- Concise synthesis of 12a-methyl-11-aryl-1,2-dihydrobenzo[f]pyrrolo[1,2-a]quinolin-3(12aH)-ones as racemic 14-azaestrogen analogs
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A concise method for the synthesis of 14-azasteroid analogs with angular methyl group at C-13 of the steroidal nucleus has been reported in this paper. We have developed an interesting cascade reaction of arylacetylenes and N-(naphthalen-2-yl)pent-4-ynamides under gold (III)-catalysis to produce novel tetracyclic 12a-methyl-11-aryl-1,2-dihydrobenzo[f]pyrrolo[1,2-a]quinolin-3(12aH)-ones which may be viewed as 14-azaestrogen analogs.
- Abdelkhalik, Ashraf M.,Paul, Nawal K.,Jha, Amitabh
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Read Online
- Organic electroluminescent compounds and organic electroluminescent device using the same
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The present invention relates to an organic electroluminescent compound applied to a hole transfer material, which is characterized by being presented by chemical formula 1-1 and chemical formula 1-2. The organic electroluminescent compound according to the present invention can manufacture an organic electroluminescent device having improved light emitting efficiency and life properties, when applied to a hole transfer layer of the organic electroluminescent device.
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Paragraph 0408-0413
(2020/12/15)
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- Enantioselective Construction of Axially Chiral Amino Sulfide Vinyl Arenes by Chiral Sulfide-Catalyzed Electrophilic Carbothiolation of Alkynes
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The enantioselective construction of axially chiral compounds by electrophilic carbothiolation of alkynes is disclosed for the first time. This enantioselective transformation is enabled by the use of a Ts-protected bifunctional sulfide catalyst and Ms-protected ortho-alkynylaryl amines (Ts=tosyl; Ms=mesyl). Both electrophilic arylthiolating and electrophilic trifluoromethylthiolating reagents are suitable for this reaction. The obtained products of axially chiral vinyl–aryl amino sulfides can be easily converted into biaryl amino sulfides, biaryl amino sulfoxides, biaryl amines, vinyl–aryl amines, and other valuable difunctionalized compounds.
- Ji, Jieying,Jiang, Quanbin,Liang, Yaoyu,Luo, Jie,Zhang, Xiaoyan,Zhao, Xiaodan
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supporting information
p. 4959 - 4964
(2020/02/11)
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- Discovery and Development of Metal-Catalyzed Coupling Reactions in the Synthesis of Dasabuvir, an HCV-Polymerase Inhibitor
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Dasabuvir (1) is an HCV polymerase inhibitor which has been developed as a part of a three-component direct-acting antiviral combination therapy. During the course of the development of the synthetic route, two novel coupling reactions were developed. First, the copper-catalyzed coupling of uracil with aryl iodides, employing picolinamide 16 as the ligand, was discovered. Later, the palladium-catalyzed sulfonamidation of aryl nonaflate 33 was developed, promoted by electron-rich palladium complexes, including the novel phosphine ligand, VincePhos (50). This made possible a convergent, highly efficient synthesis of dasabuvir that significantly reduced the mutagenic impurity burden of the process.
- Barnes, David M.,Shekhar, Shashank,Dunn, Travis B.,Barkalow, Jufang H.,Chan, Vincent S.,Franczyk, Thaddeus S.,Haight, Anthony R.,Hengeveld, John E.,Kolaczkowski, Lawrence,Kotecki, Brian J.,Liang, Guangxin,Marek, James C.,McLaughlin, Maureen A.,Montavon, Donna K.,Napier, James J.
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p. 4873 - 4892
(2019/02/05)
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- 6-bromo-2-aminonaphthalene preparation method
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The invention provides a 6-bromo-2-aminonaphthalene preparation method. According to the present invention, the easily-available and inexpensive starting materials such as 2-aminonaphthalene, bromine,di-tert-butyl dicarbonate and the like are used; most of the intermediates are not required to be purified and directly enter the next step so as to substantially improve the consistency of the process; the high temperature and high pressure special reaction is not used so as to reduce the production risks; the yields of each reaction are high while the quality of the product meets the requirement; the amount of the three-waste is low so as to reduce the environmental protection pressure of the factory and meet the national conditions; and the product is refined by using the slat forming method so as to substantially improve the purity of the product.
