- 5,11-Diazadibenzo[hi,qr]tetracene: Synthesis, Properties, and Reactivity toward Nucleophilic Reagents
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5,11-Diazadibenzo[hi,qr]tetracene was synthesized as a new nitrogen-substituted polycyclic heteroaromatic compound by Pd-catalyzed cycloisomerization of an alkyne precursor followed by oxidative cyclization with bis(trifluoroacetoxy)iodobenzene. The substitution of imine-type nitrogen atoms significantly enhanced its electron-accepting character and facilitated the direct nucleophilic addition of arylamines under strongly basic conditions to afford the desired amino-substituted products. The introduction of amino groups induced a remarkable red-shift in their absorption spectra; the tetrasubstituted product exhibited intense near-infrared absorbing property. Furthermore, the π-electronic system, which includes a redox-active 1,4-diazabutadiene moiety, underwent reversible interconversion to its corresponding reduced form upon reduction with NaBH4 and aerobic oxidation.
- Fujimoto, Keisuke,Takimoto, Satoshi,Masuda, Shota,Inuzuka, Toshiyasu,Sanada, Kazutaka,Sakamoto, Masami,Takahashi, Masaki
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Read Online
- INHIBITORS OF KRAS G12C PROTEIN AND USES THEREOF
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Provided are novel compounds useful as inhibitors of the KRAS protein, as well as pharmaceutical compositions comprising these compounds and methods of treatment by administration of these compounds or the pharmaceutical compositions.
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Paragraph 00218; 00219
(2021/12/28)
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- KRAS G12D INHIBITORS
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The present invention relates to compounds that inhibit KRas G12D. In particular, the present invention relates to compounds that inhibit the activity of KRas G12D, pharmaceutical compositions comprising the compounds and methods of use therefor.
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Paragraph 0244
(2021/03/05)
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- COVALENT RAS INHIBITORS AND USES THEREOF
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The disclosure features compounds, or pharmaceutically acceptable salts thereof, alone and in combination with other therapeutic agents, pharmaceutical compositions, and protein conjugates thereof, capable of modulating biological processes including Ras, and their uses in the treatment of cancers.
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Page/Page column 260
(2021/06/04)
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- Multi-layer 3D chirality: new synthesis, AIE and computational studies
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New synthesis of multi-layer 3D chiral molecules has been developed under novel conditions to give better outcomes. The aggregation-induced emission (AIE), UV irradiation/excitation, charge transfer (CT) and local excited (LE) ππ* transitions have been investigated on a representative individual enantiomer of pseudo C2 asymmetry which was made possibly by differentiating moieties on phosphorous on N-phosphonyl ring of chiral sandwich framework. Meanwhile, a new tandem C-N/C-C coupling reaction was unexpectedly rendered providing a novel access to special benzo[a]carbazoles.
- Liu, Yangxue,Wu, Guanzhao,Yang, Zhen,Rouh, Hossein,Katakam, Nandakumar,Ahmed, Sultan,Unruh, Daniel,Cui, Zhonghua,Lischka, Hans,Li, Guigen
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p. 692 - 698
(2020/04/15)
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- COMPOUND, ACTIVE MATERIAL FOR STORAGE BATTERY, n-TYPE SEMICONDUCTOR MATERIAL, HYDROGEN STORAGE MATERIAL, AND METHOD FOR PRODUCING COMPOUND
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PROBLEM TO BE SOLVED: To provide a new compound, an active material for a storage battery, an n-type semiconductor material, a hydrogen storage material, and a method for producing the new compound. SOLUTION: The compound is represented by the following Formula 1. In the following Formula 1, a ring structure A1 includes a ring structure that contains a nitrogen atom and has m carbon atoms, in which carbons in the ring structure having m carbon atoms, which do not constitute a ring structure A2, are not bonded to a hydrogen atom and constitute an aromatic ring; a ring structure A2 includes a ring structure that contains a nitrogen atom and has n carbon atoms, in which carbons in the ring structure having n carbon atoms, which do not constitute the ring structure A1, are not bonded to a hydrogen atom and constitute an aromatic ring; m is an integer of 4 to 7; and n is an integer of 5 to 7. There are also provided the active material for the storage battery, the n-type semiconductor material, the hydrogen storage material, and the method for producing the compound. SELECTED DRAWING: None COPYRIGHT: (C)2020,JPOandINPIT
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Paragraph 0054
(2020/11/13)
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- Structural modifications of nile red carbon monoxide fluorescent probe: Sensing mechanism and applications
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Carbon monoxide (CO) is a cell-signaling molecule (gasotransmitter) produced endogenously by oxidative catabolism of heme, and the understanding of its spatial and temporal sensing at the cellular level is still an open challenge. Synthesis, optical properties, and study of the sensing mechanism of Nile red Pd-based CO chemosensors, structurally modified by core and bridge substituents, in methanol and aqueous solutions are reported in this work. The sensing fluorescence "off-on" response of palladacycle-based sensors possessing low-background fluorescence arises from their reaction with CO to release the corresponding highly fluorescent Nile red derivatives in the final step. Our mechanistic study showed that electron-withdrawing and electron-donating core substituents affect the rate-determining step of the reaction. More importantly, the substituents were found to have a substantial effect on the Nile red sensor fluorescence quantum yields, hereby defining the sensing detection limit. The highest overall fluorescence and sensing rate enhancements were found for a 2-hydroxy palladacycle derivative, which was used in subsequent biological studies on mouse hepatoma cells as it easily crosses the cell membrane and qualitatively traces the localization of CO within the intracellular compartment with the linear quantitative response to increasing CO concentrations.
