- Synthetic method of active intermediate 4-chloro-3-nitropyridine
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The invention discloses a synthetic method of active intermediate 4-chloro-3-nitropyridine. The method comprises the following steps: step 1, adding 24L of concentrated sulfuric acid into a 50L reaction kettle, cooling to about 10 DEG C, adding 4kg of raw materials in batches, carrying out HPLC detection on the end of the reaction of the raw materials on the next day, carrying out aftertreatment, slowly pouring the reaction liquid into 30L of ice water for quenching, adjusting the pH value to 7, carrying out suction filtration to obtain a faint yellow solid, and carrying out suction filtration; drying to obtain 4.6 kg of 4-hydroxy-3-nitropyridine faint yellow solid with the yield of 80% and the purity of 98%; and 2, adding 500g of SM into a 10L reaction flask at room temperature, dissolving with 5L of methylbenzene, dropwise adding 1643g of phosphorus oxychloride at room temperature, dropwise adding the crude product into PE, stirring and extracting for multiple times to obtain 388g of 4-chloro-3-nitropyridine faint yellow solid with the yield of 68% and the purity of 95%. According to the synthetic method of active intermediate 4-chloro-3-nitropyridine, improvement points of the project process mainly aim at purity control and reaction stability control of the reaction in the third step, aftertreatment is simple, and product purification can be achieved through extraction.
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Paragraph 0013; 0019; 0025
(2021/04/28)
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- Second generation of diazachrysenes: Protection of Ebola virus infected mice and mechanism of action
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Ebola virus (EBOV) causes a deadly hemorrhagic fever in humans and non-human primates. There is currently no FDA-approved vaccine or medication to counter this disease. Here, we report on the design, synthesis and anti-viral activities of two classes of compounds which show high potency against EBOV in both in vitro cell culture assays and in vivo mouse models Ebola viral disease. These compounds incorporate the structural features of cationic amphiphilic drugs (CAD), i.e they possess both a hydrophobic domain and a hydrophilic domain consisting of an ionizable amine functional group. These structural features enable easily diffusion into cells but once inside an acidic compartment their amine groups became protonated, ionized and remain trapped inside the acidic compartments such as late endosomes and lysosomes. These compounds, by virtue of their lysomotrophic functions, blocked EBOV entry. However, unlike other drugs containing a CAD moiety including chloroquine and amodiaquine, compounds reported in this study display faster kinetics of accumulation in the lysosomes, robust expansion of late endosome/lysosomes, relatively more potent suppression of lysosome fusion with other vesicular compartments and inhibition of cathepsins activities, all of which play a vital role in anti-EBOV activity. Furthermore, the diazachrysene 2 (ZSML08) that showed most potent activity against EBOV in in vitro cell culture assays also showed significant survival benefit with 100% protection in mouse models of Ebola virus disease, at a low dose of 10 mg/kg/day. Lastly, toxicity studies in vivo using zebrafish models suggest no developmental defects or toxicity associated with these compounds. Overall, these studies describe two new pharmacophores that by virtue of being potent lysosomotrophs, display potent anti-EBOV activities both in vitro and in vivo animal models of EBOV disease.
- Selakovi?, ?ivota,Tran, Julie P.,Kota, Krishna P.,Lazi?, Marija,Retterer, Cary,Besh, Robert,Panchal, Rekha G.,Soloveva, Veronica,Sean, Vantongreen A.,Jay, Wells B.,Pavi?, Aleksandar,Verbi?, Tatjana,Vasiljevi?, Branka,Kuehl, Kathleen,Duplantier, Allen J.,Bavari, Sina,Mudhasani, Rajini,?olaja, Bogdan A.
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supporting information
p. 32 - 50
(2018/11/21)
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- 4-chloro-3-nitropyridine and preparation method thereof
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The invention discloses 4-chloro-3-nitropyridine and a preparation method thereof. The preparation method is characterized in that 4-hydroxypyridine is taken as the raw material, ionic liquid is taken as a reaction medium and mesoporous silica is taken as a catalyst, and comprises the following steps: firstly, carrying out nitration reaction with nitric acid to produce 4-hydroxyl-3-nitropyridine; carrying out reaction between 4-hydroxyl-3-nitropyridine and phosphorus oxychloride under catalyzation of thionyl chloride to produce 4-chloro-3-nitropyridine. According to 4-chloro-3-nitropyridine and the preparation method thereof provided by the invention, the condition is mild and easy to control, the requirement on equipment is low, the product purity is high, and the yield is high.
