Properties and Exciting Facts About 5,5-Dimethyloxazolidine-2,4-dione

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Levetiracetam ((S)-alpha-ethyl-2-oxo-pyrrolidine acetamide, ucb L059) is a novel potential antiepileptic agent presently in clinical development with unknown mechanism of action. The finding that its anticonvulsant activity is highly stereoselective (Gower et al., 1992) led us to investigate the presence of specific binding sites for [3H]levetiracetam in rat central nervous system (CNS). Binding assays, performed on crude membranes, revealed the existence of a reversible, saturable and stereoselective specific binding site. Results obtained in hippocampal membranes suggest that [3H]levetiracetam labels a single class of binding sites (n(H) = 0.92 ± 0.06) with modest affinity (K(d) = 780 ± 115 nM) and with a high binding capacity (B(max) = 9.1 ± 1.2 pmol/mg protein). Similar K(d) and B(max) values were obtained in other brain regions (cortex, cerebellum and striatum). ucb L060, the (R) enantiomer of levetiracetam, displayed about 1000 times less affinity for these sites. The binding of [3H]levetiracetam is confined to the synaptic plasma membranes in the central nervous system since no specific binding was observed in a range of peripheral tissues including heart, kidneys, spleen, pancreas, adrenals, lungs and liver. The commonly used antiepileptic drugs carbamazepine, phenytoin, valproate, phenobarbital and clonazepam, as well as the convulsant agent t-butylbicyclophosphorothionate (TBPS), picrotoxin and bicuculline did not displace [3H]levetiracetam binding. However, ethosuximide (pK(i) = 3.5 ± 0.1), pentobarbital (pK(i) = 3.8 ± 0.1), pentylenetetrazole (pK(i) = 4.1 ± 0.1) and bemegride (pK(i) = 5.0 ± 0.1) competed with [3H]levetiracetam with pK(i) values comparable to active drug concentrations observed in vitro. Structurally related compounds, including piracetam and aniracetam, also displaced [3H]levetiracetam binding. (S) Stereoisomer homologues of levetiracetam demonstrated a rank order of affinity for [3H]levetiracetam binding in correlation with their anticonvulsant activity in the audiogenic mouse test (r2 = 0.84, n = 12, P< 0.0001). These results support a possible role of this binding site in the anticonvulsant activity of levetiracetam and substantiate the singular pharmacological profile of this compound. This site remains however to be further characterised. If you are interested in 695-53-4, you can contact me at any time and look forward to more communication. HPLC of Formula: C5H7NO3

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[Problem] imidazole compound or its pharmacologically acceptable salt in the melanocortin receptor activity that operates as an active ingredient of a pharmaceutical composition comprising. “I” general formula [a]” Formula, the aryl group may be substituted A ring represents a; R1 Represents a hydrogen atom, or an alkyl group which may be substituted represented; R2 Represents a hydrogen atom, a halogen atom or represents a; R3 The alkyl group may be substituted ” represented by the imidazole compound, its pharmacologically acceptable salt as an active ingredient in a pharmaceutical composition. [Drawing] no (by machine translation)

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The invention provides compounds of formula (I), wherein R1, R 2, R3, R4, R5, n and X are as defined in the specification, a process for their preparation, pharmaceutical compositions containing them, a process for preparing pharmaceutical compositions, their use in therapy and intermediates of use in their preparation.

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The total synthesis of four actinoranone stereoisomers led to unambiguous assignment of relative and absolute stereochemistry of the natural product. Key features of the convergent, fully stereocontrolled route include the use of a Negishi carbozirconation/iodination, a Friedel?Crafts cyclization, a Felkin-controlled addition reaction, a Mitsunobu reaction, and a late-stage C?H oxidation.

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An asymmetric synthesis of (-)-cytisine has been achieved. The piperidine C-ring was formed using a stereodivergent intramolecular 6-endo aza-Michael addition. The B-ring was established by intramolecular pyridine N-alkylation. The absolute stereochemistry was established by an Evans acyl oxazolidinone enolate alkylation reaction that proceeded with an unexpected stereochemical outcome due to participation of the pyridine nitrogen lone pair.

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The present invention relates to compounds of the general formula (I) having a selective FKBP51 ligand scaffold, pharmaceutically acceptable salts of these compounds and pharmaceutical compositions containing at least one of these compounds together with pharmaceutically acceptable carrier, excipient and/or diluents. Said selective FKBP51 ligand compounds can be used for prophylaxis and/or treatment of psychiatric disorders and neurodegenerative diseases, disorders and conditions.

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Compounds of Formula (I), 1 are provided where T is CHO, CON, or C(OH)R1R2; R1 and R2 are hydrogen, optionally substituted lower alkyl, CF3, optionally substituted alkenyl, or optionally substituted alkynyl; R3 is hydrogen or optionally substituted lower alkyl; R4 is (CF3)nalkyl, (CF3)n(substitutedalkyl), (CF3)nalkylphenyl, (CF3)nalkyl(substitutedphenyl), or (F)ncycloalkyl; n=1-3; R5 is hydrogen, halogen, CF3, diene fused to Y when Y=C, or substituted diene fused to Y when Y=C; W, Y and Z are C, CR6 or N where at least one of W, Y or Z are C; R6 is hydrogen, halogen, or optionally substituted lower alkyl; X is O, S, SO2, or NR7; R7 is hydrogen, optionally substituted lower alkyl, optionally substituted benzyl, or optionally substituted phenyl; and R8 is lower alkyl, CF3, or optionally substituted phenyl. Methods of preparing and using these compounds for inhibiting beta amyloid production and for treatment of Alzheimer’s Disease and Down’s syndrome are also described

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Herein, we describe the enantioselective construction of the 12-membered macrocyclic pyrrole core of marineosin A in 5.1 % overall yield from (S)-propylene oxide. The route features a key Stetter reaction to install a 1,4-diketone, which is subjected to Paal-Knorr pyrrole synthesis and ring-closing metathesis to afford the macrocycle. A divergence point in the synthetic scheme also enabled access to a highly functionalized spiroaminal model system through an acid-mediated hydroxy oxo amide cyclization strategy. Copyright

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An efficient enantioselective synthesis of cermizine D has been developed that exploits the use of a common intermediate to access over 85% of the carbon backbone. Key steps include an organocatalyzed heteroatom Michael addition, a diastereoselective alkylation with alpha-iodomethyl phenyl sulfide, a conjugate addition to a vinyl sulfone species, and a sulfone coupling/desulfurization sequence to join the two major subunits.

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(+)-Wutaienin (3) and its C-7 methyl ether (4), isolated from Zanthoxylum wutaiense, were found to be unprecedented 8,9?-neolignans containing an (S)-2-(1,1-dimethyl-1-hydroxymethyl)-7-methoxydihydrobenzofuran skeleton. Wutaienin (3) was present in the plant as an inseparable 1:1 mixture of the (7,8)-syn-diastereoisomers. The diastereoisomeric mixture was characterized by comparison with four possible diastereoisomers, which were enantioselectively synthesized from (S)-5-bromo-(1,1-dimethyl-1-hydroxymethyl)-7-methoxydihydrobenzofuran using Evans’ oxazolidinone-assisted asymmetric aldol condensation to install the chiral centers at the C-7 and C-8 positions.

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