- ALLOSTERIC CHROMENONE INHIBITORS OF PHOSPHOINOSITIDE 3-KINASE (PI3K) FOR THE TREATMENT OF DISEASES ASSOCIATED WITH P13K MODULATION
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The disclosure relates to compounds of Formula (I) as allosteric chromenone inhibitors of phosphoinositide 3-kinase (PI3K) useful in the treatment of diseases or disorders associated with PI3K modulation, Formula (I), or a prodrug, solvate, enantiomer, st
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- Redox-Neutral Coupling between Two C(sp3)?H Bonds Enabled by 1,4-Palladium Shift for the Synthesis of Fused Heterocycles
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The intramolecular coupling of two C(sp3)?H bonds to forge a C(sp3)?C(sp3) bond is enabled by 1,4-Pd shift from a trisubstituted aryl bromide. Contrary to most C(sp3)?C(sp3) cross-dehydrogenative couplings, this reaction operates under redox-neutral conditions, with the C?Br bond acting as an internal oxidant. Furthermore, it allows the coupling between two moderately acidic primary or secondary C?H bonds, which are adjacent to an oxygen or nitrogen atom on one side, and benzylic or adjacent to a carbonyl group on the other side. A variety of valuable fused heterocycles were obtained from easily accessible ortho-bromophenol and aniline precursors. The second C?H bond cleavage was successfully replaced with carbonyl insertion to generate other types of C(sp3)-C(sp3) bonds.
- Rocaboy, Ronan,Anastasiou, Ioannis,Baudoin, Olivier
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supporting information
p. 14625 - 14628
(2019/09/16)
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- Contributions of inner and outer coordination sphere bonding in determining the strength of substituted phenolic pyrazoles as copper extractants
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Alkyl-substituted phenolic pyrazoles such as 4-methyl-2-[5-(n-octyl)-1H-pyrazol-3-yl]phenol (L2H) are shown to function as Cu-extractants, having similar strength and selectivity over Fe(iii) to 5-nonylsalicylaldoxime which is a component of the commercially used ACORGA solvent extraction reagents. Substitution in the phenol ring of the new extractants has a major effect on their strength, e.g. 2-nitro-4-methyl-6-[5-(2,4,4-trimethylpentyl)-1H-pyrazol-3-yl]phenol (L4H) which has a nitro group ortho to the phenolic hydroxyl group unit and has an extraction distribution coefficient for Cu nearly three orders of magnitude higher than its unsubstituted analogue 4-methyl-6-[5-(2,4,4-trimethylpentyl)-1H-pyrazol-3-yl]phenol (L8H). X-ray structure determinations and density functional theory (DFT) calculations confirm that inter-ligand hydrogen bonding between the pyrazole NH group and the phenolate oxygen atom stabilise the Cu-complexes, giving pseudomacrocyclic structures. Electron-accepting groups ortho to the phenol oxygen atoms buttress the inter-ligand H-bonding, enhancing extractant strength but the effectiveness of this is very dependent on steric factors. The correlation between the calculated energies of formation of copper complexes in the gas phase and the observed strength of comparably substituted reagents in solvent extraction experiments is remarkable. Analysis of the energies of formation suggests that big differences in strength of extractants arise principally from a combination of the effects of the substituents on the ease of deprotonation of the proligands and, for the ortho-substituted ligands, their propensity to buttress inter-ligand hydrogen bonding.
- Healy, Mary R.,Roebuck, James W.,Doidge, Euan D.,Emeleus, Lucy C.,Bailey, Philip J.,Campbell, John,Fischmann, Adam J.,Love, Jason B.,Morrison, Carole A.,Sassi, Thomas,White, David J.,Tasker, Peter A.
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supporting information
p. 3055 - 3062
(2016/02/19)
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- Catalyst Compounds and Use Thereof
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This invention relates to Group 4 catalyst compounds containing di-anionic tridentate nitrogen/oxygen based ligands. The catalyst compounds are useful, with or without activators, to polymerize olefins, particularly a-olefins, or other unsaturated monomers. Systems and processes to oligomerize and/or polymerize one or more unsaturated monomers using the catalyst compound, as well as the oligomers and/or polymers produced therefrom are also provided.
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- Radical-scavenging polyphenols: New strategies for their synthesis
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New strategies for the synthesis of polyphenols, compounds with antioxidant properties contained in every kind of plants, are discussed. Syntheses of different classes of polyphenols, namely ubiquinones, present in many natural systems in which electron-transfer mechanisms are involved, hydroxytyrosol, one of the main components of the phenol fraction in olives, and flavonoids, widespread in the plant kingdom, were approached by simple and environmentally sustainable methods.
- Bovicelli, Paolo
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p. 1703 - 1710
(2008/03/11)
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- (Hetero)aryl-bicyclic heteroaryl derivatives, their preparation and their use as protease inhibitors
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The present invention provides novel compounds of the Formula (I): A-B, its prodrug forms, or pharmaceutically acceptable salts thereof, wherein A represents a saturated, unsaturated, or a partially unsaturated bicyclic heterocyclic ring structure, and B represents an aryl or a heteroaryl group. Preferred compounds of the present invention comprise a benzimidazole or indole nucleus. The compounds of this invention are inhibitors of serine proteases, Urokinase (uPA), Factor Xa (FXa), and/or Factor VIIa (FVIIa), and have utility as anti cancer agents and/or as anticoagulants for the treatment or prevention of thromboembolic disorders in mammals.