- Klán, Petr,Madea, Dominik,Martínek, Marek,Muchová, Lucie,Váňa, Ji?í,Vítek, Libor
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p. 3473 - 3489
(2020/03/25)
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- Close Amide NH···F Hydrogen Bonding Interactions in 1,8-Disubstituted Naphthalenes
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In this note, we present a series of N-(8-fluoronaphthalen-1-yl)benzamide derivatives designed to maximize amide-NH···F hydrogen bond interactions therein. A combination of IR and NMR spectroscopy indicates a linear correlation between the high energy shi
- Kazim, Muhammad,Siegler, Maxime A.,Lectka, Thomas
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p. 6195 - 6200
(2020/05/22)
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- CHIRAL ORGANIC SANDWICH AND MULTI-LAYER CHIRALITY OF MOLECULES AND ACHIRAL DERIVATIVES
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The present invention includes a multi-layer 3D material, a method of making, and a catalyst comprising: a first, a second, and a third layer, wherein each of the layers are arranged in a nearly parallel fashion with chirality along a center plane.
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Paragraph 0035
(2020/07/08)
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- KRAS G12C INHIBITORS
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The present invention relates to compounds that inhibit KRas G12C. In particular, the present invention relates to compounds that irreversibly inhibit the activity of KRas G12C, pharmaceutical compositions comprising the compounds and methods of use therefor.
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Paragraph 0306
(2020/07/25)
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- KRAS G12C INHIBITORS
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The present invention relates to compounds that, inhibit KRas G12C, In particular, the present invention relates to compounds that irreversibly inhibit the activity of KRas G12C, pharmaceutical compositions comprising the compounds and methods of use therefor.
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Paragraph 0309-0310
(2020/03/23)
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- Ethylene Polymerization with Ni(II) Diimine Complexes Generated from 8-Halo-1-naphthylamines: The Role of Equilibrating Syn/ Anti Diastereomers in Determining Polymer Properties
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A series of 8-halonapthalen-1-amines (6a-d, X = F, Cl, Br, I) were prepared and converted to the α-diimines of 2,3-butanedione (7a-d). The nickel dibromide and zinc dibromide complexes of these diimines (3a-d and 8a-d, respectively) were obtained in good yields from standard precursors. NMR spectroscopic analysis of the zinc diimine complexes show the existence of syn and anti diastereomers with syn/anti ratios of ca. 2:1 (F), 2:1 (Cl), 1:1.5 (Br), and ca. 1:22 (I). Variable temperature NMR spectroscopy was used to calculate barriers to interconversion of these diastereomers which fall in the range 17-18.5 kcal/mol. Activation of nickel dibromide complexes 3a-d with modified methyl alumoxane (MMAO) yields cationic diimine complexes in which the 8-halo substituents lie over the axial coordination sites. Ethylene polymerization using these activated complexes is reported. The anti diastereomer of the diiodo catalyst (10d) in which both axial sites are blocked yields high molecular weight PE (ca. 106 g/mol) as the major fraction with a high turnover frequency at 40 °C. The minor syn diastereomer of 10d in which only one axial site is blocked produces low molecular weight PE as a minor fraction. PE formed from the dichloro catalyst 10b also exhibits a bimodal polymer distribution, but the high molecular weight fraction from the anti diastereomer is minor, while the syn diastereomer produces low molecular weight PE. The dibromo complex (10c) is unique in that interchange of diastereomers is on a time scale such that the PE produced shows a very broad molecular weight distribution (MWD ca. 14), spanning the range from the low to high molecular weight regimes. Catalyst 10a, bearing the small fluoro substituents, yields very low molecular weight PE (ca. 600 g/mol).
- Wang, Bin,Daugulis, Olafs,Brookhart, Maurice
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p. 4658 - 4668
(2019/12/24)
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- KRAS G12C INHIBITORS
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The present invention relates to compounds that inhibit KRas G12C. In particular, the present invention relates to compounds that irreversibly inhibit the activity of KRas G12C, pharmaceutical compositions comprising the compounds and methods of use therefor.
