group, a heterocyclic group and one or more substituted phenyl groups with halogen at the 2nd-6th positions, C1-C6 alkyl atthe 2nd-6th positions, C1-C6 alkoxy at the 2nd-6th positions, nitro at the 2nd-6th positions, amino at the 2nd-6th positions and trifluoromethyl at the 2nd-6th positions; R2 represents one or more hydrogen atoms, C1-C6 alkoxy groups, nitro groups, C1-C6 alkyl groups and trifluoromethyl groups or halogen atoms at the 5th position, 6th position and 7th position or 8th position in a quinoxaline structure. The derivative can inhibit xanthomonas oryzae, xanthomonas citri and ralstonia solanacearum, raw materials are easily obtained, the reaction condition is mild, the post-treatment is simple, andthe yield is high.
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Paragraph 0028; 0030
(2019/06/30)
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- Quinoxaline-containing pentadiene ketone oxime ester compound and production method and application thereof
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The invention relates to a quinoxaline-containing pentadiene ketone oxime ester compound and a production method and application thereof. The compound is as shown in a formula A, wherein X is selectedfrom O, R1 is one of phenyl, substituted phenyl and substituted heterocyclyl, R2 is one of phenyl, substituted phenyl, substituted heterocyclyl and substituted benzyl, and R3 is a hydrogen atom or achlorine atom or the like. The compound has a good control effect on tobacco mosaic viruses.
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Paragraph 0071; 0076
(2019/10/01)
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- Antimicrobial evaluation and action mechanism of chalcone derivatives containing quinoxaline moiety
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Abstract: A series of chalcone derivatives containing quinoxaline moieties were synthesized, and their antibacterial activities were evaluated. Antibacterial bioassays indicated that some of the compounds exhibited significant antibacterial activity against Xanthomonas axonopodis pv. Citri (Xac), Xanthomonas oryzae pv. oryzae (Xoo), and Ralstonia solanacearum (Rs) at the concentrations of 50 or 100?μg/cm3. 50% effective concentration (EC50) values of (E)-3-(pyridin-2-yl)-1-[4-(quinoxalin-2-yloxy)phenyl]prop-2-en-1-one against Xac, Xoo, and Rs were 6.72, 15.17, and 9.29?μg/cm3, respectively, which were better than those of bismerthiazol (44.31, 42.46, and 62.36?μg/cm3, respectively). Scanning electron microscopy (SEM) was employed to analyze the mechanism of antibacterial action of that compound toward Xac. Graphical abstract: [Figure not available: see fulltext.].
- Xia, Rongjiao,Guo, Tao,He, Jun,Chen, Mei,Su, Shijun,Jiang, Shichun,Tang, Xu,Chen, Ying,Xue, Wei
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p. 1325 - 1334
(2019/07/03)
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- Quinoxaline-containing 1,4-pentadiene-3-one derivatives, and preparation method and application thereof
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The invention discloses quinoxaline-containing 1,4-pentadiene-3-one derivatives. The quinoxaline-containing 1,4-pentadiene-3-one derivatives are characterized by having a general formula which is as shown in the specification, wherein R1 is a phenyl, a substituted phenyl or a substituted aromatic heterocycle, and R2 one or more hydrogen atoms, methoxyls, nitryls, methyls, trifluoromethyls or halogen atoms contained on the 5-position, 6-position, 7-position and the 8-position of a quinoxaline structure. The compound provided by the invention has very good treating, protecting and passivating effects on TMV (Tobacco Mosaic Virus), shows high resistance to plant virus, and can be used for preparing a plant virus resisting pesticide.
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Paragraph 0043
(2018/03/28)
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- Quinoxaline-containing 1,4-pentadiene-3-ketones derivative, preparation method and application thereof
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The invention discloses a quinoxaline-containing 1,4-pentadiene-3-ketones derivative, a preparation method and an application thereof. The ketones derivative is as shown in the general structure (I) in the specification, wherein R1 is phenyl, substituted phenyl or substituted aromatic heterocyclic group; R is more than one hydrogen atom, methoxy group, nitro group, methyl group, trifluoromethyl group or halide atom on the 5,6,7 or 8 sites in the quinoxaline structure. The derivative has excellent inhibitory activity on liver cancer SMMC-7721 cells, shows relatively high anti-tumor activity andcan be used as a potential anti-tumor medicament.
