130194-43-3Relevant articles and documents
Stereoselective inhibition of serotonin re-uptake and phosphodiesterase by dual inhibitors as potential agents for depression
Cashman, John R.,Voelker, Troy,Johnson, Robert,Janowsky, Aaron
, p. 337 - 343 (2011/03/17)
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.
MODULATORS OF CENTRAL NERVOUS SYSTEM NEUROTRANSMITTERS
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Page/Page column 148-149, (2010/10/20)
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.
Chemoenzymatic synthesis2 of both enantiomers of fluoxetine, tomoxetine and nisoxetine: Lipase-catalyzed resolution of 3-aryl-3-hydroxypropanenitriles
Kamal, Ahmed,Khanna,Ramu
, p. 2039 - 2051 (2007/10/03)
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.