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Paragraph 0041; 0046; 0047; 0076; 0077; 0078; 0079-0081
(2019/01/08)
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- A N, N - diaryl - 2 - bromo - 6 - naphthylamine synthetic method and its application
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The invention discloses a synthetic method of N, N-diaryl-2-bromine-6-naphthylamine. The synthetic method comprises the step of carrying out C-N coupled reaction on halogenated arene and a 6-bromine-2-naphthylamine unit to obtain an N, N-diaryl-2-bromine-6-naphthylamine unit. The invention also discloses application of N, N-diaryl-2-bromine-6-naphthylamine, namely, N, N-diaryl-2-bromine-6-naphthylamine provided by the invention is adopted as the raw material to prepare an organic semiconductor material; compared with the conventional synthetic method, the synthetic method of N, N-diaryl-2-bromine-6-naphthylamine provided by the invention is simple in synthetic route and high in comprehensive yield; the organic semiconductor material which contains a diaryl naphthyl amine functional unit and is prepared from N, N-diaryl-2-bromine-6-naphthylamine provided by the invention is relatively high in hole mobility and thin film morphology stability.
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Paragraph 0081; 0082; 0102
(2017/12/01)
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- Discovery of potent macrocyclic HCV NS5A inhibitors
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HCV NS5A inhibitors have demonstrated impressive in vitro virologic profiles in HCV replicon assays and robust HCV RNA titer reduction in the clinic making them attractive components for inclusion in an all oral fixed-dose combination (FDC) regimen for the treatment of HCV infection. Merck's effort in this area identified MK-4882 and MK-8325 as early development leads. Herein, we describe the discovery of potent macrocyclic NS5A inhibitors bearing the MK-8325 or MK-4882 core structure.
- Yu, Wensheng,Vibulbhan, Bancha,Rosenblum, Stuart B.,Martin, Gregory S.,Vellekoop, A. Samuel,Holst, Christian L.,Coburn, Craig A.,Wong, Michael,Selyutin, Oleg,Ji, Tao,Zhong, Bin,Hu, Bin,Chen, Lei,Dwyer, Michael P.,Jiang, Yueheng,Nair, Anilkumar G.,Tong, Ling,Zeng, Qingbei,Agrawal, Sony,Carr, Donna,Rokosz, Laura,Liu, Rong,Curry, Stephanie,McMonagle, Patricia,Ingravallo, Paul,Lahser, Fred,Asante-Appiah, Ernest,Fells, James,Kozlowski, Joseph A.
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p. 3793 - 3799
(2016/07/21)
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- Substituted benzoquinazolinones. Part 2: Synthesis of amino-, and sulfanyl-derivatives of benzo[f]- and benzo[h]quinazolinones
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Amino- and sulfanyl-derivatives of benzoquinazolinones 16a-c, 20a-c and 21a-c were prepared under palladium-catalyzed Buchwald-Hartwig coupling reaction using bromobenzoquinazolinones 15, 19a, 19b and 1-substituted piperazines or mercaptans. The combination of Pd(OAc)2 with XantPhos proved to be the best for these conversions in the presence of KOt-Bu, in 1,4-dioxane as a solvent, at 90-100 °C. The 8-bromobenzo[f]quinazolin-1(2H)-one 15 was synthesized via condensation of the ethyl or tert-butyl 2-amino-8-bromonaphthalene-1-carboxylate 6, 10 with formamide, followed by reaction with 3,4-dimethoxybenzyl bromide. However, the 6-bromobenzo[h]quinazolin-4(3H)-ones 19a, 19b were prepared from ethyl 4-bromo-1-[(tert-butoxycarbonyl)amino]naphthalene-2-carboxylate (17). Biological screening of the potential cytotoxicity of compounds 16a, 20a, 20c on HT29 and HCT116 cell lines, has shown that compound 20a has a significant anticancer activity.
