- CONDENSED AZACYCLES AS SIGMA LIGAND COMPOUNDS AND USES THEREOF
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The present disclosure relates to compounds of Formula (I) and their prodrugs, solvates, pharmaceutically acceptable salts, pharmaceutical compositions, methods of use, and methods of their preparation. The compounds disclosed herein are useful for modulating Sigma receptors and have antiviral activity, and may also be useful in the treatment and/or prevention of pain disorders, neurological disorders (e.g., Parkinson's disease and Alzheimer's disease), and cancer.
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Paragraph 0395
(2022/02/22)
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- PROCESS FOR PREPARING 3-HYDROXY-3-METHYLBUTYRATE (HMB) AND SALTS THEREOF
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The present invention pertains to a process for preparing 3-hydroxy-3-methylbutyrate (HMB) or a salt thereof, the method comprising (a) reacting isobutylene oxide with cyanide in order to obtain 3- hydroxy-3-methylbutyronitrile, and (b) hydrolyzing the 3-hydroxy-3-methylbutyronitrile obtained in step (a) in order to obtain HMB, wherein hydrolysis step (b) is performed using either at least one nitrilase enzyme or, alternatively, using a combination of enzymes, said combination comprising at least one nitrile hydratase and at least one amidase.
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Page/Page column 8
(2020/10/31)
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- DEUTERATED BENZIMIDAZOLE COMPOUND AND MEDICAL USE THEREOF
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The present invention relates to a medicament for treating or preventing a disease involving Na channel, for example, neuropathic pain, nociceptive pain, inflammatory pain, small-fiber neuropathy, erythromelalgia, paroxysmal extreme pain disorder, dysuria, or multiple sclerosis, comprising a compound of formula (I) wherein R1a, R1b, R1c, and R1d are hydrogen, halogen, cyano, C1-4 alkyl, C1-4 alkoxy, etc., provided that at least one of R1a, R1b, R1c and R1d is the above C6-10 aryl, C6-10 aryloxy, etc., R2 and R3 are hydrogen, C1-6 alkyl, C3-10 cycloalkyl, etc., R4 is hydrogen, C1-6 alkyl, C3-7 cycloalkyl, etc., m is 0, 1, or 2, L is CR7R8, R7 and R8 are hydrogen, hydroxy group, C1-4 alkyl, C1-4 alkoxy, etc., or a pharmaceutically acceptable salt thereof.
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Paragraph 0271-0272
(2020/02/10)
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- Ruthenium-catalyzed formation of pyrazoles or 3-hydroxynitriles from propargyl alcohols and hydrazines
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Functionalized pyrazoles are generated from secondary propragyl alcohols and hydrazines in a ruthenium-catalyzed cascade process, consisting of redox isomerization, Michael addition, cyclocondensation and dehydrogenation steps. The same bifunctional catalyst mediates the conversion of tertiary propargyl alcohols with hydrazine to 3-hydroxynitriles via anti-Markovnikov hydroamination followed by elimination of ammonia.
- Kaufmann, Julia,J?ckel, Elisabeth,Haak, Edgar
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supporting information
p. 91 - 101
(2019/07/09)
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- BENZIMIDAZOLONE DERIVATIVES
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This invention relates to compounds and methods for the treatment of a condition mediated by CB1 receptor activity in a mammalian subject including a human, which comprises administering to a mammal in need of such treatment a therapeutically effective am
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Page/Page column 58
(2009/12/23)
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- BENZIMIDAZOLONE DERIVATIVES AS CB2 RECEPTOR LIGANDS
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This invention relates to compounds of the formula (I): or pharmaceutically acceptable salts thereof, wherein: A, B, R1, R2 and R3 are each as described herein, and compositions containing such compounds and the use of suc
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Page/Page column 71
(2008/06/13)
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- 3-methoxybenzyl thiourea derivatives and improved lipid compositions containing same
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1-(3-methoxybenzyl)-3-substituted thiourea antioxidant compounds and improved lipids compositions which are supplemented with amounts of such antioxidant compounds effective for augmenting oxidative stability of the base lipid are provided. Also provided are methods for enhancing the oxidative stability of a lipid comprising supplementing a base lipid in need of enhanced oxidative stability with at least one 1-(3-methoxybenzyl)-3-substituted thiourea compound of the present invention.
