- DIRECT INHIBITORS OF KEAP1-NRF2 INTERACTION AS ANTIOXIDANT INFLAMMATION MODULATORS
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A method of identifying compounds as direct inhibitors of Keap1-Nrf2 interaction through high-throughput screening and lead development. The direct inhibitors of Keap1-Nrf2 interaction are more specific and free of various undesirable effects than existing indirect inhibitors, and are potential drug candidates of chemopreventive and therapeutic agents for treatment of various diseases or conditions involving oxidative stress and/or inflammation, including but not limited to cancers, diabetes, Alzheimer's, and Parkinson's. Novel compounds are identified and methods of preventing or treating diseases or conditions related to Keap1-Nrf2 interaction activity by use of the novel compounds identified or compositions containing such compounds are also disclosed.
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Paragraph 0413-0414
(2018/06/09)
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- Palladium-Catalyzed β-Mesylation of Simple Amide via Primary sp3 C-H Activation
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A β-mesylation of primary sp3 C-H bonds from simple amides with methanesulfonic anhydride (Ms2O) has been established successfully at 80 °C in a Pd(OAc)2 (catalyst)/K2S2O8 (oxidant)/CF3CH2OH (solvent) system. These amide substrates involve N-monosubstituted linear, branch, or cyclic alkanes, and electron-deficient benzyl compounds. The β-mesylated amide products can be converted easily to β-fluoroamides or β-lactams through inter- or intramolecular SN2 processes.
- Zhao, Ren,Lu, Wenjun
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supporting information
p. 1768 - 1771
(2017/04/11)
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- DIRECT INHIBITORS OF KEAP1-NRF2 INTERACTION AS ANTIOXIDANT INFLAMMATION MODULATORS
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A method of identifying compounds as direct inhibitors of Keap1-Nrf2 interaction through high-throughput screening and lead development. The direct inhibitors of Keap1-Nrf2 interaction are more specific and free of various undesirable effects than existing indirect inhibitors, and are potential drug candidates of chemopreventive and therapeutic agents for treatment of various diseases or conditions involving oxidative stress and/or inflammation, including but not limited to cancers, diabetes, Alzheimer's, and Parkinson's. Novel compounds are identified and methods of preventing or treating diseases or conditions related to Keapl-Nrf2 interaction activity by use of the novel compounds identified or compositions containing such compounds are also disclosed.
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Page/Page column 78; 79
(2013/05/22)
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- 4- [HETEROCYCLYL-METHYL] -8-FLUORO-QUINOLIN-2-ONES USEFUL AS NITRIC OXIDE SYNTHASE INHIBITORS
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Novel compounds of formulae (II, III) and pharmaceutical compositions have been found to inhibit inducible NOS synthase wherein: R4, R5, R6 and R7 are independently selected from the group consisting of hydrogen, lower alkyl, and halogen; and, R8 has the structure whrein X1, X2, X3, X4, X5, X6, R9, R13, R14 and n are as described herein.
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Page/Page column 53
(2009/04/25)
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- Di-μ-hydroxy-bis(N,N,N′,N′-tetramethylenediamine)-copper(II) chloride [Cu(OH)·TMEDA]2Cl2: An efficient, practical catalyst for benzylation and allylation of amides
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An efficient protocol for the benzylation or allylation of amides using the corresponding benzyl or allyl chlorides as electrophiles under basic conditions with commercially available 5 mol % of [Cu(OH)TMEDA]2Cl2 as catalyst was developed. Under these conditions, unprotected amino acids were benzylated without any racemization.
