137496-70-9

Usage

Purpose

Antidiabetic medication

Mechanism of action

Inhibits the enzyme DPP-4 (dipeptidyl peptidase-4)

Effect on blood sugar levels

Increases insulin levels and decreases glucagon levels

Administration

Orally

Approved for use

Treatment of type 2 diabetes

Precautions

Consult with a healthcare professional before use

Potential issues

Side effects and interactions with other medications

Upstream product

• 15761-39-4 1-(tert-butoxycarbonyl)-L-proline 
• 108-69-0 3,5-dimethylaminoaniline 
• 15761-39-4 N-tert-butoxycarbonyl-proline 
• 220926-85-2 N-(tert-butoxycarbonyl)-N-(3-trans-phenyl-2-propenyl)-3-chloropropylamine 
• 198218-71-2 (S)-N-(tert-butoxycarbonyl)-2-(2-phenyl)ethenylpyrrolidine 
• 116861-31-5 tert-butyl N-(3-chloropropyl)carbamate 
• 350022-46-7 N-(tert-butoxycarbonyl)-2-(2-phenylethenyl)pyrrolidine 
• 86953-79-9 tert-butyl pyrrolidine-1-carboxylate 

Downstream Products

• 1092577-93-9 C₁₇H₂₆N₂O₂S 
• 1092577-91-7 C₁₇H₂₆N₂O₂S 
• 1361321-96-1 (S)-1-(4-methoxy-benzenesulfonyl)-pyrrolidine-2-carboxylicacid (3,5-dimethyl-phenyl)-amide 
• 220037-58-1 (S)-Pyrrolidine-2-carboxylic acid (3,5-dimethyl-phenyl)-amide 

Relevant academic research and scientific papers

On-bead combinatorial approach to the design of chiral stationary phases for HPLC

A library of 36 L-amino acid anilides, which are potential selectors for chiral HPLC, was synthesized in solution and attached to functionalized macroporous polymer beads. The best selector from the library was identified by a deconvolution process using

Insights into Fast Amide Couplings in Aqueous Nanomicelles

1-Ethyl-3-(3-(dimethylamino)propyl)-carbodiimide (EDC?HCl) has both lipophilic and hydrophilic regions, causing self-aggregation (also called nanoparticle formation) in an aqueous medium containing PS-750-M amphiphile. Kinetic and proton nuclear magnetic resonance studies were used to probe the effect of different organic bases on the potential nanoparticle formation of EDC?HCl. It also reveals why the pyridine base works better under micellar conditions. The methodology was examined on the multigram scale synthesis of bioactive molecules, where excellent reaction yields were obtained without product epimerization while maintaining a shorter reaction time.

Chiral Lewis Base-Catalyzed, Enantioselective Reduction of Unprotected β-Enamino Esters with Trichlorosilane

Catalytic asymmetric reduction of N-unsubstituted β-enamino esters represents a major challenge for asymmetric catalysis. In this paper, the first organocatalytic system that could be used for the asymmetric hydrosilylation of N-unsubstituted β-enamino esters has been developed. Using N-tert-butylsulfinyl-L-proline-derived amides and L-pipecolinic acid-derived formamides as catalyst, a broad range of β-aryl- and β-alkyl-substituted free β-amino esters could be prepared with high yields and enantioselectivities. The practicality was illustrated by the gram-scale asymmetric synthesis of ethyl (R)-3-amino-3-phenylpropanoate and isopropyl (S)-3-amino-4-(2,3,5-trifluorophenyl)butanoate. The resulting product can be smoothly transformed to the FDA approved medicines dapoxetine and sitagliptin in a short synthetic route.