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Paragraph 0015; 0017
(2018/10/11)
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- SELECTIVE KINASE INHIBITORS
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The present disclosure relates to methods of modulating (for example, inhibiting) activity of JAK3, comprising contacting the JAK3 with a compound of Formula I or pharmaceutically acceptable salt thereof, wherein constituent members are provided hereinwith. The present disclosure further provides novel compounds and compositions as well as their methods of preparation and use. The disclosed JAK3 inhibitors may be used in the treatment of JAK3-associated diseases including, for example, inflammatory and autoimmune disorders.
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Paragraph 0050; 0106; 0107
(2017/07/18)
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- A new solvent for the reaction of chlorination of hydroxyquinoxaline derivatives with vilsmeier reagent
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A new efficient procedure for the chlorination of hydroxyquinoxaline derivatives into the corresponding chlorides is described. It has been found that the use of 1-chlorobutane produces the highest yield, reduces the time of reaction and facilitates direct formation of crystals without any purification.
- Bouanane, Zohra,Bounekhel, Mahmoud,Elkolli, Meriem,Takfaoui, Abdelilah
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p. 903 - 906
(2018/04/09)
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- A highly practical and convenient halogenation of fused heterocyclic N-oxides
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A novel, simple and practical method for the regioselective halogenation of fused heterocyclic N-oxides has been developed. It employs Vilsmeier reagent, generated in situ by POX3and DMF, as both the activating agent and the nucleophilic halide source. The method is amenable across a broad range of substrates, including quinolines, isoquinolines and the diazine N-oxides, possessing a variety of substitution patterns. Furthermore, all of the reagents associated are cheap and easy to obtain. The potential extension of this method to a one-pot oxidation/halogenation sequence that obviates the need for isolation of the N-oxide intermediates is also presented.
- Wang, Dong,Wang, Yuxi,Zhao, Junjie,Li, Linna,Miao, Longfei,Wang, Dong,Sun, Hua,Yu, Peng
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p. 5762 - 5768
(2016/08/30)
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- N, N-disubstituted benzo-nitrogen heterocycles-2-amine compound and use thereof
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The invention mainly relates to an N,N-double substituted benzoazacyclo-2-amide compound and an application thereof. The N,N-double substituted benzoazacyclo-2-amide compound is a compound shown as formula I or a salt formed by a medical acid or alkali. The compound provided by the invention has strong inhibition activity on RhoA protease which is tightly related with cardiovascular and cerebrovascular diseases. The compound provided by the invention is hopeful to be developed into a RhoA protease small-molecule inhibitor type cardiovascular and cerebrovascular disease treatment medicine.
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Paragraph 0079-0082
(2016/10/09)
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- Development of second-generation small-molecule RhoA inhibitors with enhanced water solubility, tissue potency, and significant in vivo efficacy
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RhoA, a member of the Rho GTPases, is involved in a variety of cellular functions and could be a suitable therapeutic target for the treatment of cardiovascular diseases. However, few small-molecule RhoA inhibitors have been reported. Based on our previously reported lead compounds, 32 new 2-substituted quinoline (or quinoxaline) derivatives were synthesized and tested in biological assays. Six compounds showed high RhoA inhibitory activities, with IC50 values of 1.17-1.84 μM. Among these, (E)-3-(3-(ethyl(quinolin-2-yl)amino)phenyl)acrylic acid (26b) and (E)-3-(3-(butyl(quinolin-2-yl)amino)phenyl)acrylic acid (26d) demonstrated noticeable vasorelaxation effects against phenylephrine-induced contraction in thoracic aorta artery rings, and compound 26b had good water solubility and showed significant in vivo efficacy, which was similar to that of 5-(1,4-diazepane-1-sulfonyl)isoquinoline (fasudil) in a subarachnoid hemorrhage-cardiovascular model. To the best of our knowledge, compound 26b is the first example of a small-molecule RhoA inhibitor with potent in vivo efficacy, which could serve as a good lead for designing cardiovascular agents.
