- Transition-metal-free, one-pot synthesis of benzoxaboroles from: O -bromobenzaldehydes via visible-light-promoted borylation
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A novel and simple one-pot stepwise method to synthesize benzoxaboroles was demonstrated. This step-by-step synthetic method includes photocatalytic boronization with phenothiazine as a photocatalyst and sequential water-induced reduction in the presence of bis(pinacolato)diboron. A series of o-bromobenzaldehydes were well-tolerated under the standard conditions. In addition, this method has been successfully applied in the synthesis of the anti-tuberculosis candidate drug GSK 3036656 and anti-fungal drug tavaborole. This journal is
- Chen, Jianchao,Hu, Yanjun,Jia, Xingxing,Luo, Jinghan,Sun, Tiemin
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p. 10455 - 10459
(2021/12/17)
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- Inhibiting protein prenylation with benzoxaboroles to target fungal plant pathogens
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Fungal pathogens pose an increasing threat to global food security through devastating effects on staple crops and contamination of food supplies with carcinogenic toxins. Widespread deployment of agricultural fungicides has increased crop yields but is driving increasingly frequent resistance to available agents and creating environmental reservoirs of drug-resistant fungi that can also infect susceptible human populations. To uncover non-cross-resistant modes of antifungal action, we leveraged the unique chemical properties of boron chemistry to synthesize novel 6-thiocarbamate benzoxaboroles with broad spectrum activity against diverse fungal plant pathogens. Through whole genome sequencing of Saccharomyces cerevisiae isolates selected for stable resistance to these compounds, we identified mutations in the protein prenylation-related genes, CDC43 and ERG20. Allele-swapping experiments confirmed that point mutations in CDC43, which encodes an essential catalytic subunit within geranylgeranyl transferase I (GGTase I) complex, were sufficient to confer resistance to the benzoxaboroles. Mutations in ERG20, which encodes an upstream farnesyl pyrophosphate synthase in the geranylgeranylation pathway, also conferred resistance. Consistent with impairment of protein prenylation, the compounds disrupted membrane localization of the classical geranylgeranylation substrate Cdc42. Guided by molecular docking predictions, which favored Cdc43 as the most likely direct target, we overexpressed and purified functional GGTase I complex to demonstrate direct binding of benzoxaboroles to it and concentration-dependent inhibition of its transferase activity. Further development of the boron-containing scaffold described here offers a promising path to the development of GGTase I inhibitors as a mechanistically distinct broad spectrum fungicide class with reduced potential for cross-resistance to antifungals in current use.
- Cowen, Leah E.,Frederick, Brittany H.,Kim, Sang Hu,Liu, C. Tony,Liu, Chunliang,Mcgregor, Cari,Steere, Luke,Whitesell, Luke,Zhang, Yong-Kang,Zhou, Yasheen
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p. 1930 - 1941
(2020/07/14)
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- BORON CONTAINING COMPOUNDS AND THEIR USES
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The present disclosure contemplates novel boron-containing compounds and their uses as active agents that exhibit pesticidal activity such as antimicrobial, insecticidal, arachnicidal, and/or anti parasitic activity. An agrochemical composition containing such a compound and its use in, animal health, agriculture, or horticulture is also contemplated. A method for promoting plant performance and/or controlling, reducing, preventing, ameliorating, or inhibiting microbes, insects, arachnids, and/or parasites on or in an animal, a plant, a plant part, plant propagation material, and/or harvested fruits or vegetables is also contemplated.
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Paragraph 0219-0220; 0343; 0343
(2020/03/29)
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- Synthesis and biological evaluation of arylphosphonium-benzoxaborole conjugates as novel anticancer agents
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Arylphosphonium-benzoxaborole conjugates have been synthesized as potential mitochondria targeting anticancer agents. The synthesized compounds have been tested for their effects on cell viability in various solid tumor cell lines including breast cancer 4T1 and MCF-7, pancreatic cancer MIAPaCa-2 and colorectal adenocarcinoma WiDr. Compound 6c is designated as a lead compound for further studies due to its enhanced effects on cell viability in the above-mentioned cell lines. Seahorse Xfe96 based metabolic assays reveal that the lead candidate 6c inhibits mitochondrial respiration in 4T1 and WiDr cell lines as evidenced by the reduction of mitochondrial ATP production and increase in proton leak. Epiflourescent microscopy experiments also illustrate that 6c causes significant mitochondrial fragmentation in 4T1 and WiDr cells, morphologically consistent with programmed cell death. Our current studies illustrate that arylphosphonium-benzoxaborole conjugates have potential to be further developed as anticancer agents.