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Paragraph 0020; 0021
(2016/11/17)
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- High colour rendering index and colour stable hybrid white efficient OLEDs with a double emitting layer structure using a single phosphorescence dopant of heteroleptic platinum complexes
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Four heteroleptic platinum complexes (FPtXND) bearing 4-hydroxy-1,5-naphthyridine derivatives functionalized with dimethyl (X = mm), phenoxy (X = OPh), piperidine (X = pp), or carbazole (X = Cz) units as one ligand (XND) and 2-(2,4-difluorophenyl)pyridine as the other common ligand (F) were newly synthesized and characterized. The crystal structures of FPtOPhND and FPtCzND were determined by single-crystal X-ray diffraction crystallography. Although they have a short plane-to-plane packing distance of 3.62 and 3.39 A, respectively, both platinum complexes have different molecular packing patterns, which affect their photoluminescence (PL) in solution and electroluminescence (EL) in the solid state. Due to the contribution from both monomers and excimers/aggregates, all of the platinum complexes exhibited broad and red-shifted PL in concentrated solutions as well as in doped thin films. In the monochromatic organic lighting diode (OLED) testing, FPtXND doped in 4,4′-di(9H-carbazol-9-yl)-1,1′-biphenyl (CBP) exhibited greenish yellow or orange yellow EL, of which FPtOPhND has the highest EL efficiency mainly due to its high solution PL quantum yield of 21%. Hybrid white OLEDs were first achieved with a single emitting layer configuration, of which highly fluorescent blue N,N′-di-1-naphthalenyl-N,N′-diphenyl-[1,1′:4′,1″:4″,1-quaterphenyl]-4,4-diamine (4P-NPD) was used as the host material for all four platinum complexes. To improve the performance of the FPtOPhND-based hybrid white OLEDs, double emitting layer configurations were adopted with CBP and 4P-NPD as the host material. Virtually voltage independent, a white EL having CIEx,y (0.33, 0.31) and a CRI as high as 91 was obtained. The maximum EL efficiency of 11.8%, 25.9 cd A-1, or 11.6 lm W-1 was acquired with FPtOPhND doped in the double emitting layer configuration of an OLED.
- Poloek, Anurachw,Lin, Chiao-Wen,Chen, Chin-Ti,Chen, Chao-Tsen
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p. 10343 - 10356
(2015/02/19)
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- Manganese salen complexes with acid-base catalytic auxiliary: Functional mimetics of catalase
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Antioxidant therapies have been considered for a wide variety of disorders associated with oxidative stress, and synthetic catalytic scavengers of reactive oxygen species would be clinically superior to stoichiometric ones. Among them, salen-manganese complexes (Mn(Salen)) seem promising, because they exhibit dual functions, i.e. superoxide dismutase- and catalase-mimetic activities. We have been developing enzyme-mimetic Mn(Salen) complexes bearing a functional group that enhances their catalytic activity. Here, we describe the design and synthesis of novel Mn(Salen) complexes with general acid-base catalytic functionality, inspired by the reaction mechanism of catalase. As expected, these Mn(Salen) complexes showed superior catalase-like activity and selectivity, while retaining moderate SOD-like activity. An unsubstituted pyridyl group worked well as a functionality to promote catalase-like activity. The introduced functionality did not alter the redox potential suggesting that the auxiliary-modified complex acted as an acid-base catalyst analogous to catalase. We believe that our approach provides a new design principle for sophisticated catalyst design. Further, the compounds described here appear to be good candidates for use in antioxidant therapy.
- Noritake, Yukinobu,Umezawa, Naoki,Kato, Nobuki,Higuchi, Tsunehiko
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p. 3653 - 3662
(2013/05/09)
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- Use of the graebe-ullmann reaction in the synthesis of 8-methyl-γ- carboline and isomeric aromatic aza-γ-carbolines
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Two variants of the Graebe-Ullmann reaction were used to obtain 8-methyl-5H-pyrido[4,3-b]indole (8-methyl-γ-carboline) and the conditions for this reaction were optimized. The feasibility of using this method was studied for the synthesis of a series of isomeric aromatic aza-γ- carbolines from the corresponding 1-(pyridyl)-1H-1,2,3-triazolo[4,5-c]pyridines under thermal and microwave irradiation conditions.