- Ma, Sheng,Deng, Jing,Li, Baoli,Li, Xiujiang,Yan, Zhaowei,Zhu, Jin,Chen, Gang,Wang, Zhong,Jiang, Hualiang,Miao, Liyan,Li, Jian
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p. 193 - 206
(2015/03/13)
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- Design, synthesis, and preliminary in vitro and in vivo pharmacological evaluation of 4-{4-[2-(4-(2-substitutedquinoxalin-3-yl)piperazin-1-yl)ethyl] phenyl}thiazoles as atypical antipsychotic agents
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A series of 4-{4-[2-(4-(2-substitutedquinoxalin-3-yl)piperazin-1-yl)ethyl] phenyl} thiazoles were synthesized in an effort to prepare novel atypical antipsychotic agents. The compounds were designed, synthesized, and characterized by spectral data (IR, 1H NMR, and MS) and the purity was ascertained by microanalysis. The D2 and 5-HT2A affinity of the synthesized compounds was screened in vitro by radioligand displacement assays on membrane homogenates isolated from rat striatum and rat cortex, respectively. Furthermore, all the synthesized final compounds (10a-g; 11a-g; 12a-g) were screened for their in vivo pharmacological activity in Swiss albino mice. D2 antagonism studies were performed using climbing mouse assay model and 5-HT2A antagonism studies were performed using quipazine-induced head twitches in mice. It was observed that none of the new chemical entities exhibited catalepsy and 12d, 11f, and 10a were found to be the most active compounds with 5-HT2A/D2 ratio of 1.23077, 1.14286, and 1.12857, respectively, while the standard drug risperidone exhibited 5-HT2A/D2 ratio of 1.0989. Among the twenty one new chemical entities, three compounds (12d, 11f, and 10a) were found to exhibit better atypical antipsychotic activity as they were found to have higher Meltzer index than the standard drug risperidone.
- Chandra Sekhar, Kondapalli Venkata Gowri,Rao, Vajja Sambasiva,Deuther-Conrad, Winnie,Sridhar, Divya,Nagesh, Hunsur Nagendra,Kumar, Vellas Sreedhar,Brust, Peter,Kumar, Muthyala Murali Krishna
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p. 1660 - 1673
(2013/07/26)
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- Phosphonium chloride as a non-volatile chlorinating reagent: Preparation and reaction in no solvent or ionic liquid
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Reaction of triphenylphosphine with trichloroisocyanuric acid in no solvent or an ionic liquid gave the corresponding phosphonium chloride, which can be used as a cheap and safe chlorinating reagent. Conversion of hydroxyheterocycles to chloroheterocycles, carboxylic acids to carboxylic acid chlorides, and primary amides to nitriles were accomplished by using the phosphonium chloride in excellent to good yields.
- Sugimoto, Osamu,Harada, Yukihiro,Tanji, Ken-Ichi
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p. 1583 - 1590
(2013/08/15)
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- Large-scale solvent-free chlorination of hydroxy-pyrimidines,-pyridines,- pyrazines and-amides using equimolar POCl3
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Chlorination with equimolar POCl3 can be efficiently achieved not only for hydroxypyrimidines, but also for many other substrates such as 2-hydroxy-pyridines,-quinoxalines, or even-amides. The procedure is solvent-free and involves heating in a sealed reactor at high temperatures using one equivalent of pyridine as base. It is suitable for large scale (multigram) batch preparations.
- Wang, Han,Wen, Kun,Wang, Le,Xiang, Ye,Xu, Xiaocheng,Shen, Yongjia,Sun, Zhihua
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experimental part
p. 4533 - 4544
(2012/06/30)
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- Design and synthesis of small molecule RhoA inhibitors: A new promising therapy for cardiovascular diseases?