- Jonnalagadda, Shirisha,Jonnalagadda, Sravan K.,Jonnalagadda, Subash C.,Kiprof, Paul,Mereddy, Venkatram R.,Ronayne, Conor T.,Wielenberg, Kevin
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- Benzoxaborole-1-alcohol compound and preparation method and application thereof
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The invention belongs to the field of bactericides, and particularly relates to a benzoxaborole-1-alcohol compound and a preparation method and application thereof. The benzoxaborole-1-alcohol compound has good bactericidal activity, can effectively control tomato early blight, wheat scab, rice sheath blight disease, strawberry gray mold, apple blotch, cucumber anthracnose and other crop diseases,can produce excellent antibacterial effects at low concentration, and shows good selectivity. The compound is used as a leucyl-tRNA synthetase inhibitor, the evolution difference of aminoacyl-tRNA synthetase of germs and eukaryotes is utilized, and the compound has very high safety to non-target organisms while killing the germs and can be used as a bactericide in agriculture.
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Paragraph 0078-0079; 0089-0092
(2020/06/24)
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- PROTECTIVE GROUPS AND METHODS FOR PROTECTING BENZOXABOROLES OR OXABOROLES
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The present invention relates in part protective groups that can be used to reversibly protect benzoxaboroles and/or oxaboroles and yield the corresponding protected complexes. The invention further relates to the use of these protective groups to protect benzoxaboroles and/or oxaboroles.
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Page/Page column 50; 51
(2019/10/01)
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- Protection of the Benzoxaborole Moiety: Synthesis and Functionalization of Zwitterionic Benzoxaborole Complexes
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The synthesis and utility of three benzoxaborole protecting groups are reported. These protecting groups improve organic solubility and allow otherwise incompatible reactions (oxidations, substitutions, and mild reductions) to be achieved in the presence of the benzoxaborole moiety. 3-(N,N-Dimethylamino)-1-propanol was determined to be useful in one-step sequences and is readily cleaved upon workup. Two other groups, N-methylsalicylidenimine and 2-[1-(methylimino)ethyl]phenol, are suitable for multistep syntheses. Deprotection with mild aqueous acid allows for chromatography-free isolation of the benzoxaborole in high yields.
- Gamrat, James M.,Mancini, Giulia,Burke, Sarah J.,Colandrea, Rebecca C.,Sadowski, Nicholas R.,Figula, Bryan C.,Tomsho, John W.
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p. 6193 - 6201
(2018/05/15)
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- An Efficient Benzoxaborole One-Pot Synthesis by SiliaCat DPP-Pd Heterogeneous Catalysis using Diboronic Acid
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Organoboron compounds are valuable molecules of increasing interest in organic synthesis, catalysis, biology and medicine. Among them, benzoxaboroles emerged as promising building blocks for numerous research programs. In this letter, we communicate the development of new conditions for the one-pot benzoxaborole synthesis by SiliaCat DPP?Pd catalysis using diboronic acid as the boron source. This low cost and sustainable strategy permitted the preparation of a useful range of benzoxaborole building blocks. Finally, the transformation was extended to a continuous flow process using our Vapourtec system. (Figure presented.).
- Kunihiro, Kana,Dumais, Laurence,Lafitte, Guillaume,Varvier, Emeric,Tomas, Lo?c,Harris, Craig S.
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supporting information
p. 2757 - 2761
(2018/06/04)
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- A convenient one-pot synthesis of boroxoles from diboronic acid
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The preparation of the boroxole motif traditionally relies on a 3-step process and the use of n-butyl lithium that can limit substrate scope. Herein during our exploration toward novel RORγ inhibitors, we identified a convenient one-pot preparation of the motif in good yields with good substrate scope.
