- CHEMICAL COMPOUNDS
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The invention is directed to substituted salicylamide derivatives. Specifically, the invention is directed to compounds according to FormμLa (I): wherein R, R1,P, X, Y, and Z are as defined herein; or a pharmaceutically acceptable salt thereof. The compounds of the invention are inhibitors of CD73 and can be usefμL in the treatment of cancer, pre-cancerous syndromes and diseases associated with CD73 inhibition, such as AIDS, the treatment of HIV, autoimmune diseases, infections, atherosclerosis, and ischemia–reperfusion injury. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting CD73 activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.
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Page/Page column 177
(2019/04/11)
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- SUBSTITUTED N-HYDROXYAMIDINOHETEROCYCLES AS MODULATORS OF INDOLEAMINE 2,3- DIOXYGENASE
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The invention provides modulators of indoleamine 2,3-dioxygenase (IDO1) and their use in the prophylaxis and/or treatment of IDO1-mediated diseases. Specifically, the present invention provides compounds according to Formula (I) an enantiomer, diastereomer, tautomer or pharmaceutically acceptable salt thereof.
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Page/Page column 52
(2018/05/24)
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- Antiproliferative activity and SARs of caffeic acid esters with mono-substituted phenylethanols moiety
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A series of CAPE derivatives with mono-substituted phenylethanols moiety were synthesized and evaluated by MTT assay on growth of 4 human cancer cell lines (Hela, DU-145, MCF-7 and ECA-109). The substituent effects on the antiproliferative activity were systematically investigated for the first time. It was found that electron-donating and hydrophobic substituents at 2′-position of phenylethanol moiety could significantly enhance CAPE's antiproliferative activity. 2′-Propoxyl derivative, as a novel caffeic acid ester, exhibited exquisite potency (IC50?=?0.4?±?0.02 & 0.6?±?0.03?μM against Hela and DU-145 respectively).
- Xie, Jin,Yang, Fengzhi,Zhang, Man,Lam, Celine,Qiao, Yixue,Xiao, Jia,Zhang, Dongdong,Ge, Yuxuan,Fu, Lei,Xie, Dongsheng
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supporting information
p. 131 - 134
(2016/12/27)
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- QUINOLONE DERIVATIVES AS FIBROBLAST GROWTH FACTOR RECEPTOR INHIBITORS
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Compounds of formula (I) that are Fibroblast Growth Factor Inhibitors (FGFR) and are therefore useful for the treatment of diseases treatable by inhibition of FGFR are disclosed. Also disclosed are pharmaceutical compositions containing such compounds and processes for preparing such compounds.
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- N, N-disubstituted benzo-nitrogen heterocycles-2-amine compound and use thereof
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The invention mainly relates to an N,N-double substituted benzoazacyclo-2-amide compound and an application thereof. The N,N-double substituted benzoazacyclo-2-amide compound is a compound shown as formula I or a salt formed by a medical acid or alkali. The compound provided by the invention has strong inhibition activity on RhoA protease which is tightly related with cardiovascular and cerebrovascular diseases. The compound provided by the invention is hopeful to be developed into a RhoA protease small-molecule inhibitor type cardiovascular and cerebrovascular disease treatment medicine.
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Paragraph 0309-0312
(2016/10/09)
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- QUINOLONE DERIVATIVES AS FIBROBLAST GROWTH FACTOR INHIBITORS
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Compounds of formula (Ι') that are Fibroblast Growth Factor Inhibitors (FGFR) and are therefore useful for the treatment of diseases treatable by inhibition of FGFR are disclosed. Also disclosed are pharmaceutical compositions containing such compounds and processes for preparing such compounds.
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- BORON-CONTAINING SMALL MOLECULES
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This invention relates to 6-substituted benzoxaborole compounds of the following formula and their use for treating bacterial infections.
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Page/Page column 190
(2011/06/16)
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- Pd-catalyzed conversion of aryl chlorides, triflates, and nonaflates to nitroaromatics
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(Chemical Equation Presented) An efficient Pd catalyst for the transformation of aryl chlorides, triflates, and nonaflates to nitroaromatics has been developed. This reaction proceeds under weakly basic conditions and displays a broad scope and excellent
- Fors, Brett P.,Buchwald, Stephen L.
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supporting information; experimental part
p. 12898 - 12899
(2009/12/07)
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- LIGANDS FOR TRANSITION-METAL-CATALYZED CROSS-COUPLINGS, AND METHODS OF USE THEREOF
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Ligands for transition metals are disclosed herein, which may be used in various transition-metal-catalyzed carbon-heteroatom and carbon-carbon bond-forming reactions. The disclosed methods provide improvements in many features of the transition-metal-catalyzed reactions, including the range of suitable substrates, number of catalyst turnovers, reaction conditions, and efficiency. For example, improvements have been realized in transition-metal-catalyzed cross-coupling reactions.
