- Synthesis and in vitro affinities of various MDL 100907 derivatives as potential 18F-radioligands for 5-HT2A receptor imaging with PET
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Radiolabelled piperidine derivatives such as [11C]MDL 100907 and [18F]altanserin have played an important role in diagnosing malfunction in the serotonergic neurotransmission. A variety of novel piperidine MDL 100907 derivatives, possible to label with 18F-fluorine, were synthesized to improve molecular imaging properties of [11C]MDL 100907. Their in vitro affinities to a broad spectrum of neuroreceptors and their lipophilicities were determined and compared to the clinically used reference compounds MDL 100907 and altanserin. The novel compounds MA-1 (53) and (R)-MH.MZ (56) show Ki-values in the nanomolar range towards the 5-HT2A receptor and insignificant binding to other 5-HT receptor subtypes or receptors. Interestingly, compounds MA-1 (53), MH.MZ (55) and (R)-MH.MZ (56) provide a receptor selectivity profile similar to MDL 100907. These compounds could possibly be preferable antagonistic 18F-tracers for visualization of the 5-HT2A receptor status. Medium affine compounds (VK-1 (32), (51), (52), (54)) were synthesized and have Ki values between 30 and 120 nM. All promising compounds show log P values between 2 and 3, that is, within the range of those for the established radiotracers altanserin and MDL 100907. The novel compounds MA-1 (53) and (R)-MH.MZ (56) thus appear to be promising high affine and selective tracers of 18F-labelled analogues for 5-HT2A imaging with PET.
- Herth, Matthias M.,Kramer, Vasko,Piel, Markus,Palner, Mikael,Riss, Patrick J.,Knudsen, Gitte M.,Roesch, Frank
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experimental part
p. 2989 - 3002
(2009/09/05)
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- COMBINATION OF A HYPNOTIC AGENT AND R (+)-ALPHA-(2,3-DIMETHOXY-PHENYL)-1-[2-(4-FLUOROPHENYL)ETHYL]-4-PIPERIDINEMETHANOL AND THERAPEUTIC APPLICATION THEREOF
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The invention concerns the combination of a short-acting hypnotic agent and R-(+)-α-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol (Compound A) or its prodrug having the Formula II: wherein R is C1-C20 alkyl o
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Page/Page column 10
(2008/12/06)
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- Processes for the preparation of (R)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol"
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The present invention provides various processes for the preparation of (R)-±-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol. These processes may be characterized by the following scheme:
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Page/Page column 18; 66
(2010/11/25)
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- Use of MDL-100,907 for treatment of allergic and eosinophil mediated diseases
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Methods of modulating eosinophil migration, chemotaxis or generation, in vitro, ex vivo, and in vivo are provided. Methods include contacting eosinophils with an amount of 5-HT2A receptor agonist or antagonist sufficient to modulate eosinophil migration, chemotaxis or generation.
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Page/Page column 10; 11
(2010/10/20)
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- The "reverse-tethered" ruthenium (II) catalyst for asymmetric transfer hydrogenation: Further applications
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The attachment of a tethering group from the basic nitrogen atom to the arene ligand of a ruthenium(II) catalyst greatly improves its ability to catalyze asymmetric transfer hydrogenation (ATH) reactions. In this paper, we describe further applications of this versatile system to an extended substrate range.
- Morris, David J.,Hayes, Aidan M.,Wills, Martin
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p. 7035 - 7044
(2007/10/03)
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- Novel processes for the preparation of (R)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol
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The present invention provides various processes for the preparation of (R)-α-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol. These processes may be characterized by the following scheme:
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- Novel processes for the preparation or (R)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol
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The present invention provides various processes for the preparation of (R)-α-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol. These processes may be characterized by the following scheme:
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- Use of (+)-a-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl) ethyl]-4-piperidinemethanol or its prodrug in the treatment of symptoms of dementia and dopamine induced psychosis
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The present invention is directed to use of (+)-α-(2,3-Dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol or its prodrug (Formula II) in treating patients for symptoms of dementia and dopamine induced psychosis.
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- USE OF R-(+)-alpha-(2,3-DIMETHOXYPHENYL-1-[2-(4-FLUOROPHENYL) ETHYLl-4-PIPERIDINEMETHANOL FOR THE TREATMENT OF SLEEP DISORDERS
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A method of treating a patient for a Sleep Disorder comprising administering an effective amount of R-(+)-α-(2,3-Dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol or a pharmaceutically acceptable salt thereof to a patient in need of such treatment.
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- Use of (+)- alpha -(2,3-dimethoxyphenyl-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol in treating depressive disorders and bipolar disorders
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The present invention is directed to the use of (+)- alpha -(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol in treating Depressive Disorders and Bipolar Disorders.
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- Esters of (+)- alpha -(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl) ethyl]-4-piperidinemethanol
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The present invention is directed to esters of (+)- alpha -(2,3 Dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol, pharmaceutical formulations, methods of making and methods of using these esters. These compounds antagonize the effects of serotonin at the 5HT2A receptor and are useful in treating various conditions such as, for example, psychoses such as schizophrenia.
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- An efficient synthesis of the precursors of [11C]MDL 100907 labeled in two specific positions
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An efficient, integrated route for the synthesis of two precursors of [11C]MDL 100907 labeled in the 2'- or 3'-methoxy position is reported. The synthesis involved a one-pot, two-step process to transform the intermediate esters to ketones and subsequent resolution of the racemic alcohols to their respective enantiomers. The resolved, enantiomerically pure phenol precursors were reacted with high specific activity [11C]methyl iodide to produce [11C]MDL 100907 labeled in two specific positions.
- Huang, Yiyun,Mahmood, Khalid,Mathis, Chester A.
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p. 949 - 957
(2007/10/03)
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- Treatment of obsessive-compulsive disorders with 5-HT2 antagonists
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The present invention is directed to 5-HT2 antagonists and their use as agents in the treatment of obsessive-compulsive disorders (OCD). The invention is particularly directed to the compound (+)-α-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)eth
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- Synthesis and preliminary in vivo evaluation of [11C]MDL 100907: A potent and selective radioligand for the 5-HT2A receptor system
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11C-Labeled MDL 100907 and MDL 100009 were prepared by the reaction of [11C]CH3I with the corresponding phenol precursors. In vivo studies conducted in rats and a baboon demonstrated that intravenously injected [2-O[11C]CH3]MDL 100907 was regionally distributed in the brain in a manner consistent with the known distribution of 5-HT2A receptors. Injection of [2-O[11C]CH3]MDL 100009 resulted in a uniform brain distribution of radioactivity without regional localization consistent with the lower affinity of MDL 100009 for 5-HT2A receptors.
- Mathis,Mahmood,Huang,Simpson,Gerdes,Price
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- (+)-α-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol
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The present invention is directed to a new 5HT2 antagonist, (+)-α-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol, and its use in the treatment of a number of disease states.
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