- Stereoselective inhibition of serotonin re-uptake and phosphodiesterase by dual inhibitors as potential agents for depression
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Multi-target compounds where more than one functional activity is incorporated into the same molecule may have advantages in treating disease states. Selective serotonin re-uptake inhibitors (SSRIs)a (i.e., (R)- and (S)-norfluoxetine) were chemically linked to a PDE4 inhibitor via a five carbon bridge. The new dual PDE4 inhibitor/SSRIs (i.e., (R)-8 and (S)-8) showed moderately potent but highly selective serotonin re-uptake inhibition (IC50 values of 173 and 42 nM, respectively) in vitro. The dual PDE4 inhibitor/SSRIs (R)-8 and (S)-8 also inhibited PDE4D2 (i.e., Ki values of 106 and 253 nM, respectively). Due to the synergistic functional activity, PDE4 inhibitor/SSRIs may be effective in treating diseases such as depression.
- Cashman, John R.,Voelker, Troy,Johnson, Robert,Janowsky, Aaron
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p. 337 - 343
(2011/03/17)
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- TREATMENT OF METABOLIC SYNDROME WITH NOVEL AMIDES
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The present invention relates to the treatment of metabolic syndrome or disorders associated with metabolic syndrome comprising administering a compound of the invention.
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Page/Page column 83-85
(2009/07/17)
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- MODULATORS OF CENTRAL NERVOUS SYSTEM NEUROTRANSMITTERS
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Disclosed are agents having pharmacological activity against cellular receptors and intracellular singaling, particularly receptors and sigaling pathways of central nervous system (CNS) neurotransmitters. Also disclosed are related methods and compositions for the treatment or prevention of diseases or disorders using the agents.
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Page/Page column 148-149
(2010/10/20)
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- Asymmetric dihydroxylation route to (R)-isoprenaline, (R)-norfluoxetine and (R)-fluoxetine
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An efficient asymmetric synthesis of enantiomerically pure (R)-isoprenaline, (R)-norfluoxetine and (R)-fluoxetine is described using Sharpless asymmetric dihydroxylation as the key step.
- Kumar, Pradeep,Upadhyay, Rajesh Kumar,Pandey, Rajesh Kumar
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p. 3955 - 3959
(2007/10/03)
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- Chemoenzymatic synthesis2 of both enantiomers of fluoxetine, tomoxetine and nisoxetine: Lipase-catalyzed resolution of 3-aryl-3-hydroxypropanenitriles
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A facile preparation of (±)-3-hydroxy-3-phenylpropanenitrile has been carried out by ring-opening of styrene oxide with NaCN in aqueous ethanol. Subsequent kinetic resolution of this material via lipase-mediated transesterification gave the S-alcohol and R-acetate in excellent yields and high enantioselectivities, particularly with lipase PS-C 'Amano' II. The effect of solvents and immobilization of the lipase has also been investigated. It is interesting to note that the use of immobilized lipase for this transesterification process in hydrophobic solvents (diisopropyl ether, toluene and hexane) enhanced the reaction rate drastically and gave optimal yields with high enantioselectivity (>99%). Moreover, enantiopure 3-hydroxy-3-phenylpropanenitrile products have been converted via enantioconvergent routes into the (R)- and (S)-enantiomers of the important anti-depressants fluoxetine, tomoxetine, nisoxetine and norfluoxetine.
- Kamal, Ahmed,Khanna,Ramu
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p. 2039 - 2051
(2007/10/03)
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- An asymmetric dihydroxylation route to enantiomerically pure norfluoxetine and fluoxetine
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An efficient, practical asymmetric synthesis of (R)-norfluoxetine 1 and (R)-fluoxetine 2 has been achieved. The synthetic strategy features a Sharpless asymmetric dihydroxylation (SAD) route to the common building block 1,3-amino alcohol 9, from which (R)-norfluoxetine, (R)-fluoxetine and other related analogs can be synthesized.
- Pandey, Rajesh Kumar,Fernandes, Rodney A.,Kumar, Pradeep
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p. 4425 - 4426
(2007/10/03)
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