- Lafitte, Guillaume,Kunihiro, Kana,Bonneaud, Céline,Dréan, Bénédicte,Gaigne, Frédéric,Parnet, Véronique,Pierre, Romain,Raffin, Catherine,Vatinel, Rodolphe,Fournier, Jean-Fran?ois,Musicki, Branislav,Ouvry, Gilles,Bouix-Peter, Claire,Tomas, Loic,Harris, Craig S.
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supporting information
p. 3757 - 3759
(2017/09/12)
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- FUNCTIONALIZED AMINOBENZOBOROXOLES
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Disclosed are functionalized aminobenzoboroxoles compounds, method for preparing these compounds, and methods for treating cancers.
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-
Paragraph 0105
(2017/03/14)
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- Benzoborate synthesis method
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The present invention relates to a benzoborate synthesis method, which comprises that under the protection of nitrogen, o-halo aryl alcohol and bis(pinacolato)diboron are adopted as reaction substrates, and a Miyaura coupling series connection reaction is performed for 12-16 h at a temperature of 80-110 DEG C under catalysis of palladium to perform one-step synthesis of a multi-substituted or multi-functionalized benzoborate compound, wherein the palladium catalyst is bistriphenylphosphinepalladium bichloride, a mixture comprising palladium acetate and 1,1'-bis(diphenylphosphine)ferrocene according to a molar ratio of 1:2, tetrakistriphenylphosphine palladium or 1,1'-bis(diphenylphosphine)ferrocene palladium dichloride, a molar ratio of the reaction substrate o-halo aryl alcohol to the reaction substrate bis(pinacolato)diboron to the palladium catalyst to the alkali is 1:1.2-1.5:0.05-0.1:3-6. The synthesis method of the present invention has characteristics of simple process and high product yield.
- -
-
Paragraph 0100-0102
(2016/11/24)
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- Synthesis and evaluation of functionalized benzoboroxoles as potential anti-tuberculosis agents Dedicated to Professor Neil K. Garg on the occasion of his receipt of the Tetrahedron Young Investigator Award
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Several derivatives of aminobenzoboroxole have been prepared starting from 2-boronobenzaldehyde. All of these derivatives have been evaluated for their anti-mycobacterial activity on Mycobacterium smegmatis and cytotoxicity on breast cancer cell line MCF7. Based on these studies, all the tested molecules have been found to be generally non-toxic and benzoboroxoles with unsubstituted (primary) amines have been found to exhibit good anti-mycobacterial activity. Some of the key compounds have been evaluated for their anti-tubercular activity on Mycobacterium tuberculosis H37Rv using 7H9 and GAST media. 7-Bromo-6-aminobenzoboroxole 4 has been identified as the lead candidate compound for further development.
- Alam, Mohammad A.,Arora, Kriti,Gurrapu, Shirisha,Jonnalagadda, Sravan K.,Nelson, Grady L.,Kiprof, Paul,Jonnalagadda, Subash C.,Mereddy, Venkatram R.
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p. 3795 - 3801
(2016/06/06)
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- One-pot synthesis of benzoxaborole derivatives from the palladium-catalyzed cross-coupling reaction of alkoxydiboron with unprotected o-bromobenzylalcohols
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Under very mild conditions, functionalized benzoxaborole derivatives were prepared in good to excellent yields via a palladium-catalyzed Miyaura borylation reaction of readily available unprotected o-bromobenzylalcohols, and bis(pinacolato)diboron (B2pin2) without the assistance of an acid. Blue-light-emitting materials based on spiro benzoxaborole building blocks have been obtained with potential applications in organic electronics and biomedicine.