- Alekseev,Kurkin,Yurovskaya
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p. 1235 - 1250
(2013/03/13)
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- Novel multifunctional organic semiconductor materials based on 4,8-substituted 1,5-naphthyridine: Synthesis, single crystal structures, opto-electrical properties and quantum chemistry calculation
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A series of 4,8-substituted 1,5-naphthyridines (1a-1h) have been successfully synthesised by a Suzuki cross-coupling between 4,8-dibromo-1,5- naphthyridine (4) and the corresponding boronic acids (2a-2h) in the presence of catalytic palladium acetate in yields of 41.4-75.8% and have ben well characterized. They are thermally robust with high phase transition temperatures (above 186 °C). Compounds 1b, 1e and 1f crystallized in the monoclinic crystal system with the space groups P21/c, P21/c and P21/n, respectively. All of them show the lowest energy absorption bands (λmaxAbs: 294-320 nm), revealing low optical band gaps (2.77-3.79 eV). These materials emit blue fluorescence with λmaxEm ranging from 434-521 nm in dilute solution in dichloromethane and 400-501 nm in the solid state. 4,8-Substituted 1,5-naphthyridines 1a-1h have estimated electron affinities (EA) of (2.38-2.72 eV) suitable for electron-transport materials and ionization potentials (IP) of 4.85-5.04 eV facilitate excellent hole-injecting/hole-transport materials properties. Quantum chemical calculations using DFT B3LYP/6-31G* showed nearly identical the lowest unoccupied molecular orbitals (LUMO) of -2.39 to -2.19 eV and the highest occupied molecular orbitals (HOMO) of -5.33 to -6.84 eV. These results demonstrate the 4,8-substituted 1,5-naphthyridines 1a-1h with a simple architecture might be promising blue-emitting (or blue-green-emitting) materials, electron-transport materials and hole-injecting/hole-transport materials for applications for developing high-efficiency OLEDs.
- Wang, Kun-Yan,Chen, Chen,Liu, Jin-Fang,Wang, Qin,Chang, Jin,Zhu, Hong-Jun,Li, Chong
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scheme or table
p. 6693 - 6704
(2012/09/22)
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- Preparation of azaindolines and benzoyl substituted azaindolines: Precursors of triazabenzo[cd]azulen-9-one PDE4 inhibitors
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The syntheses of various substituted azaindolines are described. Azaindolines were identified as potential key intermediates towards new PDE4 inhibitors.
- Badland, Matthew,Devillers, Ingrid,Durand, Corinne,Fasquelle, Véronique,Gaudillire, Bernard,Jacobelli, Henry,Manage, Ajith C.,Pevet, Isabelle,Puaud, Jocelyne,Shorter, Anthony J.,Wrigglesworth, Roger
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supporting information; experimental part
p. 5292 - 5296
(2011/10/30)
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- Thiazole[4,5-C]pyridine derivatives
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The invention relates to compounds of general formula I: wherein R1, R2 and R3 are as defined in the description such compounds are metabotropic glutamate receptor antagonists and are useful in the treatment or prevention of mGluR5 receptor mediated disorders.
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Page/Page column 9-10
(2008/06/13)
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- INDAZOLECARBOXAMIDE DERIVATIVES FOR THE TREATMENT AND PREVENTION OF MALARIA
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The invention relates to methods of treating or preventing malaria which comprises administering to a patient in need thereof, an effective amount of a 1H-indazole-3-carboxamide derivative of general formula (I), in the form of a base or of an addition salt with an acid, or in the form of a hydrate or of a solvate of said base or acid addition salt.
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Page/Page column 11
(2010/11/28)
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- Foldamer-based pyridine-fullerene tweezer receptors for enhanced binding of zinc porphyrin
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This paper reports the design and synthesis of a new series of hydrogen bonding-mediated foldamer-derived tweezer receptors that are used for efficient complexation of zinc porphyrin guest. One end of the rigidified aromatic amide backbone is incorporated with one fullerene unit, while another end is connected to one pyridine or imidazole unit. The 1H NMR, UV-vis, and fluorescent investigations in chloroform revealed that, due to the intramolecular hydrogen bonding-driven preorganized folded conformation, the fullerene and pyridine units of the receptors are located with suitable spatial separation and consequently able to co-complex zinc porphyrin with remarkably increased stability. In contrast, the imidazole-incorporated receptor displays a weakened binding affinity possibly due to structural mismatching and large steric hindrance. The association constants of the complexes of the new receptors with zinc porphyrin have been determined.
- Wu, Zong-Quan,Li, Chang-Zhi,Feng, Dai-Jun,Jiang, Xi-Kui,Li, Zhan-Ting
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p. 11054 - 11062
(2007/10/03)
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- Indazolecarboxamide derivatives, preparation and use thereof as CDK1, CDK2 and CDK4 inhibitors
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Compound corresponding to general formula (I): [image] in which, R1 represents a hydrogen or halogen atom, an NH2, NHR2, NHCOR2, NO2, CN, CH2NH2 and CH2NHR2; or alternatively R1 represents an optionally substituted phenyl or an optionally substituted heteroaromatic group; Ar represents an optionally substituted phenyl group or an optionally substituted heteroaromatic group; n represents 0, 1, 2 or 3; in the form of a base, of an addition salt with an acid, of a hydrate or of a solvate. Application in therapy.
