- Intermolecular hydrogen bonding controlled stereoselective photocycloaddition of vinyl ethers to 1-cyanonaphthalenes
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With the aim of developing photoreactions that use intermolecular hydrogen bonding interactions to control the efficiency and stereochemistry, the 1,2-[2 + 2] photocycloaddition reactions of 1-cyanonaphthalene derivatives with vinyl ethers possessing hydroxy groups were examined. The photoreaction of 1-cyano-4-(hydroxymethyl)naphthalene (1a) with 2-hydroxyethyl vinyl ether (2a) at room temperature was found to produce cycloadducts, endo-3aa and exo-3aa, in a non-stereoselective manner (56?:?44). However, this photoreaction at ?40 °C displays a high endo-selectivity (81?:?19). In the reaction of 1a with ethyl vinyl ether (2b), high endo selectivity was observed both at room temperature and at ?40 °C. The endo selectivity in the [2 + 2] photocycloaddition process is attributed to the intermolecular hydrogen bonding interactions between the reacting partners in the ground and excited states. Evidence to support this conclusion comes from the results of VT NMR and fluorescence quenching experiments, as well as the photoreactions of deuterated substrates.
- Maeda, Hajime,Takenaka, Hiroki,Mizuno, Kazuhiko
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- Benzimidazole or azabenzimidazole -6 - carboxylic acid compound and application thereof
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The invention discloses benzimidazole or azabenzimidazole -6 - carboxylic acid compound and application thereof, wherein the benzimidazole or azabenzimidazole -6 - carboxylic acid compound has the structure shown in the formula (I). The benzimidazole or a
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Paragraph 0339-0341; 0343
(2021/10/11)
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- Systematic structure-activity relationship (SAR) exploration of diarylmethane backbone and discovery of a highly potent novel uric acid transporter 1 (URAT1) inhibitor
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In order to systematically explore and better understand the structure-activity relationship (SAR) of a diarylmethane backbone in the design of potent uric acid transporter 1 (URAT1) inhibitors, 33 compounds (1a-1x and 1ha-1hi) were designed and synthesized, and their in vitro URAT1 inhibitory activities (IC50) were determined. The three-round systematic SAR exploration led to the discovery of a highly potent novel URAT1 inhibitor, 1h, which was 200-and 8-fold more potent than parent lesinurad and benzbromarone, respectively (IC50 = 0.035 μM against human URAT1 for 1h vs. 7.18 μM and 0.28 μM for lesinurad and benzbromarone, respectively). Compound 1h is the most potent URAT1 inhibitor discovered in our laboratories so far and also comparable to the most potent ones currently under development in clinical trials. The present study demonstrates that the diarylmethane backbone represents a very promising molecular scaffold for the design of potent URAT1 inhibitors.
- Cai, Wenqing,Wu, Jingwei,Liu, Wei,Xie, Yafei,Liu, Yuqiang,Zhang, Shuo,Xu, Weiren,Tang, Lida,Wang, Jianwu,Zhao, Guilong
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- Preparation of polycyclic compounds by intramolecular photospirocyclization and photocycloaddition reactions of 4-alkenyl-1-cyanonaphthalene derivatives
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Photoreactions of 4-pentenyl-1-cyanonaphthalenes yield spirocyclic products along with [4?+?2] cycloadducts. Photoreactions of 5-phenyl derivatives produce a product having tricyclo[6.3.0.01,4]undecadiene skeleton. Formation of angular triquinanes takes place in photoreactions of cycloalkene-linked cyanonaphthalenes. The observation demonstrates that π–π arene ring interactions, steric hindrance, and suitable locations of reaction sites in syn and anti singlet exciplexes govern the modes followed in intramolecular photoreactions of 4-alkenyl-1-cyanonaphthalenes.
- Maeda, Hajime,Wada, Hidenori,Mukae, Hirofumi,Mizuno, Kazuhiko
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- SUBSTITUTED 4-ARYL-1,4-DIHYDRO-1,6-NAPHTHYRIDINAMIDES AND USE THEREOF
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1,6-Naphthyridine or 8-azaquinazoline derivatives (I) are new. 1,6-Naphthyridine or 8-azaquinazoline derivatives of formula (I) are new. D : N or CR 4>; R 4> : H, F, CF 3 or 1-4C alkyl; Ar : 5-R 5>-6-R 6>-2-methyl-4-oxo-4H-1-benzopyran-8-yl; 3-R 6>-4-R 8>-1-naphthyl optionally substituted with 1-3 of R 7>; 7-R 6>-8-R 8>-5-quinolinyl optionally substituted with 1-2 of R 7>; or 2-R 9>-3-R 10>-4-R 8>-5-R 6>-phenyl; R 5> : H, F, Cl, CN, NO 2, CF 3 or 1-4C alkyl; R 6> : H or F; R 7> : halo, 1-4C alkyl, CF 3, 1-4C alkoxy or OCF 3; R 8> : CN or NO 2; R 9> : H or halo; optionally fluorinated 1-4C alkyl, 1-4C alkoxy, 1-4C alkylthio of di(1-4C alkyl)amino; or phenyl optionally substituted with halo, 1-4C alkyl or CF 3; R 10> : H, halo or 1-4C alkyl; R 1> : optionally fluorinated 1-4C alkyl; R 2> : 1-6C alkyl optionally substituted with 3-7C cycloalkyl or F; or SO 2R 11>; R 11> : 1-6C alkyl, CF 3 or 3-7C cycloalkyl; or phenyl or heteroaryl optionally substituted with 1-2 of halo, CN, 1-4C alkyl, CF 3, 1-4C alkoxy and/or OCF 3; R 3> : H, F, CF 3 or 1-4C alkyl. An independent claim is also included for a process for preparing (I). [Image] ACTIVITY : Hypotensive; Cardiant; Hepatotropic; Nephrotropic; Cerebroprotective. MECHANISM OF ACTION : Mineralocorticoid receptor (MR) antagonist. 4-(4-cyano-2-methoxyphenyl)-5-ethoxy-2-methyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide had an IC 50 of 35 nM when tested on cells expressing a GAL4-MR chimera.