- Zhu, Jianan,Wei, Ying,Lin, Dongqing,Ou, Changjin,Xie, Linghai,Zhao, Yu,Huang, Wei
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p. 11362 - 11368
(2015/11/27)
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- Synthesis and evaluation of functionalized aminobenzoboroxoles as potential anti-cancer agents
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Several aminobenzoboroxole derivatives have been prepared starting from o-boronobenzaldehyde employing reductive amination protocol. The corresponding aminobenzoboroxole derivatives have been further functionalized as N-nitrosoaminobenzoboroxoles as well as N-benzoboroxolylureas. These derivatives have been evaluated for their anti-cancer activity on human pancreatic cancer MIAPaCa-2 and human breast cancer MDA-MB-231 cell lines. 2015 Elsevier Ltd. All rights reserved.
- Suman, Pathi,Patel, Bhawankumar P.,Kasibotla, Agasthya V.,Solano, Lucas N.,Jonnalagadda, Subash C.
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p. 125 - 131
(2015/12/18)
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- Benzoxaborolate ligands in group 13 metal complexes
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A series of group 13 metal benzoxaborolates [R2MOB(o-CH 2O)(C6H4)]2 [R = tBu, M = Al (2), R = Me, M = Ga (3), R = tBu, M = Ga (4), R = tBu, M = In (5)] were synthesize
- Ja?kowska, Eliza,Justyniak, Iwona,Cyrański, Micha? K.,Adamczyk-Wo?niak, Agnieszka,Sporzyński, Andrzej,Zygad?o-Monikowska, Ewa,Ziemkowska, Wanda
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- A divalent protecting group for benzoxaboroles
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1-Dimethylamino-8-methylaminonaphthalene is put forth as a protecting group for benzoxaboroles. The ensuing complex is fluorescent, charge-neutral, highly stable under basic conditions, stable to anhydrous acid, and readily cleavable in aqueous acid to return the free benzoxaborole. The Royal Society of Chemistry 2013.
- Vanveller, Brett,Aronoff, Matthew R.,Raines, Ronald T.
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p. 21331 - 21334
(2013/11/06)
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- Substituent effects on oxidation-induced formation of quinone methides from arylboronic ester precursors
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A series of arylboronic esters containing different aromatic substituents and various benzylic leaving groups (Br or N+Me3Br -) have been synthesized. The substituent effects on their reactivity with H2O2 and formation of quinone methide (QM) have been investigated. NMR spectroscopy and ethyl vinyl ether (EVE) trapping experiments were used to determine the reaction mechanism and QM formation, respectively. QMs were not generated during oxidative cleavage of the boronic esters but by subsequent transformation of the phenol products under physiological conditions. The oxidative deboronation is facilitated by electron-withdrawing substituents, such as aromatic F, NO2, or benzylic N+Me 3Br-, whereas electron-donating substituents or a better leaving group favor QM generation. Compounds containing an aromatic CH 3 or OMe group, or a good leaving group (Br), efficiently generate QMs under physiological conditions. Finally, a quantitative relationship between the structure and activity has been established for the arylboronic esters by using a Hammett plot. The reactivity of the arylboronic acids/esters and the inhibition or facilitation of QM formation can now be predictably adjusted. This adjustment is important as some applications may benefit and others may be limited by QM generation. Tunable quinone methide formation: Aromatic substituents and the benzylic leaving group strongly affect the H 2O2-induced formation of quinone methides (QMs) from arylboronic esters (see scheme). The reactivity of arylboronic esters can be predictably adjusted by varying substituents. Copyright
- Cao, Sheng,Christiansen, Robin,Peng, Xiaohua
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p. 9050 - 9058
(2013/07/26)
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- Examination of the reactivity of benzoxaboroles and related compounds with a cis -diol
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Benzoxaboroles have been emerging as an interesting and useful scaffold in drug discovery due to their apparently unique reactivity toward diols under physiological conditions. In this work, the reaction of benzoxaborole with the diol-containing, fluorescent dye Alizarin Red S is probed. Steady-state and presteady-state experiments have been conducted for the characterization of the reactions over a wide range of pH. Results indicate that Alizarin Red S reacts with both the boronic (neutral, trigonal) form as well as the boronate (anionic, tetrahedral) form of benzoxaborole in a reaction largely analogous to that previously determined for the simple phenylboronic acid. However, in certain key aspects, the reactivity of the benzoxaborole was found to differ from that of simple phenylboronic acid. The structural origin of these differences has been explored by examination of compounds related to both benzoxaborole and phenylboronic acid. These results may be applied to rational drug discovery efforts aimed at expanding the use of benzoxaboroles in medicine.