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Page/Page column 144-145
(2009/07/17)
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- COMPOUNDS
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A compound of formula (I): compositions and medicaments containing the same as well as processes for the preparation and use of such compounds, compositions and medicaments, particularly in diseases associated with inappropriate Aurora activity.
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Page/Page column 44
(2010/11/26)
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- CHEMISTRY OF NITRO ETHERS. XVIII. SIMPLIFIED SYNTHESIS OF 2-(4-NITROPHENYL)ETHANOL
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A method was developed for the preparative synthesis of 2-(4-nitrophenyl)ethanol by the nitration of 2-phenylethanol followed by acid hydrolysis of 2-(4-nitrophenyl)ethyl nitrate.
- Kochergin, P. M.,Blinova, L. S.
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p. 1556 - 1558
(2007/10/03)
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- Phenethanolamine compounds
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The invention provides compounds of the general formula (I) STR1 wherein the substituents are defined in the specification, and physiologically acceptable salts and solvates thereof. The compounds of formula (I) have a selective stimulant action at β2 -adrenoreceptors and are useful, in particular in the treatment of diseases associated with reversible airways obstruction such as asthma and chronic bronchitis.
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- Photoaddition of Water and Alcohols to 3-Nitrostyrenes. Structure-Reactivity and Solvent Effects
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The photoadditions of water and several alcohols to the triplet excited states of 3-nitrostyrenes 1, 3-5, and 8 to give the corresponding anti-Markovnikov addition products are reported.Both 3- and 4-nitrostilbenes (6 and 7, respectively) do not undergo photoaddition on direct or sensitized irradiation in aqeous or alcohol solutions; only trans to cis photoisomerisation is observed.It is proposed that for the nitrostilbenes, efficient twisting of the alkene in the triplet excited state competes favorably with photoaddition.The efficient photoaddition of the water and methanol observed for 5-nitroindene (8)-the alkene moiety of which cannot attain an orthogonal ("twisted") state-is taken as additional evidence that these photoadditions probably occur via the planar triplet state and that twisting results in only deactivation to the ground state.The use of cosolvents (CH3CN and HCONH2) on several photoadditions is also reported.For example, use of CH3CN cosolvent in aqueous solution decreases the efficiency of photohydration in the parent 3-nitrostyrene (1) but is observed to enhance the efficiency of reaction (until about 40-70 mol percent CH3CN, depending on the substrate) for 3, 4, and 8.Quantum yields for photohydration and photoaddition of alcohols are reported for several systems.
- Wan, Peter,Davis, Michael J.,Teo, Mary-Anne
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p. 1354 - 1359
(2007/10/02)
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- ENHANCED NUCLEOPHILE SELECTIVITY IN THE PHOTOADDITION TO STYRENE. COMPARISON WITH THE THERMAL ADDITION
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The reactivity-selectivity properties of the sec-phenethyl carbenium ion and its analogues have been examined in binary-aqueous solutions of alcohols (ROH; R = Me, Et, CF3CH2, n-Bu, t-Bu, n-Pr, i-Pr), acetic acid, and in solutions containig external nucleophiles such as thiophenol, ethanethiol, acetate, and benzenesulfinate.Selectivity (S = k(Nuc)/k(H2O) is observed to be a function of the nucleophile, the ring substituent, thermal or photochemical conditions, irradiation time, and medium acidity.In the case of styrene, the photochemically generated (usually 254 nm, 1 h) species exhibits greater selectivity (up to two orders of magnitude) than its thermal counterpart, generated (usually 80 deg C, 2-4 d) in identical media, particularly in aqueous-rich solvent compositions.A rationale for these differences, supported by fluorescence quenching experiments, and the other effects upon selectivity will be discussed.
- Anderson, Steven W.,Yates, Keith
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p. 2412 - 2421
(2007/10/02)
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- Kinetic Acidity Function Hc. Part 3. Applicability to Hydration of Styrenes
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Variation of rate of hydration of substituted styrenes with acidity has been measured in aqueous sulphuric acid solutions.This reaction proceeds through a rate-limiting carbon protonation step.Linear Pfluger plots of unit slope result from the data.These appear to validate the applicability of an acidity function to the results; possible sources of error in this and related conclusions are carefully discussed.
