858130-53-7Relevant articles and documents
AMINOPROPOXYPIPERIDINYLAMIDO DERIVATIVES HAVING MULTIMODAL ACTIVITY AGAINST PAIN
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, (2019/08/26)
The present invention relates to aminopropoxyphenylpiperidinylamidoderivatives having dual pharmacological activity towards both the α2δ subunit, in particular the α2δ-1 subunit, of the voltage-gated calcium channel and the μ-opioid receptor, to processes of preparation of such compounds, to pharmaceutical compositions comprising them, and to their use in therapy, in particular for the treatment of pain.
AMINOPROPOXYPHENYL AND BENZYL 1-OXA-4,9-DIAZASPIROUNDECANE DERIVATIVES HAVING MULTIMODAL ACTIVITY AGAINST PAIN
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, (2019/10/15)
The present invention relates to aminopropoxyphenyl and benzyl 1-oxa-4,9- diazaspiroundecanederivatives having dual pharmacological activity towards both the α2δ subunit, in particular the α2δ-1 subunit, of the voltage-gated calcium channel and the μ-opioid receptor, to processes of preparation of such compounds, to pharmaceutical compositions comprising them, and to their use in therapy, in particular for the treatment of pain.
A chemoenzymatic dynamic kinetic resolution approach to enantiomerically pure (R)- and (S)-duloxetine
Traeff, Annika,Lihammar, Richard,Baeckvall, Jan-E.
, p. 3917 - 3921 (2011/07/08)
The synthesis of (R)-duloxetine is described. Dynamic kinetic resolution of β-hydroxynitrile rac-1 using Candida antarctica lipase B (CALB, N435) and ruthenium catalyst 6 afforded β-cyano acetate (R)-2 in high yield and in excellent enantioselectivity (98% ee). The subsequent synthetic steps were straightforward and (R)-duloxetine was isolated in 37% overall yield over 6 steps. The synthetic route also constitute a formal total synthesis of (S)-duloxetine.
Inhibition of serotonin and norepinephrine reuptake and inhibition of phosphodiesterase by multi-target inhibitors as potential agents for depression
Cashman, John R.,Ghirmai, Senait
experimental part, p. 6890 - 6897 (2010/01/06)
Compounds possessing more than one functional activity incorporated into the same molecule may have advantages in treating complex disease states. Balanced serotonin/norepinephrine reuptake inhibitors (SNRIs) (i.e., (R)- and (S)-norduloxetine) were chemically linked to a PDE4 inhibitor via a five carbon bridge. The new dual SNRI/PDE4 inhibitors (i.e., (R)-15 and (S)-15) showed moderately potent serotonin reuptake inhibition (IC50 values of 442 and 404 nM, respectively) but low reuptake inhibition of norepinephrine (IC50 values of 2097 and 2190 nM, respectively) in vitro. The dual SNRI/PDE4 inhibitors (i.e., (R)-15 and (S)-15) also inhibited PDE4D2 (i.e., Ki values of 23 and 45 nM, respectively). Due to their synergistic functional activity, SNRI/PDE4 inhibitors may be effective in treating diseases such as depression.
Polymer-supported chiral sulfonamide catalyzed one-pot reduction of β-keto nitriles: A practical synthesis of (R)-fluoxetine and (R)-duloxetine
Wang, Guangyin,Liu, Xingshun,Zhao, Gang
, p. 1873 - 1879 (2007/10/03)
Enantioselective reduction of β-keto nitriles to optically active 1,3-amino alcohols has been carried out in one step using an excess of borane-dimethyl sulfide complex as a reductant and a polymer-supported chiral sulfonamide as a catalyst with moderate to high enantioselectivity. The facile and enantioselective method to prepare optically active 1,3-amino alcohols to be converted into 3-aryloxy-3-arylpropylamine-type antidepressant drugs (R)-fluoxetine, and (R)-duloxetine is also reported.
Chemoenzymatic synthesis of duloxetine and its enantiomer: Lipase-catalyzed resolution of 3-hydroxy-3-(2-thienyl) propanenitrile
Kamal, Ahmed,Khanna, G. B. Ramesh,Ramu,Krishnaji
, p. 4783 - 4787 (2007/10/03)
An efficient and facile chemoenzymatic synthesis of duloxetine by lipase mediated resolution of 3-hydroxy-3-(2-thienyl)propanenitrile has been achieved. This process also describes an enantioconvergent synthesis of duloxetine via a Mitsunobu reaction.