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Page/Page column 24
(2008/06/13)
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- Development of an efficient and scalable process of a respiratory syncytial virus inhibitor
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An improved process has been developed for compound 1, a respiratory syncytial virus (RSV) inhibitor. This improved process is convergent, safe, efficient, and useful to prepare compound 1 in kilogram quantities.
- Provencal, David P.,Gesenberg, Kirsten D.,Wang, Hua,Escobar, Carlos,Wong, Henry,Brown, Matthew A.,Staab, Andrew J.,Pendri, Yadagiri R.
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p. 903 - 908
(2013/09/03)
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- IL-8 receptor antagonists
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The present invention relates to the use of phenyl ureas in the treatment of disease states mediated by the chemokine, Interleukin-8 (IL-8).
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- Cross coupling strategies towards the synthesis of the streptonigrin CD moiety
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An efficient route to an appropriate model of the streptonigrin 4- phenylpyridine CD moiety is reported. 4-Chloro-3-nitropyridine was found to be the key precursor and its reactivity in cross coupling reactions was further investigated.
- Crous, Renier,Dwyer, Catherine,Holzapfel, Cedric W.
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p. 721 - 726
(2007/10/03)
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- Pyrido[3,4-e]-1,2,4-triazines and related heterocycles as potential antifungal agents
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The preparation and biological activities of a series of pyrido[3,4-e]-1,2,4-triazines, 1,2,4-triazino[5,6-c]quinolines, and related fused triazines are described. Methyl, amino, and acylamino substituents were placed in the pyridyl ring of the former system. Other structural modifications included various alkyl, cycloalkyl, substituted phenyl, and heterocyclic groups in the 3-position of these ring systems. In agar dilution assays, actives in this series inhibited strains of Candida, Aspergillus, Mucor, and Trychophyton species at MIC's of ≤ 16 μg/mL.
- Reich,Fabio,Lee,Kuck,Testa
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p. 2474 - 2485
(2007/10/02)
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- Potential inhibitors of S-adenosylmethionine-dependent methyltransferases. 8. Molecular dissections of carbocyclic 3-deazaadenosine as inhibitors of S-adenosylhomocysteine hydrolase
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A series of 9-(hydroxyalkyl)-3-deazaadenines, which are analogues of the carbocyclic derivative of 3-deazaadenosine (3-deaza-C-Adpo), were synthesized. The analogues were tested as inhibitors of bovine liver S-adenosyl-L-homocysteine (AdoHcy) hydrolase (EC 3.3.1.1) and as inhibitors of vaccinia virus (WR) replication in clone 929 mouse L cells and the results were compared to those observed for the parent compound, 3-deaza-C-Ado. 4-Amino-1-(2,3-dihydroxy-1-propyl)imidazo[4,5-c]pyridine (14), the analogue which included the 1'-, 2'- and 3'-carbons of 3-deaza-C-Ado, was the most active inhibitor toward purified AdoHcy hydrolase. The inhibitory effect of 14 (K(i) = 768 nM) on AdoHcy hydrolase was significantly less than that observed for 3-deaza-C-Ado (K(i) = 4 nM). Analogue 14 also exhibited inhibitory activity against vaccinia virus replication, but the activity was less than that observed with 3-deaza-C-Ado. 4-Amino-1-(4-hydroxy-1-butyl)imidazo[4,5-c]pyridine (15) showed little or no inhibitory activity toward AdoHcY hydrolase, but it did exhibit antiviral effects comparable to 14. These results suggest that 3-deaza-C-Ado and analogue 14 may be producing their antiviral effects by altering a critical viral methylation (e.g., methylation of the 5'-cap of viral mRNA), whereas analogue 15 may be acting through an alternative mechanism.
- Houston,Dolence,Keller,Patel-Thombre,Borchardt
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p. 467 - 471
(2007/10/02)
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- NUCLEOPHILIC SUBSTITUTION IN o-NITROAZIDES OF THE PYRIDINE SERIES
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The reactions of 2-nitro-3-azidopyridine and 3-nitro-4-azidopyridine with amines and anionic nucleophiles, viz., sodium hydroxide, sodium alkoxides, the sodium salt of p-thiocresol, and potassium cyanide, were investigated.A possible reaction mechanism is proposed.
- Kotovskaya, S. A.,Mokrushina, G. A.,Postovskii, I. Ya.
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p. 303 - 306
(2007/10/02)
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- Dipyrido [4,3-b] [3,4-f] indoles and process for obtaining them
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The invention relates to compounds of formula: STR1 wherein R'1 =H, OH or an alkyl group, preferably a lower alkyl group, alkylthio or alkoxy, an halogen or an amino group, R'2 =H or a lower alkyl group. These compounds have antitumoral and antiviral properties useful for the treatment of cancers.
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