- Tomsho, John W.,Benkovic, Stephen J.
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p. 11200 - 11209
(2013/03/14)
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- Amination-reduction reaction as simple protocol for potential boronic molecular receptors. Insight in supramolecular structure directed by weak interactions
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The synthesis of the potential molecular receptors in the amination-reduction reaction has been investigated within the model system comprising (2-formylphenyl)boronic acid and morpholine. The 3-amine substituted benzoxaborole was identified to be the intermediate of the synthesis and the unsubstituted benzoxaborole as the by-product resulting from reduction of the starting material. The insight into the reactivity of the starting materials as well as the intermediate benzoxaborole enabled significant rise in the yield of 2-(aminomethyl) phenylboronic acids synthesis. The solid state structure of 2-(piperidylmethyl)phenylboronic acid has been re-determined, and the description of the molecule and the crystal is given. The supramolecular layer structure directed by the weak C-H...O and C-H...π interactions was identified and scrutinized based on the geometry and Hirshfeld surface analyses. Versita Sp. z o.o.
- Adamczyk-Wo?niak, Agnieszka,Madura, Izabela,Pawe?ko, Alicja,Sporzyński, Andrzej,?ubrowska, Anna,?y?a, Jacek
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experimental part
p. 199 - 205
(2012/02/06)
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- Reactivity of 2-formylphenylboronic acid toward secondary aromatic amines in amination-reduction reactions
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The synthesis of 2-(arylaminomethyl)phenylboronic acid via an amination-reduction reaction has been investigated within a model system comprising 2-formylphenylboronic acid and N-ethylaniline. Adoption of the appropriate reaction conditions influences the reactivity of 2-formylphenylboronic acid, enabling efficient synthesis of so-far unobtainable 2-(arylaminomethyl)phenylboronic compounds. The first crystal structure of the aromatic amine derivative has been determined and described.
- Adamczyk-Wo?niak, Agnieszka,Fratila, Raluca M.,Madura, Izabela D.,Pawe?ko, Alicja,Sporzyński, Andrzej,Tumanowicz, Marta,Velders, Aldrik H.,Y?a, Jacek
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experimental part
p. 6639 - 6642
(2012/01/14)
-
- Influence of the substituents on the structure and properties of benzoxaboroles
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Benzoxaboroles possessing aryl substituents in the oxaborole ring were synthesized, and their structures were detennined by single-crystal X-ray diffraction. Structures in the solid state are centrosymmetric dimers with two intermolecular hydrogen bonds. These compounds were investigated using a combination of the spectroscopic and the computational approach, comparing their properties with the unsubstituted compound. Investigated compounds were characterized by 1H, 13C, and 11B NMR spectroscopy in solution. Assignment of 1H and 13C signals was made on the basis of HSQC and HMBC spectra. The molecular structure of 1,3dihydro-1-hydroxy-3-phenyl-2,1-benzoxaborole was calculated by the density functional (B3LYP) method with the extended 6-311++G(d,p) basis set. The calculated geometrical parameters were compared with experimental X-ray data, and the differences between experimental and calculated values were found to be of the order of experiment standard deviation, confirming a good description by this level of theory. The harmonic frequencies, potential energy distribution (PED), and IR intensities of this compound and its deuterated analogue were calculated with the B3LYP method. The assignment of the experimental spectra was made on the basis of the calculated PED. The consequence of dimer formation is the splitting of the vibrational modes into symmetric and antisymmetric vibrations. The structure modification resulting from the hydrogen bonded dimers formation is presented.
- Adamczyk-Wozniak, Agnieszka,Cyranski, Michal K.,Jakubczyk, Michal,Klimentowska, Paulina,Koll, Aleksander,Kolodziejczak, Jerzy,Pojmaj, Grzegorz,Zubrowska, Anna,Zukowska, Grazyna Z.,Sporzynski, Andrzej
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scheme or table
p. 2324 - 2330
(2010/08/04)
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- BORON-CONTAINING SMALL MOLECULES AS ANTI-INFLAMMATORY AGENTS
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Methods of treating anti-inflammatory conditions through the use of boron-containing small molecules are disclosed.