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RhoA is a member of Rho GTPases, a subgroup of the Ras superfamily of small GTP-binding proteins. RhoA, as an important regulator of diverse cellular signaling pathways, plays significant roles in cytoskeletal organization, transcription, and cell-cycle progression. The RhoA/ROCK inhibitors have emerged as a new promising treatment for cardiovascular diseases. However, to date, RhoA inhibitors are macromolecules, and to our knowledge, small molecular-based inhibitors have not been reported. In this study, a series of first-in-class small molecular RhoA inhibitors have been discovered by using structure-based virtual screening in conjunction with chemical synthesis and bioassay. Virtual screening of ～200,000 compounds, followed by SPR-based binding affinity assays resulted in three compounds with binding affinities to RhoA at the micromolar level (compounds 1-3). Compound 1 was selected for further structure modifications in considering binding activity and synthesis ease. Fourty-one new compounds (1, 12a-v, 13a-h, and 14a-j) were designed and synthesized accordingly. It was found that eight (12a, 12j, 14a, 14b, 14d, 14e, 14 g, and 14h) showed high RhoA inhibition activities with IC50 values of 1.24 to 3.00 μM. A pharmacological assay indicated that two compounds (14g and 14 h) demonstrated noticeable vasorelaxation effects against PE-induced contraction in thoracic aorta artery rings and served as good leads for developing more potent cardiovascular agents.
- Deng, Jing,Feng, Enguang,Ma, Sheng,Zhang, Yan,Liu, Xiaofeng,Li, Honglin,Huang, Huang,Zhu, Jin,Zhu, Weiliang,Shen, Xu,Miao, Liyan,Liu, Hong,Jiang, Hualiang,Li, Jian
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experimental part
p. 4508 - 4522
(2011/09/14)
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- First synthesis of 2-phosphonylated quinoxaline 1,4-dioxides: An extension to the Beirut reaction
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An extension of the Beirut reaction for the preparation of the first members of the 2-phosphonylated quinoxaline 1,4-dioxide series is described. Contrary to their carboxylated equivalents, preparation of these new compounds could not be achieved under basic conditions but required the use of powdered molecular sieves. Good and reproducible yields were obtained only when the initial suspension in THF was transformed into a pasty film by slow evaporation of ca. 90% of the initial solvent volume.
- Dahbi, Samir,Methnani, Ebtissem,Bisseret, Philippe
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scheme or table
p. 5516 - 5520
(2010/10/21)
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- Pyrrolopyrrole cyanine dyes: A new class of near-Infrared dyes and fluorophores
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Pyrrolopyrrole cyanine (PPCy) dyes are presented as a novel class of near-infrared (NIR) chromophores, which are synthesized in a condensation reaction of diketopyrrolopyr-role with heteroarylacetonitrile compounds. Their optical properties are marked by strong and narrow-band NIR absorptions. Complexation prod-ucts with BF2 and BPh2 show strong NIR fluorescence and hardly any ab-sorption in the visible range. We syn-thesized a series of new PPCys that differ only in the heterocyclic peripheral groups of the chromophore. With this strategy, the absorption spectra can be tuned between 684 and 864 nm, while high fluorescence quantum yields are maintained. The influence of the heterocycle on the optical properties of the dyes is discussed.
- Fischer, Georg M.,Isomaki-Krondahl, Magnus,Gottker-Schnetmann, Inigo,Daltrozzo, Ewald,Zumbusch, Andreas
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supporting information; experimental part
p. 4857 - 4864
(2009/12/08)
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- Discovery of orally bioavailable and novel urea agonists of the high affinity niacin receptor GPR109A
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A urea class of high affinity niacin receptor agonists was discovered. Compound 1a displayed good PK, better in vivo efficacy in reducing FFA in mouse than niacin, and no vasodilation in a mouse model. Compound 1q demonstrated equal affinity to GPR109A as niacin.
- Shen, Hong C.,Szymonifka, Michael J.,Kharbanda, Divya,Deng, Qiaolin,Carballo-Jane, Ester,Wu, Kenneth K.,Wu, Tsuei-Ju,Cheng, Kang,Ren, Ning,Cai, Tian-Quan,Taggart, Andrew K.,Wang, Junying,Tong, Xinchun,Waters, M. Gerard,Hammond, Milton L.,Tata, James R.,Colletti, Steven L.
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p. 6723 - 6728
(2008/04/03)
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- Solvent-free reaction using phosphonium salts: Chlorination of hydroxyheteroaromatics and dehydration of primary amides
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Solvent-free chlorination of heteroaromatics using the phosphonium salt, prepared by reaction of triphenylphosphine with N-chlorosuccinimide, was accomplished by microwave-irradiation or heating to give the corresponding chloroheteroaromatics. Similarly, primary amides was converted into nitriles by this method.{A figure is presented}.