- Ellis, Graham W. L.,Johnson, C. David
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p. 1025 - 1028
(2007/10/02)
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- Photohydration of Aromatic Alkenes and Alkynes
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The photohydrations of aromatic alkenes and alkynes 2-12 have been studied in aqueous sulfuric acid.For the nonnitro-substituted substrates 2-8, the products are the compounds obtained via Markovnikov addition of water to the alkene or alkyne moiety.Nitro-substituted styrenes 11 and 12 and phenylacetylenes 9 and 10 gave anti-Markovnikov addition products.Product quantum yields (Ψpdt) generally show a strongly sigmoidal dependence on the activity of the medium, with the exception of the nitrostyrenes, where no such dependence was observed.For compounds 2-8, quenching of fluorescence with increasing acidity was observed, and the proposed photohydration mechanism involves a rate-limiting protonation step on the first excited singlet state (S1), while for the nitrostyrenes, a rate-limiting attack of water on T1 is consistent with the available data.A mechanism involving a concerted addition of H3O+ to T1 is proposed for the photohydration of (nitrophenyl)acetylenes 9 and 10.The solvent isotope effect on the product quantum yield (ΨH/ΨD) is consistent with these proposals.Photoprotonation rate constants (kH) have been obtained - via transient and steady state measurements - for substrates 2, 4-6, and 8.Alkenes are approximately ane order of magnitude less reactive than alkynes to photoprotonation, both of which are 1011 - 1014 times more reactive than the corresponding ground-state molecules.
- Wan, Peter,Culshaw, Stephen,Yates, Keith
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p. 2509 - 2515
(2007/10/02)
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- General Base Catalysis, Structure-Reactivity interactions, and Merging of Mechanisms for Elimination Reactions of (2-Arylethyl)quinuclidinium Ions
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Structure-reactivity parameters and interaction coefficients are reported for elimination reactions of N-(2-arylethyl)quinuclidinium ions and for 2-arylethyl halides and tosylates in 60percent Me2SO/wares at 40 deg C, based on direct measurements of Bronsted β values for general base catalysis by oxyanion buffers, Hammet ρ values, and β1g for substituted quinuclidines.The Bronsted slopes increase from β - 0.67 for N-(2-(p-nitrophenyl)ethyl)quinuclidinium ions, which react by an E1cBirr mechanism, to β ca. 0.9 for the reactions of other N-(2-arylethyl)quinuclidinium ions by a concerted E2 elimination.There is no detectable interaction between the base catalyst and the leaving group for E1cB elimination, so that the interaction coefficient pxy = dβ1g/dpKBH = dβ/dpK1g is ca.0 for the N-(2-(p-nitrophenyl)ethyl)quinuclidinium ions.In contrast, values of β1g become less negative with increasing pKa of the base catalyst for the p-cyano and other N-(2-arylethyl)quinuclidinium ions, giving a constant value of pxy = 0.018 for the E2 elimination reactions of these compounds.The positive pxy coefficient for the N-(2-phenylethyl)quinuclidinium ions is confirmed by the observation of less negative values of β1g as the effective basicity of aqueous tetramethylammonium hydroxyde is increased by the addition of Me2SO.An increase in β with poorer leaving groups in the series of 2-(p-nitrophenyl)ethyl halides also corresponds to a positive pxy coefficient and an E2 mechanism.The interaction between the leaving group and central atoms is shown by the less negative values of β1g with electron-withdrawing substituents on the β-phenyl group, which corresponds to a negative coefficient pyy' = -dβ1g/d?- = -dρ/dpK1g = -0.09.A small decrease in β with electron-withdrawing substituents on the β-phenyl group suggests an interaction between the base catalyst and the central atoms that is described by a negative coefficient pxy' = dβ/d?- = dρ/dpKBH = -0.07.The sign of the pyy' and pxy' coefficient are consistent with an important component of proton transfer in the transition state.These properties of the E2 elimination reactions of N-(2-arylethyl)quinuclidinium ions can be described by a reaction coordinate that is rotated 24 deg counterclockwise from the x coordinate (for proton transfer) on a reaction coordinate-energy diagram that is defined by the observed structure-reactivity parameters.In contrast, β increases with increasing ? for elimination reactions of 2-arylethyl bromides with a positive value of pxy' = 0.07.This suggests more diagonal character to the transition state on the reaction coordinate diagram.The change from E1cB to an E2 mechanism is more easily described as a transformation of mechanism than as a change between two coexisting mechanisms.
- Gandler, Joseph R.,Jencks, William P.
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p. 1937 - 1951
(2007/10/02)
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