- PYRIMIDINYL GROUP-CONTAINING TRICYCLIC COMPOUND SERVING AS C-MET INHIBITOR
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Disclosed are a pyrimidinyl group-containing tricyclic compound and applications thereof in preparing a cancer-treating medicament. Specifically disclosed are a compound as represented by formula (I), a pharmaceutically acceptable salt of same, or an isomer thereof.
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Paragraph 0168-0170
(2021/12/18)
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- Transfer hydrogenation of aldehydes and ketones catalyzed using an aminophosphinite POCNHpincer complex of Ni(ii)
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The aminophosphinite pincer complex (POCNH)NiBr was found to effectively catalyze the transfer hydrogenation of aldehydes and ketones with 2-propanol and KOtBu as a base, presenting a rare example of bifunctional nickel transfer hydrogenation catalysts. The transfer hydrogenation of aldehydes and ketones was found to be selective, tolerating a wide range of other functional groups, including those prone to reduction, such as esters, amides, alkenes, pyridines, and nitriles. The reactions were suggested to proceedviathe metal-ligand cooperative mechanism with an intermediacy of an amido (POCN)NiIIspecies.
- ?ztop?u, ?zgür,Hayrapetyan, Davit,Khalimon, Andrey Y.,Lyssenko, Konstantin A.,Segizbayev, Medet,Shakhman, Dinmukhamed
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supporting information
p. 11950 - 11957
(2020/09/21)
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- How Metal Ion Lewis Acidity and Steric Properties Influence the Barrier to Dioxygen Binding, Peroxo O-O Bond Cleavage, and Reactivity
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Herein we quantitatively investigate how metal ion Lewis acidity and steric properties influence the kinetics and thermodynamics of dioxygen binding versus release from structurally analogous Mn-O2 complexes, as well as the barrier to Mn peroxo O-O bond cleavage, and the reactivity of Mn oxo intermediates. Previously we demonstrated that the steric and electronic properties of MnIII-OOR complexes containing N-heterocyclic (NAr) ligand scaffolds can have a dramatic influence on alkylperoxo O-O bond lengths and the barrier to alkylperoxo O-O bond cleavage. Herein, we examine the dioxygen reactivity of a new MnII complex containing a more electron-rich, less sterically demanding NAr ligand scaffold, and compare it with previously reported MnII complexes. Dioxygen binding is shown to be reversible with complexes containing the more electron-rich metal ions. The kinetic barrier to O2 binding and peroxo O-O bond cleavage is shown to correlate with redox potentials, as well as the steric properties of the supporting NAr ligands. The reaction landscape for the dioxygen chemistry of the more electron-rich complexes is shown to be relatively flat. A total of four intermediates, including a superoxo and peroxo species, are observed with the most electron-rich complex. Two new intermediates are shown to form following the peroxo, which are capable of cleaving strong X-H bonds. In the absence of a sacrificial H atom donor, solvent, or ligand, serves as a source of H atoms. With TEMPOH as sacrificial H atom donor, a deuterium isotope effect is observed (kH/kD = 3.5), implicating a hydrogen atom transfer (HAT) mechanism. With 1,4-cyclohexadiene, 0.5 equiv of benzene is produced prior to the formation of an EPR detected MnIIIMnIV bimetallic species, and 0.5 equiv after its formation.
- Yan Poon, Penny Chaau,Dedushko, Maksym A.,Sun, Xianru,Yang, Guang,Toledo, Santiago,Hayes, Ellen C.,Johansen, Audra,Piquette, Marc C.,Rees, Julian A.,Stoll, Stefan,Rybak-Akimova, Elena,Kovacs, Julie A.
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p. 15046 - 15057
(2019/10/21)
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- OX2R COMPOUNDS
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Methods and compositions for agonizing a type-2 orexin receptor (OX2R) in a cell determined to be in need thereof, including the general method of (a) administering to a subject a cyclic guanidinyl OX2R agonist and (b) detecting a resultant enhanced wakefulness or increased resistance to diet-induced accumulation of body fat, or abbreviated recovery from general anesthesia or jet lag.