- Kumaraswamy,Pitchaiah,Ramakrishna,Ramakrishna,Sadaiah
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p. 2013 - 2015
(2007/10/03)
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- Aniline derivatives possessing an inhibitory effect of nitric oxide synthase
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Compounds represented by the general formula (1): ? (where R1is SR6or NR7R8, where R6is typically an alkyl group having 1-6 carbon atoms, R7is a hydrogen atom, an alkyl group having 1-6 carbon atoms or a nitro group, and R8is a hydrogen atom or an alkyl group having 1-6 carbon atoms; R2and R3are each typically a hydrogen atom or an alkyl group having 1-6 carbon atoms; R4is a hydrogen atom, an alkyl group having 1-6 carbon atoms or an amidino group of which the amine portion may be substituted by an alkyl or nitro group; R5is a hydrogen atom or an alkyl group having 1-6 carbon atoms; Y1, Y2, Y3and Y4which may be the same or different are each typically a hydrogen atom, a halogen atom or an alkoxy group having 1-6 carbon atoms; n and m are each an integer of 0 or 1), or possible stereoisomers or optically active forms of the compounds or pharmaceutically acceptable salts thereof. The compounds possess a potent nitric oxide synthase inhibiting activity and are useful as therapeutics of cerebrovascular diseases.
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- Benzylphthalimides and phenethylphthalimides with thalidomide-like activity on the production of tumor necrosis factor α
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Benzylphthalimide analogs (P1P's) and phenethylphthalimide analogs (P2P's) have been found to exhibit thalidomide-like activity on the production of tumor necrosis factor (TNF)-α by the human leukemia cell line, HL-60, stimulated by 12-O-tetradecanoylphorbol-13-acetate (TPA). Structure-activity relationships are discussed on the basis of the TNF-α production-enhancing activity. Benzylphthalimide (P1P-00) exhibited activity which is weaker than that of thalidomide, but introduction of a methyl group at the ortho-position of the benzyl moiety (P1P-10) resulted an increase to a level comparable with that of thalidomide. Phenethylphthalimide (P2P-00) is more potent than thalidomide, and its fluorinated derivative, 2-phenethyl-4,5,6,7-tetrafluoro- 1H-isoindole-1,3-dione (FP2P-00), exhibited potent activity at very low concentrations.
- Sasaki,Shibata,Hashimoto,Iwasaki
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p. 1228 - 1233
(2007/10/03)
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- Electrochemical reduction of N-(o-nitrobenzoyl) and N-(o-nitrobenzyl)-amides or imides. Electrosynthesis of quinazoline derivatives.
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Controlled potential electrolysis at a mercury pool cathode, carried out at the plateau of the first reduction wave of o-nitrobenzoylacetamide, leads to 4-hydroxy-2-methylquinazoline 1-oxide, resulting from a ring closure of the phenylhydroxylamine intermediate.In the same conditions, o-nitrobenzoylsuccinimide gives rise to a tricyclic compound which undergoes a nucleophilic attack from the electrolysis medium, with formation of 4-hydroxyquinazoline 1-oxide bearing at the position 2, either a propanoate group (acidic media) or a propanamido group (ammoniacal buffer).At last, the hydroxylamino derivative issued from o-nitrobenzoyl- phtalimide reduction, disproportionates in acidic medium and a mixture of 2-(o-carboxyphenyl)-4-hydroxyquinazoline 1-oxide and of the parent quinazoline is obtained at the term of the electrolysis.As a matter of comparison, the parent o-nitrobenzyl substrates have been studied; no ring closure occurs at the hydroxylamino stage but quinazoline derivatives can be obtained from the corresponding anilines by electroreduction at more negative potentials. Key words: polarography / cyclic voltammetry / controlled potential electrolysis / quinazoline 1-oxyde / quinazoline
- Chibani, A.,Hazard, R.,Tallec, A.
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p. 814 - 822
(2007/10/02)
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- Piperazinopyrrolobenzodiazepines
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1,3,4,14b-Tetrahydro-2H,10H-pyrazino[1,2-a]pyrrolo[2,1-c][1,4]benzodiazepines, e.g. those of the formula STR1 R6 =H, alkyl, alkenyl, alkynyl, (cycloalkyl or HO)-alkyl R7 =H, halo or CF3 acyl derivatives, N-oxides, quaterna
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- NMR STUDIES ON IMIDINES. I. AN 1H AND 13C NMR STUDY OF 10,12-DIHYDROISOINDOLOQUINAZOLINE-12-ONE
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10,12-Dihydroisoindoloquinazoline-12-one (5) was prepared and fully examined by 1H and 13C NMR spectroscopy in CDCl3 and DMSO-d6 solution.
- Spiessens, Luc I.,Anteunis, Marc J. O.
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p. 1167 - 1176
(2007/10/02)
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