620606-74-8

Upstream product

• 942302-88-7 2-[3-(3-fluorobenzyloxy)phenyl]ethylamine 
• 50-00-0 formaldehyd 
• 926202-82-6 2-(4-(3-fluorobenzyloxy)phenyl)ethanamine 
• 456-41-7 1-(Bromomethyl)-3-fluorobenzene 
• 13398-94-2 2-(3-hydroxyphenyl)ethanol 
• 954502-56-8 2-{2-[3-(3-fluorobenzyloxy)phenyl]ethyl}isoindole-1,3-dione 
• 954502-55-7 2-[3-(3-fluorobenzyloxy)phenyl]ethanol 

Relevant academic research and scientific papers

S1P RECEPTORS MODULATORS

The invention relates to novel compounds that have S1P receptor modulating activity and, preferably, apoptotic activity and/or anti proliferative activity against cancer cells and other cell types. Further, the invention relates to a pharmaceutical comprising at least one compound of the invention for the treatment of diseases and/or conditions caused by or associated with inappropriate S1P receptor modulating activity or expression, for example, cancer. A further aspect of the invention relates to the use of a pharmaceutical comprising at least one compound of the invention for the manufacture of a medicament for the treatment of diseases and/or conditions caused by or associated with inappropriate S1P receptor modulating activity or expression such as cancer.

Solid-phase synthesis and insights into structure-activity relationships of safinamide analogues as potent and selective inhibitors of type B monoamine oxidase

Safinamide, (S)-N2-{4-[(3-fluorobenzyl)oxy]benzyl}alaninamide methanesulfonate, which is in phase III clinical trials as an anti-Parkinson drug, and a library of alkanamidic analogues were prepared through an expeditious solid-phase synthesis and evaluated for their monoamine oxidase B (MAO-B) and monoamine oxidase A (MAO-A) inhibitory activity and selectivity. (S)-3-Chlorobenzyloxyalaninamide (8) and (S)-3-chlorobenzyloxyserinamide (13) derivatives proved to be more potent MAO-B inhibitors than safinamide (IC 50 = 33 and 43 nM, respectively, vs 98 nM) but with a lower MAO-B selectivity (SI = 3455 and 1967, respectively, vs 5918). The highest MAO-B inhibitory potency (IC50 = 17 nM) and a good selectivity (SI = 2941) were displayed by (R)-21, a tetrahydroisoquinoline analogue of safinamide. Structure-affinity relationships and docking simulations pointed out strong negative steric effects of α-aminoamide side chains and para substituents of the benzyloxy groups and favorable hydrophobic interactions of meta substituents. The significantly diverse MAO-B affinities of a number of R and S α-aminoamide enantiomers, including the two rigid analogues (21) of safinamide, indicated likely enantioselective interactions at the enzymatic binding sites.

Isoquinoline derivatives

Disclosed are isoquinolino derivatives of the formula wherein Y is >C═O or —CH2—, Z is >C═O or —CH2—, and R1, R2 and m are as defined herein as well as the pharmaceutically acceptable salts thereof. These compounds are MAO-B selective inhibitors useful, inter alia, in the treatment of Alzheimer's disease and/or senile dementia.