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Paragraph 0510; 0511
(2019/10/19)
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- Identification of human T2R receptors that respond to bitter compounds that elicit the bitter taste in compositions, and the use thereof in assays to identify compounds that inhibit (block) bitter taste in compositions and use thereof
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The present invention relates to the discovery that specific human taste receptors in the T2R taste receptor family respond to particular bitter compounds present in, e.g., coffee. Also, the invention relates to the discovery of specific compounds and compositions containing that function as bitter taste blockers and the use thereof as bitter taste blockers or flavor modulators in, e.g., coffee and coffee flavored foods, beverages and medicaments. Also, the present invention relates to the discovery of a compound that antagonizes numerous different human T2Rs and the use thereof in assays and as a bitter taste blocker in compositions for ingestion by humans and animals.
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Page/Page column 303
(2016/02/26)
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- BITTER TASTE MODIFIERS INCLUDING SUBSTITUTED 1-BENZYL-3-(1-(ISOXAZOL-4-YLMETHYL)-1H-PYRAZOL-4-YL)IMIDAZOLIDINE-2,4-DIONES AND COMPOSITIONS THEREOF
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The present invention includes compounds and compositions known to modify the perception of bitter taste, and combinations of said compositions and compounds with additional compositions, compounds, and products. Exemplary compositions comprise one or more of the following: cooling agents; inactive drug ingredients; active pharmaceutical ingredients; food additives or foodstuffs; flavorants, or flavor enhancers; food or beverage products; bitter compounds; sweeteners; bitterants; sour flavorants; salty flavorants; umami flavorants; plant or animal products; compounds known to be used in pet care products; compounds known to be used in personal care products; compounds known to be used in home products; pharmaceutical preparations; topical preparations; cannabis-derived or cannabis-related products; compounds known to be used in oral care products; beverages; scents, perfumes, or odorants; compounds known to be used in consumer products; silicone compounds; abrasives; surfactants; warming agents; smoking articles; fats, oils, or emulsions; and/or probiotic bacteria or supplements.
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Paragraph 0469; 0470
(2017/01/19)
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- FUSED PYRIMIDINE DERIVATIVES HAVING INHIBITORY ACTIVITY ON FMS KINASES
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Disclosed are a fused pyrimidine derivative of formula (I), and a pharmaceutically acceptable salt, stereoisomer, hydrate and solvate thereof, which have an excellent inhibitory activity on FMS kinases, and a pharmaceutical composition comprising the same is effective in preventing or treating diseases caused by abnormal activation of FMS kinases such as immunologic diseases, metabolic diseases, inflammatory diseases, cancers and tumors.
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- IMIDAZOTRIAZINONE COMPOUNDS
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The present invention provides imidazotriazinone compounds which are inhibitors of phosphodiesterase 9 and pharmaceutically acceptable salt thereof. The present invention further provides processes, pharmaceutical compositions, pharmaceutical preparations and pharmaceutical use of the compounds in the treatment of PDE9 associated diseases or disorders in mammals, including humans.
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Paragraph 0527; 0528
(2013/10/08)
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- IMIDAZOTRIAZINONE COMPOUNDS
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The present invention provides imidazotriazinone compounds which are inhibitors of phosphodiesterase 9. The present invention further provides processes, pharmaceutical compositions, pharmaceutical preparations and pharmaceutical use of the compounds in the treatment of PDE9 associated diseases or disorders in mammals, including CNS or neurodegeneration disorder.
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Page/Page column 87
(2012/04/10)
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- SUBSTITUTED N-(1H-INDAZOL-4-YL)IMIDAZO[1,2-a]PYRIDINE-3-CARBOXAMIDE COMPOUNDS AS TYPE III RECEPTOR TYROSINE KINASE INHIBITORS
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Compounds of Formula I: and pharmaceutically acceptable salts thereof in which R1, R2, R3, R4, R5 and R6 have the meanings given in the specification, are inhibitors of cFMS and are useful in the treatment of fibrosis, bone-related diseases, cancer, autoimmune disorders, inflammatory diseases, cardiovascular diseases, pain and burns in a mammal
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Page/Page column 133
(2012/06/30)
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- SULFONYLPIPERAZINE DERIVATIVES THAT INTERACT WITH GLUCOKINASE REGULATORY PROTEIN FOR THE TREATMENT OF DIABETES
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The present invention relates to compounds of Formula I, or pharmaceutically acceptable salts thereof, that interact with glucokinase regulatory protein. In addition, the present invention relates to methods of treating type 2 diabetes, and other diseases and/or conditions where glucokinase regulatory protein is involved using the compounds, or pharmaceutically acceptable salts thereof, and pharmaceutical compositions that contain the compounds, or pharmaceutically acceptable salts thereof.