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Paragraph 0369-0372
(2016/10/17)
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- Intramolecular Photocycloaddition Reactions of Arylcyclopropane Tethered 1-Cyanonaphthalenes
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Intramolecular photocycloaddition reactions of 1-cyanonaphthalenes bearing an arylcyclopropane containing side chain were investigated. Photoreactions of members of this family in which the arylcyclopropane moiety is bonded at the 2-position of the 1-cyanonaphthalene ring produce head-to-head and head-to-tail 1,2-[3+2] photocycloadducts. On the other hand, substances in this family containing an arylcyclopropane side chain linked to the 4-position of the cyanoarene ring undergo photoreactions to form [4+3] photocycloadducts along with novel nine-membered ring products, which are produced by photochemically induced 10 conrotatory ring opening of the initially formed intramolecular [3+2] cycloadducts. The results of solvent effects and fluorescence investigations along with those focusing on corresponding intermolecular photoreactions demonstrate that the photocycloadducts are formed predominantly through an intramolecular exciplex mechanism and that a photoinduced intramolecular electron transfer pathway via zwitterionic biradicals might be partly responsible for the process when CH3CN is the solvent.
- Maeda, Hajime,Matsuda, Shoji,Mizuno, Kazuhiko
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p. 8544 - 8551
(2016/09/28)
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- Pesticidal compositions and processes related thereto
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This document discloses molecules having the following formula (“Formula One”): and processes associated therewith.
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Page/Page column 112
(2016/01/09)
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- PESTICIDAL COMPOSITIONS AND PROCESSES RELATED THERETO
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This document discloses molecules having the following formula ("Formula One"): and processes associated therewith.
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Page/Page column 110; 111
(2014/07/08)
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- PESTICIDAL COMPOSITIONS AND PROCESSES RELATED THERETO
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This document discloses molecules having the following formula (“Formula One”): and processes associated therewith.
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Paragraph 0549-0550
(2014/06/25)
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- PESTICIDAL COMPOSITIONS AND PROCESSES RELATED THERETO
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This document discloses molecules having the following formula (“Formula One”): and processes associated therewith.
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Paragraph 0714; 0715
(2014/06/25)
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- PESTICIDAL COMPOSITIONS AND PROCESSES RELATED THERETO
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This document discloses molecules having the following formula ("Formula One") and processes associated therewith.
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Page/Page column 111
(2014/07/08)
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- PESTICIDAL COMPOSITIONS AND PROCESSES RELATED THERETO
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This document discloses molecules having the following formula (“Formula One”): and processes associated therewith.
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Page/Page column
(2014/06/25)
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- PESTICIDAL COMPOSITIONS AND PROCESSES RELATED THERETO
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This document discloses molecules having the following formula (“Formula One”): and processes associated therewith.
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Page/Page column 60
(2013/02/28)
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- SUBSTITUTED-4-ARYL-1,4-DIHYDRO-1,6-NAPHTHYRIDINAMIDES AND USE THEREOF
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The present application relates to novel substituted 4-aryl-1,4-dihydro-1,6-naphthyridine-3-carboxamides, a process for their preparation, their use for the treatment and/or prophylaxis of diseases, and their use for the manufacture of medicaments for the treatment and/or prophylaxis of diseases, especially cardiovascular disorders.
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- SUBSTITUTED 4-ARYL-1,4-DIHYDRO-1,6-NAPHTHYRIDINES AND USE THEREOF
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The present application relates to novel substituted 4-aryl-1,4-dihydro-1,6-naphthyridines, a process for their preparation, their use for the treatment and/or prophylaxis of diseases, and their use for the manufacture of medicaments for the treatment and/or prophylaxis of diseases, especially cardiovascular disorders.
