1611481-16-3

Upstream product

• 3398-22-9 trans-4-hydroxyproline 
• 114676-59-4 (2R,4R)-4-hydroxy-2-methoxycarbonylpyrrolidine hydrochloride 
• 77449-94-6 (2R,4R)-4-hydroxypyrrolidine-2-carboxylic acid hydrochloride 
• 51-35-4 4R-4-hydroxyproline 
• 114676-53-8 (2R,4R)-methyl 1-benzyl-4-hydroxypyrrolidine-2-carboxylate 
• 114676-54-9 (2R,4R)-1-benzyl-2-carbomethoxy-4-<(methylsulfonyl)oxy>pyrrolidine 
• 178962-09-9 methyl (2R,4S)-4-hydroxypyrrolidine-2-carboxylate 

Downstream Products

• 1611488-11-9 (R)-N-(5,5-difluoropiperidin-3-yl)benzamide 
• 627101-16-0 (2R,4R)-(4-amino-1-benzylpyrrolidin-2-yl)methanol 
• 1611481-18-5 tert-butyl (3R,5R)-1-benzyl-5-(hydroxymethyl)pyrrolidin-3-ylcarbamate 
• 1611481-20-9 tert-butyl ((3S,5R)-1-benzyl-5-hydroxypiperidin-3-yl)carbamate 
• 1611481-21-0 tert-butyl (3R,5S)-5-hydroxypiperidin-3-ylcarbamate 
• 1611481-26-5 (R)-(5-amino-3,3-difluoropiperidin-1-yl)(phenyl)methanone 

Relevant academic research and scientific papers

A sub-milligram-synthesis protocol for in vitro screening of HDAC11 inhibitors

This work demonstrated the high efficiency of a sub-milligram-synthesis based medicinal chemistry method. Totally 72 compounds, consisting a tri-substituted pyrrolidine core, were prepared. Around 0.1 mg of each compound was solid-phase synthesized. Based on the additive property of UV absorptions of unconjugated chromophores of a molecule, these compounds were quantified by UV measurement. A hit, whose IC50 value was 1.2 μM in HDAC11 inhibition assays, highlights the applicability of the approach reported here in future optimization works.

Enantioselective synthesis and physicochemical properties of libraries of 3-amino- and 3-amidofluoropiperidines

The enantioselective syntheses of 3-amino-5-fluoropiperidines and 3-amino-5,5-difluoropiperidines were developed using the ring enlargement of prolinols to access libraries of 3-amino- and 3-amidofluoropiperidines. The study of the physicochemical properties revealed that fluorine atom(s) decrease(s) the pKa and modulate(s) the lipophilicity of 3-aminopiperidines. The relative stereochemistry of the fluorine atoms with the amino groups at C3 on the piperidine core has a small effect on the pK a due to conformationnal modifications induced by fluorine atom(s). In the protonated forms, the C-F bond is in an axial position due to a dipole-dipole interaction between the N-H+ and C-F bonds. Predictions of the physicochemical properties using common software appeared to be limited to determine correct values of pKa and/or differences of pK a between cis- and trans-3-amino-5-fluoropiperidines.