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Page/Page column 577
(2012/03/26)
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- SUBSTITUTED N-(1H-INDAZOL-4-YL)IMIDAZO[1, 2-A]PYRIDINE-3- CARBOXAMIDE COMPOUNDS AS CFMS INHIBITORS
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Compounds of Formula (I): and pharmaceutically acceptable salts thereof in which R1, R2, R3, R4 and R5 have the meanings given in the specification, are inhibitors of cFMS and are useful in the treatment of bone-related diseases, cancer, autoimmune disorders, inflammatory diseases, cardiovascular diseases and pain.
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- PYRIDYL OXAZOLIDINONE CETP INHIBITOR
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The compound of Formula I, including pharmaceutically acceptable salts, is a CETP inhibitor, and is useful for raising HDL-cholesterol, reducing LDL-cholesterol, and for treating or preventing atherosclerosis. In the compound of Formula 1, R is H or Csub
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Page/Page column 20-21
(2011/04/14)
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- Identification of human T2R receptors that respond to bitter compounds that elicit the bitter taste in compositions, and the use thereof in assays to identify compounds that inhibit (block) bitter taste in composition and use thereof
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The present invention relates to the discovery that specific human taste receptors in the T2R taste receptor family respond to particular bitter compounds present in, e.g., coffee. Also, the invention relates to the discovery of specific compounds and compositions containing that function as bitter taste blockers and the use thereof as bitter taste blockers or flavor modulators in, e.g., coffee and coffee flavored foods, beverages and medicaments. Also, the present invention relates to the discovery of a compound that antagonizes numerous different human T2Rs and the use thereof in assays and as a bitter taste blocker in compositions for ingestion by humans and animals.
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- Substituted 1,2,4-triazolo[3,4-a]phthalazine derivatives as GABA alpha 5 ligands
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Substituted 1,2,4-Triazolo[3,4-A]phthalazine derivatives are GABA Alpha 5 ligands and are represented by the formula
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- TRIAZOLOPYRIDINES. PART 8. NUCLEOPHILIC SUBSTITUTION REACTIONS OF 5-BROMOTRIAZOLOISOQUINOLINE AND 7-BROMO-TRIAZOLOPYRIDINE
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Nucleophilic substitution of 5-bromotriazoloisoquinoline (3) and of 7-bromo-3-methyltriazolopyridine (6) proceeds readily to give a range of 5-substituted triazoloisoquinolines (4a)-(4e), and of 7-substituted triazolopyridines (7a)-(7h) respectively.Triazoloisoquinolines have been converted into 1,3-disubstituted isoquinolines (11)-(13), (15), and (16), and triazolopyridines into 2,6-disubstituted pyridines (17)-(19).Of secondary amine nucleophiles, only piperidine reacted with 7-bromo-3-methyl-triazolopyridine (6) to give the 7-substituted derivative (7g).A second product in this reaction was a 2,6-disubstituted pyridine (8); the similar compounds (20)-(24) were the only products when morpholine or N-acetyl-piperazine were used.The reaction between 7-bromotriazolopyridine (9) and piperidine or morpholine gave in high yield the 2,6-disubstituted pyridines (25) and (26).
- Abarca, Belen,Mojarred, Fatemeh,Jones, Gurnos,Phillips, Caroline,NG, Nadine,Wastling, Jonathan
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p. 3005 - 3014
(2007/10/02)
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- NUCLEOPHILIC SUBSTITUTIONS ON BROMOTRIAZOLOPYRIDINES - AN IMPROVED ROUTE TO 2,6-DISUBSTITUTED PYRIDINES AND TO 1,3-DISUBSTITUTED ISOQUINOLINES
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A regiospecific synthesis of 2,6-disubstituted pyridines and of 1,3-disubstituted isoquinolines is described.
- Abarca, Belen,Ballesteros, Rafael,Jones, Gurnos,Mojarrad, Fatemeh
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p. 3543 - 3546
(2007/10/02)
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