- Nowak, Monika,Malinowski, Zbigniew,Fornal, Emilia,Jó?wiak, Andrzej,Parfieniuk, Ewa,Gajek, Gabriela,Kontek, Renata
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p. 9463 - 9473
(2015/11/18)
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- N-(1-HYDROXY-3-(PYRROLIDINYL)PROPAN-2-YL)PYRROLIDINE-3-CARBOXAMIDE DERIVATIVES AS GLUCOSYLCERAMIDE SYNTHASE INHIBITORS
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Described herein are compounds of Formula I, methods of making such compounds, pharmaceutical compositions and medicaments containing such compounds, and compounds I for use to treat or prevent diseases or conditions associated with the enzyme glucosylceramide synthase (GCS).
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Paragraph 000705
(2015/05/19)
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- Reduction of hydrazines to amines with aqueous solution of titanium(iii) trichloride
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N-N bond cleavage in hydrazines is widely used in the preparation of amines and thus occupies a significant place in organic synthesis. In this paper, we report a new method for the reductive cleavage of N-N bonds in hydrazines by commercially available and cheap aqueous titanium(iii) trichloride. The reaction proceeds smoothly under a broad pH range from acidic to neutral and basic conditions to afford amines in good yields. This method is compatible with substrates containing functionalities such as C-C double bonds, benzyl-nitrogen bonds, benzyloxy and acyl groups. The Royal Society of Chemistry 2011.
- Zhang, Yan,Tang, Qiang,Luo, Meiming
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supporting information; experimental part
p. 4977 - 4982
(2011/08/05)
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- NOVEL INHIBITORS OF HEPATITIS C VIRUS REPLICATION
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The embodiments provide compounds of the general Formulae I, II, III, IV, or V as well as compositions, including pharmaceutical compositions, comprising a subject compound. The embodiments further provide treatment methods, including methods of treating a hepatitis C virus infection and methods of treating liver fibrosis, the methods generally involving administering to an individual in need thereof an effective amount of a subject compound or composition.
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Page/Page column 264
(2011/07/06)
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- Development of luciferin analogues bearing an amino group and their application as BRET donors
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We systematically synthesized bioluminogenic substrates bearing an amino group on benzothiazole, quinoline, naphthalene, and coumarin scaffolds. They emit bioluminescence in various colors: red, orange, yellow, and green. An amino-substituted cou-marylluciferin derivative, coumarylami-noluciferin (CAL), showed the shortest bioluminescence wavelength among substrates reported so far. Further, the fluorescence of CAL did not exhibit solvatochromism, which suggests that its bioluminescence is not susceptible to environmental factors. We applied CAL as an energy-donor substrate for a bioluminescence resonance energy transfer (BRET) system with click beetle red luciferase (CBRluc), a mutant of firefly luciferase, as the energy-donor enzyme and yellow fluorescent protein (YFP) as the energy-acceptor fluorophore, and obtained a clearly bimodal bioluminescence spectrum. Stable bioluminescence that is not influenced by environmental factors is highly desirable for reliable measurements in biological assays.
- Takakura, Hideo,Sasakura, Kiyoshi,Ueno, Tasuku,Urano, Yasuteru,Terai, Takuya,Hanaoka, Kenjiro,Tsuboi, Takashi,Nagano, Tetsuo
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experimental part
p. 2053 - 2061
(2011/04/23)
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- ANT1VIRAL COMPOUNDS AND USES THEREOF
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This invention relates to: (a) compounds and salts thereof that, inter alia, inhibit HCV; (b) intermediates useful for the preparation of such compounds and salts; (c) compositions comprising such compounds and salts; (d) methods for preparing such intermediates, compounds, salts, and compositions; (e) methods of use of such compounds, salts, and compositions; and (f) kits comprising such compounds, salts, and compositions.