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Page/Page column 69
(2010/02/11)
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- New convenient synthesis of iridol. An approach to the synthesis of ubiquinones
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A strategy for the synthesis of ubiquinones, in which iridol is the key intermediate, has been developed, together with a new convenient synthesis of iridol (2,3-dimethoxy-5-methylphenol) starting from the easily available 4-methylphenol and using mild conditions and friendly and high-yielding reactions.
- Bovicelli, Paolo,Antonioletti, Roberto,Barontini, Maurizio,Borioni, Giorgio,Bernini, Roberta,Mincione, Enrico
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p. 1255 - 1257
(2007/10/03)
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- Pyridinium bromochromate: A new and efficient reagent for bromination of hydroxy aromatics
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Pyridinium bromochromate (PBC) has been used as an efficient and selective nuclear brominating agent for bromination of various substituted hydroxy-acetophenones, aldehydes and phenols.
- Patwari, Shivaji B.,Baseer, Mohammad A.,Vibhute, Yashwant B.,Bhusare, Sudhakar R.
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p. 4893 - 4894
(2007/10/03)
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- Synthetic studies of the phosphatidylinositol 3-kinase inhibitor LY294002 and related analogues
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Synthetic methodologies have been developed for the direct and high-yielding preparation of the phosphatidyl-inositol 3-kinase inhibitor LY294002. These methods are readily amenable to the efficient generation of analogues, which will facilitate a detailed investigation of this important family of enzymes.
- Abbott, Belinda,Thompson, Philip
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p. 1099 - 1106
(2007/10/03)
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- Reaction of 4-(2′-hydroxyaryl)-1,3-dithiolium salts with sodium sulfide. A selective synthesis of 2′-hydroxyacetophenones
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The treatment of 4-(2′-hydroxyaryl)-2-(N,N-dialkylamino)-1,3-dithiolium perchlorates (1a-g) with sodium sulfide nonahydrate in ethanol at room temperature affords the corresponding 1,3-dithiole-2-thiones (2a-g). When these reactions are conducted in boiling ethanol, 2′-hydroxyacetophenones (3a-g) have been obtained in good to excellent yield. A tentative mechanism for the formation of 3a-g shows that this reaction is regioselective, this being established by the presence of hydroxyl group in 2′-position. That has been confirmed in a control experiment, 4-phenyl-2-(piperidin-1-yl)-1,3-dithiolium perchlorate affording a mixture of condensation products of acetophenone and phenylacetaldehyde, under similar reaction conditions.
- Birsa, Mihail Lucian
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p. 3071 - 3076
(2007/10/03)
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- Development of serine protease inhibitors displaying a multicentered short (<2.3 ?) hydrogen bond binding mode: Inhibitors of urokinase-type plasminogen activator and factor Xa
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Novel scaffolds that bind to serine proteases through a unique network of short hydrogen bonds to the catalytic Ser195 have been developed. The resulting potent serine protease inhibitors were designed from lead molecule 2-(2-hydroxyphenyl)1H-benzoimidazo
- Verner,Katz,Spencer,Allen,Hataye,Hruzewicz,Hui,Kolesnikov,Li,Luong,Martelli,Radika,Rai,She,Shrader,Sprengeler,Trapp,Wang,Young,Mackman
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p. 2753 - 2771
(2007/10/03)
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- Use of Pyrylium Synthons in the Synthesis of Hemispherands with Modified Cavities. X-ray Structures of the 21-Hemispherand and a Pyrido Hemispherand
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The effect of variation of the rigid part of the parent Cram hemispherand 1a on the preorganization of the macrocyclic cavity has been studied.Four novel 18-membered hemispherands (3,4a-c)have been synthesized via a novel multistep route using 2,6-di- and
- Dijkstra, Pieter J.,Hertog, Herman J. den,Steen, Bart J. van,Zijlstra, Sietze,Skowronska-Ptasinska, Maria
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p. 2433 - 2442
(2007/10/02)
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- THE SYNTHESIS OF 4H-PYRAN CONTAINING HEMISPHERANDS VIA PYRYLIUM SALTS
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Two new hemispherands 2a and 2b containing a central 4H-pyran unit were synthesized via appropiately substituted 2,6-phenyl pyrylium salts; largest ΔG0 values of complexation of 2a and 2b with different alkali picrates are found for Na(+) and K(+).
- Dijkstra, P. J.,Steen, B. J. van,Hams, B. H. M.,Hertog, H. J. den,Reinhoudt, D. N.
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p. 3183 - 3186
(2007/10/02)
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- Protonation Constants and Thermodynamic Parameters of 3-Bromo-2-Hydroxy-5-Methylacetophenone, Its Oxime and n-Propylimine
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Potentiometric studies have been carried out on 3-bromo-2-hydroxy-5-methylacetophenone, its oxime and n-propylimine in dioxane-water (20 to 75percent, v/v) media at different ionic strengths 0.02M, 0.05M and 0.1M (NaClO4) and temperatures 25, 30 and 35 de
- Verma, J. K.,Patel, R. B.
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