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Paragraph 0487-0488
(2019/05/24)
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- Permethylated salts and radicals derived from azo peri-naphthalenes
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By careful choice of reaction conditions 1-methylnaphtho[1,8-de]-1,2,3- triazine and 1,3-dimethylnaphtho[1,8-de]-1,2,3-triazinium triflate are readily prepared by the alkylation of 1Hnaphtho[1,8-de]-1,2,3-triazine. The electronic spectra for these bathochromically shifted dyes are reported for a range of solvents as are their vibrational spectra and theoretical structures from density functional theory, B3LYP/6-311++G**. The 15N substitution into the middle nitrogen atom allows for the identification of strong azine bands in the IR and Raman spectra as well as in the 15N NMR spectrum. X-ray crystallography is used to characterize the solid-state structures of two of these new triazine derivatives and these structures are used to benchmark the theoretical and spectroscopic discussions. The corresponding 1,3-dimethyltriazinium radical is prepared and characterized by cyclic voltammetry, spectroelectrochemistry, and EPR spectroscopy. Unlike the related transient 1,2,4-triazene radicals, the 1,3-dimethyl-1,2,3-naphthotriazyl radical is markedly more stable.
- Bohle, D. Scott,Chua, Zhijie,Johnstone, Timothy,Moiseev, Andrey G.,Perepichka, Inna,Rosadiuk, Kristopher A.
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p. 387 - 395
(2014/01/17)
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- NH+ - F hydrogen bonding in a fluorinated "Proton Sponge" derivative: Integration of solution, solid-state, gas-phase, and computational studies
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We report detailed studies on the characterization of an intramolecular NH - F hydrogen bond formed within a fluorinated "proton sponge" derivative. An ammonium ion, generated from 8-fluoro-N,N-dimethylnaphthalen-1- amine, serves as a charged hydrogen bond donor to a covalently bound fluorine appropriately positioned on the naphthalene skeleton. Potentiometric titrations of various N,N-dimethylnaphthalen-1-amines demonstrate a significant increase in basicity when hydrogen bonding is possible. X-ray crystallography reveals that NH - F hydrogen bonding in protonated 8-fluoro-N,N-di-methylnaphthalen-1-amine is heavily influenced by ion pairing in the solid state; bifurcated and trifurcated hydrogen bonds are formed depending on the counterion utilized. Compelling evidence of hydrogen bonding in the 8-fluoro-N,N-dimethylnaphthyl-1- ammonium cation is provided by gas-phase cryogenic vibrational photodissociation spectroscopy. Solution-phase infrared spectroscopy provides complementary results, and the frequencies of the N - H stretching mode in both phases are in excellent agreement with the computed vibrational spectra. NMR analysis of protonated 8-fluoro-N,N-dimethylnaphthalen-1-amine demonstrates significant H - F coupling between the N - H hydrogen and fluorine that cannot be attributed to long-range, through-bond interactions; the couplings correlate favorably with calculated values. The results obtained from these experiments are congruent with the formation of an NH - F hydrogen bond upon protonation of 8-fluoro-N,N-dimethylnaphthalen-1-amine.
- Scerba, Michael T.,Leavitt, Christopher M.,Diener, Matthew E.,De Blase, Andrew F.,Guasco, Timothy L.,Siegler, Maxime A.,Bair, Nathaniel,Johnson, Mark A.,Lectka, Thomas
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scheme or table
p. 7975 - 7984
(2011/12/01)
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- Synthesis and crystallography of 8-halonaphthalene-1-carbonitriles and naphthalene-1,8-dicarbonitrile
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A convenient and high-yielding three-step synthesis of 8-halonaphthalene-1- carbonitriles has been achieved by ring opening of 1H-naphtho[1,8-de][1,2,3] triazine with the corresponding halides as the key step. Naphthalene-1,8- dicarbonitrile also has been synthesised from 8-bromonaphthalene-1-carbonitrile via palladium-catalysed cyanation of the aryl bromide. The crystal structures of 8-chloronaphthalene-1-carbonitrile, the A polymorph of the bromo analogue, and naphthalene-1,8-dicarbonitrile are isomorphous with orthorhombic symmetry. The B polymorph of the bromo compound and the iodo analogue are also isomorphous, but with monoclinic symmetry. In all of the halo carbonitriles, the molecules are disordered with respect to the location of the halogen atoms and the nitrile groups. There are no intermolecular X...NC interactions in any of the solids.