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Page/Page column 74
(2010/11/05)
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- URACIL OR THYMINE DERIVATIVE FOR TREATING HEPATITIS C
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Present application relates to the compounds of formula I useful to treat hepatitis C (HCV) infections. In the structure of the disclosed compounds is the uracil or thymine derivative linked via a phenylene into either fused 2-ring cyclic system (R6) or alternatively via additional two-atom linker (L) to a 5-6 membered monocycle (R6). Application further discloses polymorphs and pseudopolymorphs of two specific compounds: N-(6(3-t-butyl-5-(2>4-dioxo-3,4-dihydropyrimidin-1 (2H)- y!)2-methoxy-phenyl)naphthalen-2-yl)methanesulfonamide and (E)-N-(4(3-t- butyl-5-(2,4-dioxo-3)4-dihydropyrimidin-1 (2H)-yl)2-methoxy-styryl- phenyl)methanesulfonamide.
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Page/Page column 175
(2009/04/25)
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- ANTI-INFECTIVE PYRIMIDINES AND USES THEREOF
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This invention relates to: (a) compounds and salts thereof that, inter alia, inhibit HCV; (b) intermediates useful for the preparation of such compounds and salts; (c) compositions comprising such compounds and salts; (d) methods for preparing such intermediates, compounds, salts, and compositions; (e) methods of use of such compounds, salts, and compositions; and (f) kits comprising such compounds, salts, and compositions.
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Page/Page column 104
(2009/04/25)
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- PHEN-NAPHTHALENE AND PHEN-QUINOLINE DERIVATIVES AND THEIR USE FOR BINDING AND IMAGING AMYLOID PLAQUES
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This invention relates to methods of imaging amyloid deposits, radiolabeled compounds, and methods of making radiolabeled compounds useful in imaging amyloid deposits. This invention also relates to compounds and methods of making compounds for inhibiting the aggregation of amyloid proteins to form amyloid deposits and methods of delivering therapeutic agents to amyloid deposits.
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Page/Page column 53
(2008/12/04)
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- SMALL-MOLECULE INHIBITORS OF THE ANDROGEN RECEPTOR
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The present invention provides a method of inhibiting an androgen receptor by administering a compound of Formula I: or a compound of Formula II: wherein R1, R2, R3 and R8 are each independently hydrogen or C1-6 alkyl. R4 is absent or is hydrogen, C1-6 alkyl or C1-6 alkyl-OH. R5 is hydrogen, C1-6 alkyl or —NR6R7. R6 and R7 are each independently hydrogen or C1-6 alkyl, or are combined with the nitrogen to which they are attached to form a heterocycloalkyl having from 5 to 7 ring members. L is a linker of C1-6 alkylene, C2-6 alkenylene, C2-6 alkynylene or C3-6 cycloalkylene. The compounds of Formula I include the salts, hydrates and prodrugs thereof. Each R9 is H, C1-6 alkyl, —OH or —O—C1-6 alkyl. The compounds of Formulas I and II include the salts, hydrates and prodrugs thereof. By administering the compound of Formula I or II, the method inhibits the androgen receptor.
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Page/Page column 11
(2009/01/20)
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- Structure-activity studies on splitomicin derivatives as sirtuin inhibitors and computational prediction of binding mode
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NAD+-dependent histone deacetylases (sirtuins) are enzymes that cleave acetyl groups from lysines in histones and other proteins. Potent selective sirtuin inhibitors are interesting tools for the investigation of the biological functions of those enzymes and may be future drugs for the treatment of cancer. Splitomicin was among the first two inhibitors that were discovered for yeast sirtuins but showed rather weak inhibition on human enzymes. We present detailed structure-activity relationships on splitomicin derivatives and their inhibition of recombinant Sirt2. To rationalize our experimental results, ligand docking followed by molecular mechanics Poisson-Boltzmann/surface area (MM-PBSA) calculations were carried out. These analyses suggested a molecular basis for the interaction of the beta-phenylsplitomicins with human Sirt2. Protein-based virtual screening resulted in the identification of a novel Sirt2 inhibitor chemotype. Selected inhibitors showed antiproliferative properties and tubulin hyperacetylation in MCF7 breast cancer cells and are promising candidates for further optimization as potential anticancer drugs.