Short synthesis of a proline amide orexin receptor antagonist on the pilot plant scale

A three-step fully telescoped synthesis of an N-sulfonyl proline amide, a nonpeptide antagonist of human orexin receptors, is described. The process development from the medicinal chemistry route up to the 240 kg production of 1 is discussed with a focus

Structure-activity relationship, biological, and pharmacological characterization of the proline sulfonamide ACT-462206: A potent, brain-penetrant dual orexin 1/orexin 2 receptor antagonist

The orexin system consists of two G-protein-coupled receptors, the orexin 1 and orexin 2 receptors, widely expressed in diverse regions of the brain, and two peptide agonists, orexin A and orexin B, which are produced in a small assembly of neurons in the lateral hypothalamus. The orexin system plays an important role in the maintenance of wakefulness. Several compounds (almorexant, SB-649868, suvorexant) have been in advanced clinical trials for treating primary insomnia. ACT-462206 is a new, potent, and selective dual orexin receptor antagonist (DORA) that inhibits the stimulating effects of the orexin peptides at both the orexin 1 and 2 receptors. It decreases wakefulness and increases non-rapid eye movement (non-REM) and REM sleep while maintaining natural sleep architectures in rat and dog electroencephalography/electromyography (EEG/EMG) experiments. ACT-462206 shows anxiolytic-like properties in rats without affecting cognition and motor function. It is therefore a potential candidate for the treatment of insomnia.

Structure-Activity Relationship, Biological, and Pharmacological Characterization of the Proline Sulfonamide ACT-462206: A Potent, Brain-Penetrant Dual Orexin1/Orexin2 Receptor Antagonist

The orexin system consists of two G-protein-coupled receptors, the orexin1 and orexin2 receptors, widely expressed in diverse regions of the brain, and two peptide agonists, orexinA and orexinB, which are produced in a small assembly of neurons in the lat

PROLINE SULFONAMIDE DERIVATIVES AS OREXIN RECEPTOR ANTAGONISTS

The present invention relates to (S)-proline sulfonamide compounds of formula (I) wherein R1 and R2 are as described in the description, or pharmaceutically acceptable salts thereof, for use in the prevention or treatment of diseases

A highly enantioselective organocatalytic method for reduction of aromatic N-alkyl ketimines

A study has demonstrated the development of a highly enantioselective catalytic method for the reduction of aromatic N-alkyl ketimines by trichlorosilane under mild conditions using the newly designed Lewis base organocatalyst that incorporates C- and S-chirality. The S-chiral sulfinamide group in these catalysts plays a crucial role similar to the carboxamide groups as Lewis base for the activation of HSiCl3, and also serves as a source of chirality that the carboxamide group lacks for the asymmetric induction. The results of the study showed that excellent enantioselectivities of up to 99.6% ee and high yields were obtained for a wide range of substrates. Further works is also in progress to clarify the mechanism of the transformation and explore the full application scope of the present catalyst system.

Asymmetric syntheses of N-Boc 2-substituted pyrrolidines and piperidines by intramolecular cyclization

Asymmetric lithiation-substitutions by n-BuLi/(-)-sparteine with the N- Boc-N-(3-halopropyl)allylamines 1-4 provide the N-Boc-2-alkenylpyrrolidines (S)-5, (S)-6, and (S)-7 in yields of 3193% with enantiomeric ratios (ers) from 65:35 to 90:10. These reactions are shown to involve an initial asymmetric deprotonation, but the enantiodetermining step is a subsequent asymmetric cyclization under the influence of the chiral ligand. Extension to formation of a piperidine is illustrated by reaction of N-Boc-(4- chlorobutyl)cinnamylamine (9) to afford (S)-N-Boc-2-(trans-β- styryl)piperidine ((S)-10) in 68% yield with an enantiomeric ratio (er) of 84:16. Analogous reactions with epoxide ring openings of N-Boc-N- (oxaalkenyl)benzylamines 11 and 12 afford the corresponding N-Boc-2-phenyl- 3-(hydroxymethyl)pyrrolidine (13) in 67% yield with a diastereomeric ratio (dr) of 50:50 and ers of 97:3 and 95:5 and the corresponding N-Boc-2-phenyl- 3-(hydroxymethyl)piperidine (14) in 29% yield with a dr of 86:14 and ers of 81:19 and 86:14.