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Page/Page column 8-9; 26
(2010/12/29)
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- Hierarchical self-assembly of heteronuclear co-ordination networks
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Two ligands L1 and L2 have been prepared which contain a chelating pyrazolyl-pyridine group with a pendant aromatic nitrile (in L1, a benzonitrile; in L2, a naphthonitrile). These ligands react with Ag(i) salts to give a range of infinite coordination networks or dimeric 'boxes' in which the pyrazolyl-pyridine chelates and the aromatic nitrile groups both participate in coordination to Ag(i) ions. In contrast, L1 and L2 form simple mononuclear tris-chelates [ML 3]2+ with first-row transition metal dications (M = Co, Ni, Zn) in which the aromatic nitrile groups are pendant such that the complexes can be used as 'complex ligands'. The crystal structures of [M(L 2)3](BF4)2 are based on solely the mer tris-chelate geometry although in solution 1H NMR spectroscopy reveals a mixture of both fac and mer isomers of the tris-chelates. Reaction of these with Ag(i) ions allows the interaction of the pendant nitrile groups with Ag(i) ions to generate coordination networks based on [ML3] 2+ cations being crosslinked by Ag(i) ions. In these networks the [ML3]2+ cations have solely the fac geometry and lie on threefold rotation axes with all three pendant nitrile groups coordinated to Ag(i) ions which are three-coordinate. {[AgM(L2)3][BF 4]3}∞ (M = Co, Ni) consist of two interpenetrated (10,3)a nets which have opposite chirality at the [M(L 2)3]2+ centres but are not strictly enantiomorphic as the two nets are not crystallographically equivalent. {[AgNi(L1)3](BF4)3} ∞ in contrast contains two-dimensional sheets which have a (6,3) net structure of hexagonal rings of alternative Ni(ii) and Ag(i) centres; although not interpenetrating, two such adjacent (and enantiomorphic) sheets interact with each other via numerous CH...π interactions between aromatic ligands. Formation of these structures shows that the differential reactivity of the two binding sites in L1 and L2 (pyrazolyl-pyridine, and nitrile) can be used to generate mixed-metal coordination networks in a hierarchical, stepwise manner.
- Fenton, Hazel,Tidmarsh, Ian S.,Ward, Michael D.
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p. 3805 - 3815
(2010/06/17)
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- Phenyl-1,2,4-Oxadiazolone Derivatives, Processes For Their Preparation and Methods For Their Use as Pharmaceuticals
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The inventive compounds of the present invention are comprised of phenyl and pyridinyl-1,2,4-oxadiazolone derivatives and their physiologically acceptable salts and functional derivatives that are shown to provide peroxisome proliferator activator recepto
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Page/Page column 69
(2008/12/04)
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- Naphthonitrile-Alkene Exciplexes. Comparison of Bimolecular and Bichromophoric Cases: Effects of Linking on Fluorescence and Photochemistry
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The fluorescence quenching and photochemistry of 2-methyl-, 4-methyl-, and 6-methyl-1-naphthonitrile with tetramethylethylene have been studied in nonpolar solvents.Stern-Volmer constants (benzene solvent) are 10.1, 15.7, and 7.2 M-1, respectively, showing that quenching is insensitive to the position of the methyl group.Exciplex emission was observed in each case, and exciplex lifetimes were measured by single photon counting techniques.The methylnaphthonitriles react with tetramethylethylene to give 1-cyano-7,7,8,8-tetramethyl-2,3-benzobicyclo-2,4-octadiene derivatives, and limiting quantum yields were measured.In the case of 4-methyl-1-naphthonitrile, quenching with biacetyl showed that the exciplex is an intermediate in the cycloaddition reaction and no triplets are formed in the exciplex decay.Rates of exciplex collapse to cyclobutane products were derived.The bichromophoric molecules 1, 2, and 3, in which the chromophores are linked by a three-atom chain, were synthesized.All three show strong quenching of the monomer (naphthonitrile) fluorescence, and weak exciplex emission.Compounds 1, 2, and 3 also react on irradiation, giving internal cycloaddition products.The structures of the latter were determined, and the structure work is described.Comparison of quantum yields for internal cycloaddition with limiting quantum yields for the bimolecular cases shows that the three-atom chain greatly facilitates collapse of the exciplexes to products in these systems.Exciplex formation and decay are discussed in terms of current theory.The structure of one photoproduct, 7-cyano-5,6,6-trimethyl-8,9-benzo-3-oxatricyclo1,5>-8,10-undecadiene (10), was determined by X-ray diffraction, and the structure is described.
- McCullough, John J.,MacInnis, W. Keith,Lock, Colin J. L.,Faggiani, Rommulo
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p. 4644 - 4658
(2007/10/02)
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- Preparation of a series of substituted fluoromethylnaphthalenes
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A series of 22 3- and 4-substituted 1-fluoromethylnaphthalenes have been synthesized.Details of practical procedures for the preparation of all intermediates are described, and physical properties for all of the substituted naphthalenes synthesized, and spectral parameters for 51 previously unknown compounds, are given.
- Dixon, Elisabeth A.,Fischer, Alfred,Robinson, Frank P.
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p. 2629 - 2641
(2007/10/02)
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