- Noland, Wayland E.,Narina, Venkata Srinivasarao,Britton, Doyle
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scheme or table
p. 694 - 697
(2012/03/11)
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- Planar chiral flavinium salts - Prospective catalysts for enantioselective sulfoxidation reactions
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A novel planar chiral flavinium salt, 3-benzyl-5-ethyl-10-(8- phenylnaphthalen-1-yl)isoalloxazinium perchlorate (2b), which bears a phenyl cap that covers one side of the isoalloxazinium skeleton plane, has been prepared as a potential catalyst for the enantioselective H2O2 oxidation of sulfides. The rate of H2O2 oxidation of sulfides in the presence of racemic 2b is comparable to that of the reaction catalysed by 5-ethyl-3,10-dimethylisoalloxazinium perchlorate, which indicates that the bulky shielding substituent does not influence the catalytic activity of the flavinium unit. The turnover frequency for the oxidation of thioanisole with hydrogen peroxide with 2b is 870 h-1. The enantiomerically pure salts (+)-2b and (-)-2b were prepared from the pure enantiomers (+)-3b and (-)-3b of 3-benzyl-10-(8-phenylnaphthalen-1-yl)isoalloxazine (3b) obtained by HPLC separation of racemic 3b on a chiral stationary phase. The enantiomerically pure salts (+)-2b and (-)-2b catalyse the H2O2 oxidation of para-substituted thioanisoles with enantiomeric excesses of 34-44%. The highest enantioselectivity (54% ee) was observed in the oxidation of methyl naphthyl sulfide.
- Jurok, Radek,Cibulka, Radek,Dvorakova, Hana,Hampl, Frantisek,Hodacova, Jana
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experimental part
p. 5217 - 5224
(2010/11/02)
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- METHOD OF MAKING 8-FLUORO-NAPHTHALEN-1-YLAMINE AND RELATED COMPOUNDS
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A process is described for preparing 8-flouro-napthalen-l-ylamine comprising reacting lH-naphtlio[l,8-de][l,2,3]triazine with hydrogen fluoride or a complex of hydrogen fluoride and an n-donor base. A process is also set forth for using 8-fluoro- naphthalen-1-ylamine produced as described above in the preparation of l-(8-fluoro- napthalen-l-yl)-piperazine, which can be used as an intermediate in the production of 7- { 4- [4-(8-fluoro-napthalen- 1 -yl)-piperazin- 1 -yl] -butoxy } -3 ,4-dihydro- IH- [l,8]naphthyridin-2-one, a D2 partial agonist indicated for possible use in the treatment of schizophrenia.
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Page/Page column 6-7
(2008/06/13)
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- Practical alternative synthesis of 1-(8-Fluoro-naphthalen-1-yl)piperazine
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Convergent synthesis of 8-fluoronaphthalen-1-ylamine (6) was achieved through the reaction of 1H-tauphtho[1,8-de][1,2,3]triazine (15) with HF-pyridine under mild conditions. This new synthesis for the preparation of 6 overcame many scale-up challenges that exist in the methods reported in the literature and provided a practical alternative synthesis of 1-(8-fluoronaphthalen-1-yl) piperazine (1).
- Zhu, Zhijian,Colbry, Norm L.,Lovdahl, Mark,Mennen, Kenneth E.,Acciacca, Alison,Beylin, Vladimir G.,Clark, Jerry D.,Belmont, Daniel T.
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p. 907 - 909
(2012/12/30)
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- Gas-phase thermolysis of 1-acylnaphtho[1,8-de][1,2,3]triazines. Interesting direct routes towards condensed naphtho[1,8-de]heterocyclic ring systems
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FVP pyrolysis of 1-acylnaphtho[1,8-de][1,2,3]triazines at 500°C and 10-2 Torr gave exclusively the corresponding 2-substituted naphtho[1,8-de][1,3]oxazines. The latter was also obtained by static pyrolysis but in lower yield along with the corresponding N-(naphthalen-1-yl)acylamides. The reaction was studied kinetically and mechanistically.
- Al-Awadi, Hanan,Ibrahim, Maher R.,Dib, Hicham H.,Al-Awadi, Nouria A.,Ibrahim, Yehia A.
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p. 10507 - 10513
(2007/10/03)
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- An α-aminomethyl carbanion equivalent via a novel Barbier reaction: (1H-naphtho[ 1,8-de]-1,2,3-triazin-2-yl)methyl anion
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A novel sonication-promoted Barbier reaction putatively generated the titled species from the corresponding naphthotriazinylmethyl chloride and magnesium in THF: its formal addition to a variety of carbonyl compounds in situ occurred in excellent yields. Subsequent catalytic hydrogenolysis of the triazine moiety demasked the amine, thus defining a route to various phenylethylamines (including the alkaloid 'mescaline'), or ethanolamines (in two cases), in excellent overall yields. (C) 2000 Elsevier Science Ltd.
- Chandrasekhar, Sosale,Sridhar, Malayalam
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p. 4685 - 4688
(2007/10/03)
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