- Takahashi, Tatsuya,Sugimoto, Osamu,Koshio, Jiro,Tanji, Ken-ichi
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p. 1973 - 1979
(2007/10/03)
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- Microwave-assisted dehydration and chlorination using phosphonium salt
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Microwave-assisted reaction using phosphonium salt for dehydration of primary amides and chlorination of hydroxyheteroaromatics was carried out. Copyright Taylor & Francis, Inc.
- Tanji, Ken-Ichi,Koshio, Jiro,Sugimoto, Osamu
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p. 1983 - 1987
(2007/10/03)
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- Preparation of nitrogen-containing π-deficient heteroaromatic Grignard reagents: Oxidative magnesiation of nitrogen-containing π-deficient halogenoheteroaromatics using active magnesium
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The oxidative magnesiation of nitrogen-containing π-deficient halogenoheteroaromatics using active magnesium was accomplished. Both magnesiation followed by addition of a carbonyl compound (Grignard reaction) and magnesiation in the presence of a carbonyl compound (Barbier reaction) were carried out to afford the corresponding product. Especially, the latter method enabled fused halogenodiazines such as 4-chloro-1-phenyl-1H-pyrazolo[3,4-d]pyrimidine or 2-chloroquinoxaline to magnesiate at a mild temperature (-20 to 30 °C).
- Sugimoto, Osamu,Yamada, Shigeru,Tanji, Ken-Ichi
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p. 2054 - 2057
(2007/10/03)
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- Application of phosphonium salts to the reactions of various kinds of amides
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The phosphonium salts 1 and 2 prepared from triphenylphosphine and N-halogenosuccinimide proved to be applicable to the conversion of amide compounds. Especially, halogenation of electron-deficient heteroaromatic alcohols with these reagents seems to be a convenient method compared to the halogenation with phosphorus oxyhalides.
- Sugimoto, Osamu,Mori, Miho,Moriya, Keisuke,Tanji, Ken-Ichi
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p. 1112 - 1118
(2007/10/03)
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- A facile halogenation of some hydroxyheterocycles using triphenylphosphine and N-halosuccinimide
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Some hydroxyheterocycles were halogenated to give the corresponding haloheterocycles using triphenylphosphine and N-halosuccinimide. In comparison with the usual method using phosphorus oxyhalide, the haloheterocycles were easily isolated.
- Sugimoto, Osamu,Mori, Miho,Tanji, Ken-ichi
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p. 7477 - 7478
(2007/10/03)
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- UNPRODUCTIVE SIGMA AND PI COMPLEXES IN THE REACTION OF 2-CHLOROQUINOXALINE WITH PIPERIDINE IN DIMETHYL SULPHOXIDE
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The rate of the reaction of 2-chloroquinoxaline with piperidine in dimethyl sulphoxide was measured over a wide range of amine concentrations and at several temperatures.It was found that the order with respect to the nucleophile is close to 1 between 300 and 320 K, but is definitely less at lower and higher temperatures.It is suggested that below 300 K an unreactive charge-transfer complex is formed between the reactants which dissociates at higher temperatures, whereas at temperatures higher than 320 K an unproductive ? complex is formed, the concentration of which increases with increase in temperature.
- Nasielski, J.,Rypens, C.
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p. 545 - 550
(2007/10/02)
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- AN UNEXPECTED RING-OPENING IN THE REISSERT REACTION ON 2,3-DIPHENYLQUINOXALINE-N-OXIDE.
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When quinoxaline-N-oxide 1 is reacted with KCN and benzoyl chloride in water (the Reissert reaction) or methanol, the products are 2-, 5- and 6- chloroquinoxaline (the latter being the major product: 42+/-6percent) and small amounts of 2-cyanoquinoxaline.Using three equivalents of trimethylsilyl cyanide instead of KCN, and dichloromethane as the solvent, leads to a 72percent yield of 2-cyanoquinoxaline.The reaction of trimethylsilyl cyanide and benzoyl chloride with 2,3-diphenylquinoxaline-N-oxide 2 leads to an unexpected ring-opening product 13; its structure is based on spectroscopic data and on an X-ray crystallographic analysis.
- Nasielski, J.,Heilporn, S.,Nasielski-Hinkens, R.,Tinant, B.,Declercq, J. P.