- Neugebauer, Robert C.,Uchiechowska, Urszula,Meier, Rene,Hruby, Henning,Valkov, Vassil,Verdin, Eric,Sippl, Wolfgang,Jung, Manfred
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p. 1203 - 1213
(2008/12/20)
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- Inhibitors of factor Xa
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Novel compounds, their salts and compositions related thereto having activity against mammalian factor Xa are disclosed. The compounds are useful in vitro or in vivo for preventing or treating coagulation disorders.
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- Design, synthesis and biological activity of novel non-amidine factor Xa inhibitors. Part 1: P1 structure-activity relationships of the substituted 1-(2-Naphthyl)-1H-pyrazole-5-carboxylamides
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Based on DuPont Pharmaceuticals' monobenzamidine lead structure SN429, we have designed the biphenyl 1-(2-naphthyl)-1H-pyrazole-5-carboxylamides as a novel series of non-basic factor Xa inhibitors. We have discovered that the displacement of the benzamidine moiety with substituted 2-naphthyl structures not only results in highly potent factor Xa inhibitors, but also significantly increases their enzyme specificity and oral bioavailability.
- Jia, Zhaozhong J.,Wu, Yanhong,Huang, Wenrong,Goldman, Erick,Zhang, Penglie,Woolfrey, John,Wong, Paul,Huang, Brian,Sinha, Uma,Park, Gary,Reed, Andrea,Scarborough, Robert M.,Zhu, Bing-Yan
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p. 1651 - 1655
(2007/10/03)
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- Inhibitors of factor Xa
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Novel compounds, their salts and compositions related thereto having activity against mammalian factor Xa are disclosed. The compounds are useful in vitro or in vivo for preventing or treating coagulation disorders.
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- Synthesis and antinociceptive activity of pyrrolidinylnaphthalenes
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In this paper the synthesis of the racemates (2R,3S/2S,3R)-1,2-dimethyl-3-[2-(6-substituted naphthyl)]-3-hydroxypyrrolidine 1b-d [(2R,3S/2S,3R)-1b-d] are reported. Compounds 1b-d were prepared by reaction of the racemic 1,2-dimethyl-3-pyrrolidone 2 with the lithiation product obtained from 2-bromo-6-substituted naphthalene 3b-d. Pharmacological properties of (2R,3S/2S,3R)-1a-d are also described. Analgesic activity was investigated by the hot plate test and binding affinities towards μ, δ and κ opioid receptors were evaluated. A preliminary evaluation of the in vivo side-effects was also accomplished using the rota-rod test. Interesting antinociceptive activity was shown by all compounds and in particular by 1d, which is the most active compound, since it is six-fold more potent than morphine and has lower side effects on the locomotory activity. Copyright (C) 2000 Elsevier Science Ltd.
- Collina, Simona,Azzolina, Ornella,Vercesi, Dina,Sbacchi, Massimo,Scheideler, Mark Albert,Barbieri, Annalisa,Lanza, Enrica,Ghislandi, Victor
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p. 1925 - 1930
(2007/10/03)
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- Fluorescence of Amphiphilic Hemicyanine Dyes without Free Double Bonds
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Amphiphilic hemicyanine dyes were obtained by coupling unpolar derivatives of aniline and naphthylamine, respectively, to polar derivatives of pyridinium and isoquinolinium, respectively.These dyes have no free double bond that is prone to photoisomerization.They are effective voltage-sensitive probes in biomembranes.The dyes were characterized by their spectra of absorption and by the spectra, the quantum yields, and the lifetimes of fluorescence. (i) An enhanced polarity of solvents shifts the absorption to the blue and the fluorescence to the red.The solvatochromism is described by an enhancement of the Stokes shift at an invariant 00 energy. (ii) An enhanced polarity lowers the quantum yield of fluorescence by orders of magnitude.The effect is described by an enhancement of nonradiative deactivation at an invariant radiative decay.The enhancements of the Stokes shift and of the nonradiative decay are assigned to two types of intramolecular charge-transfer that couple to polar solvents.The first one is induced by electronic excitation.The second one is induced by intramolecular twist in the excited state.The properties of the dyes in amphiphilic assemblies are discussed in terms of their properties in bulk solvents.
- Ephardt, Heinz,Fromherz, Peter
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p. 4540 - 4547
(2007/10/02)
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