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Page/Page column 41
(2008/06/13)
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- Compounds for the Treatment of Periodontal Disease
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Compounds, compositions and methods are provided which are useful in the treatment of periodontal disease.
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Page/Page column 44
(2008/06/13)
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- Practical synthesis and applications of benzoboroxoles
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A convenient one-pot synthesis of benzoboroxoles has been developed via the reaction of o-bromobenzyl alcohols with NaH, nBuLi, and B(OiPr)3 followed by acidic hydrolysis. Applications of these benzoboroxoles have been demonstrated in Pd-catalyzed cross-coupling reactions and the protocol has been extended for the synthesis of a chiral benzoboroxole. Exceptionally short synthesis of a potent antifungal agent AN2690 and several of its analogs has also been realized.
- Gunasekera, Dinara S.,Gerold, Dennis J.,Aalderks, Nathan S.,Chandra, J. Subash,Maanu, Christiana A.,Kiprof, Paul,Zhdankin, Viktor V.,Reddy, M. Venkat Ram
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p. 9401 - 9405
(2008/02/13)
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- Boron-containing small molecules
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This invention relates to compounds useful for treating fungal infections, more specifically topical treatment of onychomycosis and/or cutaneous fungal infections. This invention is directed to compounds that are active against fungi and have properties that allow the compound, when placed in contact with a patient, to reach the particular part of the skin, nail, hair, claw or hoof infected by the fungus. In particular the present compounds have physiochemical properties that facilitate penetration of the nail plate.
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Page/Page column 28
(2008/06/13)
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- Synthesis and structure of benzoboroxoles: Novel organoboron heterocycles
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Benzoboroxoles (5) can be prepared from the readily available o-bromobenzyl alcohols via dilithiation followed by reaction with triisopropylborate. X-Ray structural analysis of 1-hydroxy-3(1H)-1,2-benzoboroxole (5a) as well as the results of ab initio molecular orbital calculations indicate a planar structure of the boron center with a relatively short C-B bond. Preliminary results regarding the chemistry of benzoboroxoles are also reported.
- Zhdankin, Viktor V.,Persichini III,Zhang, Lu,Fix, Shannon,Kiprof, Paul
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p. 6705 - 6708
(2007/10/03)
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- N-Isoxazolyl-biphenylsulfonamide derivatives, their preparation and their use as endothelin antagonists
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A compound of the formula I an enantiomer, diastereomer or pharmaceutically acceptable salt thereof, wherein: one of X and Y is N and the other is O; R2,R3,R4 and R5 are each independently (a) hydrogen;(b) alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, aryloxy, aralkyl or aralkoxy, any of which may be substituted with Z1, Z2 and Z3;(c) halo;(d) hydroxyl;(e) cyano;(f) nitro;(g)-C(O)H or-C(O)R6;(h)-CO2H or-CO2R6;(i)-SH,-S(O)nR6 ,-S(O)m-OH,-S(O)m-OR6,-O-S(O)m-R6,-O-S(O)mOH or-O-S(O)m-OR6;(j)-Z4-NR7R8; or(k)-Z4-N(R11)-Z5-NR9 R10; R4 and R5 together are alkylene or alkenylene, either of which may be substituted with Z1,Z2 and Z3, completing a 4-to 8-membered saturated, unsaturated or aromatic ring together with the carbon atoms to which they are attached; G1 is (a) hydrogen; or(b) alkyl; G2 is (a) hydroxyalkyl;(b)-(CH2)mOR6; or(c)-(CH2)m-NR12 R13;(d) mono-to hexa-halo substituted alkyl; or(e)-(CH2)n OR14; and the remaining symbols are as defined in the description.The compounds of formula I are antagonists of ET-1, ET-2 and /or ET-3 and are useful in treatment of conditions associated with increased ET levels (e.g., dialysis, trauma and surgery) and of all endothelin-dependent disorders. They are thus inter alia useful as antihypertensive agents.
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