114446-51-4Relevant 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
experimental part, 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.
An efficient route to enantiomerically pure antidepressants: Tomoxetine, nisoxetine and fluoxetine
Schneider,Goergens
, p. 525 - 528 (2007/10/02)
Both enantiomers (R)- and (S)-3-chloro-1-phenyl-1-propanol can be obtained conveniently by an efficient enzymatic resolution process. They can be converted via enantioconvergent routes into all enantiomers of the important antidepressants (R)- and (S)-Tomoxetine, Fluoxetine and Nisoxetine.
Chiral Synthesis via Organoboranes. 18. Selective Reductions. 43. Diisopinocampheylchloroborane as an Excellent Chiral Reducing Reagent for the Synthesis of Halo Alcohols of High Enantiomeric Purity. A Highly Enantioselective Synthesis of Both Optical Isomers of Tomoxetine, Fluoxetine, a
Srebnik, Morris,Ramachandran, P.V.,Brown, Herbert C.
, p. 2916 - 2920 (2007/10/02)
Diisopinocampheylchloroborane, dIpc2BCl, reduces ring and chain sustituted haloaralkyl ketones to the corresponding halo alcohols in excellent enantiomeric excess.In certain cases these alcohols can be upgraded by simple methods to essentially 100percent ee.For instance, (+)- or (-)-3-chloro-1-phenyl-1-propanol is initially obtained in 97percent ee.Simple recrystallisation then furnishes the pure enantiomers.These chiral halo alcohols are highly versatile intermediates.They can be readily cyclized to oxiranes and 2-substituted tetrahydrofurans with retention of chirality.Utilizing this methodology, we have developed an efficient, highly enantioselective synthesis of both optical isomers of the antidepressant drugs, Tomoxetine, Fluoxetine, and Nisoxetine, from the common intermediates (+)-or (-)-3-chloro-1-phenyl-1-propanol.