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p. 7795 - 7804
(2007/10/02)
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- PHOTODECARBOXYLATIVE CHLORINATION OF CARBOXYLIC ACIDS VIA THEIR BENZOPHENONE OXIME ESTERS
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Decarboxylative chlorination of various aromatic and aliphatic carboxylic acids is performed successfully by the photolysis of their benzophenone oxime esters in carbon tetrachloride and corresponding chloro compounds are prepared in good yields.High selective generation of the certain radical and efficiency of the stable radical precursor, benzophenone oxime ester, afford much advantage for radical chemistry.
- Hasebe, Masato,Tsuchiya, Takashi
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p. 6287 - 6290
(2007/10/02)
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- FACILE SYNTHESIS AND HERBICIDAL ACTIVITIES OF NOVEL FLUOROQUINOXALINES
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The synthesis of new 2-fluoro-, 3-fluoro- and 2,3-difluoroquinoxalines by nucleophilic substitution with cesium fluoride as coupled with 18-crown-6 and their herbicidal activities are described.
- Makino, Kenzi,Yoshioka, Hirosuke
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p. 1215 - 1220
(2007/10/02)
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- REGIOSELECTIVITY IN THE REACTION OF NITROQUINOXALINE-N-OXIDES WITH PHOSPHORYL CHLORIDE
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6-nitro-, 2-methyl-6-nitro- and 2,3-dimethyl-6-nitroquinoxaline have been transformed into their N-oxides by MCPBA in chloroform; the nitro group orients the oxygen atom preferentially to nitrogen atom N1, but the N4:N1 selectivity is diminished in the methylated derivatives.Under the action of POCl3 (the Meisenheimer reaction), the N-oxides of the unmethylated compounds are transformed into chloro-nitroquinoxalines having lost the N-oxide oxygen atom.The orientation of the entering chloride ion is discussed on the basis of electronic effects induced by the N-oxide and nitro groups, and it is suggested that the last step, the elimination of "HPO2Cl2" is a concerted process.
- Nasielski-Hinkens, R.,Vyver, E. Vande,Nasielski, J.
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p. 663 - 670
(2007/10/02)
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- THE SYNTHESES OF NOVEL 2-(2-QUINOXALINYL)PYRIDAZIN-3(2H)-ONES
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The first syntheses of 4-chloro-2-(2-quinoxalinyl)-pyridazin-3(2H)-one derivatives are reported.They could be synthesized from 2-hydrazinoquinoxaline derivatives as starting materials.
- Makino, Kenzi,Sakata, Gozyo
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p. 2603 - 2611
(2007/10/02)
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- REGIOSELECTIVE SYNTHESIS OF 2,6-DICHLOROQUINOXALINE AND 2-CHLORO-6-IODOQUINOXALINE
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Facile regioselective synthesis of 2,6-dichloroquinoxaline and 2-chloro-6-iodoquinoxaline is described.Electrophilic substitution reaction of 2(1H)-quinoxalinone with chloride and iodide ion in 95percent sulfuric acid occurred at 6-position exclusively.
- Sakata, Gozyo,Makino, Kenzi
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p. 323 - 326
(2007/10/02)
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- OXIDATION OF SOME HETARYLHYDRAZINES WITH SELENIUM DIOXIDE
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The oxidation of 2-benzimidazolyl- and 2-quinoxalinylhydrazines with selenium dioxide in hydrochloric acid in the presence of cuprous chloride leads to the formation of 2-chloro derivatives of the heterocycles.When the reaction is carried out in ethanol, 2-benzimidazolylhydrazines give symmetrical formazans.In both cases oxidation proceeds through a step involving the formation of hetarenediazonium salts.
- Sedov, Yu. A.
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p. 217 - 220
(2007/10/02)
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- O-Alkyl-S-[3-oxo-1,2,4-triazolobenzopyrazin(2)yl-methyl]-(thiono)thiolphosphoric(phosphonic) acid esters
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O-Alkyl-S-[3-oxo-1,2,4-triazolobenzopyrazin(2)yl-methyl]-(thiono)thiolphosphoric(phosphonic) acid esters of the formula STR1 in which R is alkyl with 1 to 4 carbon atoms, R1 is alkyl or alkoxy with 1 to 4 carbon atoms, and X is oxygen or sulfur, Which possess insecticidal properties.
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