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- Elimination kinetics of β-hydroxynitriles in the gas phase
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The gas-phase elimination kinetics of primary, secondary and tertiary β-hydroxynitriles were examined in static seasoned vessels over the temperature range 360-450 °C and pressure range 47-167 Torr (1 Torr = 133.3 Pa). These reactions are homogeneous, unimolecular and follow a first-order rate law. The rate coefficients are given by the Arrhenius equation: for 3-hydroxypropionitrile log k1 = (14.29 ± 0.47) - (234.9 ± 6.3) kJ mol-1 (2.303 RT)-1; for 3-hydroxybutyronitrile log k1 = (13.76 ± 0.10) - (222.6 ± 0.7) kJ mol-1 (2.303RT)-1; and for 3-hydroxy-3-methylbutyronitrile log k1 (s-1) = (13.68 ± 0.68) - (212.5 ± 8.7) kJ mol-1 (2.303RT)-1. The decomposition rates of the β-hydroxynitriles increase from primary to tertiary carbon containing the OH group. The rates for the β-hydroxynitriles are found to be slower than those for the corresponding β-hydroxyacetylene analogs. The value of log A from 13.7 to 14.4 and the small positive ΔS≠ indicate a mechanism different from a six-centered cyclic transition state. These data appear to indicate that a four-membered cyclic transition state or a quasi-heterolytic mechanism is conceivable. Copyright
- Chuchani, Gabriel,Dominguez, Rosa M.,Rotinov, Alexandra,Quijano, Jairo,Valencia, Cristina,Vicente, Bernardo,Franco, Dimas
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- P(RNCH2CH2)3N-Catalyzed synthesis of β-hydroxy nitriles
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We herein report the successful synthesis of β-hydroxy nitriles in very good to excellent yields from aldehydes and ketones in a simple reaction that is promoted by strong nonionic bases of the title type. The reaction occurs in the presence of magnesium salts which activate the carbonyl group and stabilizes the enolate thus produced.
- Kisanga, Philip,McLeod, Dale,D'Sa, Bosco,Verkade, John
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p. 3090 - 3094
(2007/10/03)
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- Studies on steric and electronic control of 2'-3' phosphoryl migration in 2'-phosphorylated uridine derivatives and its application to the synthesis of 2'-phosphorylated oligouridylates
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For the synthesis of 2'-phosphorylated oligouridylates by use of new phosphoramidite building units, several masked phosphoryl groups have been examined as 2'-phosphate precursors, which should not be migrated to the 3' position when the 3' hydroxy protecting group must be removed to introduce a phosphoramidite residue into the 3'-position. As a consequence, bis(2-cyano-1,1-dimethylethoxy)thiophosphoryl (BCMETP) was found to be the most suitable 2'-phosphate precursor. This thiophosphoryl group could be introduced into the 2'-hydroxyl of 3',5'-silylated uridine derivative 7 by phosphitylation with bis(2-cyano-1,1-dimethylethoxy)(diethylamino)phosphine followed by sulfurization. Treatment of the 2'-thiophosphorylated product 15 with (HF)(x)·Py in THF gave exclusively the 3',5'-unprotected uridine derivative 16a. Compound 16a was converted to the phosphoramidite unit 22 via a two-step reaction. This building block was used for the solution phase synthesis of U(2'-p)pU (29) and U(2'-ps)pU (30). Both the 2-cyano-1,1-dimethylethyl and 2-cyanoethyl groups were effectively removed from the fully protected derivative 25 by treatment with DBU in the presence of N,O-bis(trimethylsilyl)acetamide (BSA). The resulting 2'-thiophosphoryl group was successfully converted to a phosphoryl group by iodine treatment to give U(2'-p)pU (29). U(2'-ps)pU (30) was also synthesized by a modified procedure without the iodine treatment. Reaction of 29 with a new biotinylating reagent in aqueous solution in the presence of MgCl2 gave a biotin-labeled product 35 having a pyrophosphate bridge at the 2' position. Reaction of 30 with monobromobimane gave the 2'-S-alkylated product 33 in aqueous solution. Application of the phosphoramidite unit 22 to the solid phase synthesis using aminopropyl CPG gel gave successfully [U(2'-p)p](n)U (n = 1, 3, 5). It was found that stability of the succinate linker between the CPG and oligouridylates was unaffected by the treatment with DBU when BSA was present. Several enzymatic properties of the synthetic 2'-phosphorylated and 2'-thiophosphorylated oligouridylates are also described.
- Sekine,Tsuruoka,Iimura,Kusuoku,Wada,Furusawa
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p. 4087 - 4100
(2007/10/03)
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- Ring Opening of Epoxides with Acetone Cyanohydrin Catalyzed by Lanthanoid(III) Alkoxides
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Ring opening of epoxide and aziridine with acetone cyanohydrin is promoted by a catalytic amount of lanthanoid(III) alkoxide to provide β-hydroxy nitrile and β-amino nitrile, respectively.
- Ohno, Hiroshi,Mori, Atsunori,Inoue, Shohei
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p. 975 - 978
(2007/10/02)
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