157115-85-0

Basic information

• Product Name: ethyl 2-[[(2S)-1-(2-phenylacetyl)pyrrolidine-2-carbonyl]amino]acetate
• Synonyms: ethyl 2-[[(2S)-1-(2-phenylacetyl)pyrrolidine-2-carbonyl]amino]acetate;N-(1-(Phenylacetyl)-L-prolyl)glycine ethyl ester;Noopept;(S)-ethyl 2-(1-(2-phenylacetyl)pyrrolidine-2-carboxaMido)acetate;SGS 111;SGS111;SGS-111;1-(2-Phenylacetyl)-L-prolylglycine Ethyl Ester
• CAS NO: 157115-85-0
• Molecular Formula: C₁₇H₂₂N₂O₄
• Molecular Weight: 318.37
• EINECS: 1592732-453-0
• Product Categories: pharmaceutical intermediate and medicine grade
• Mol File: 157115-85-0.mol

Chemical Properties

• Melting Point: 94.0 to 98.0 °C
• Boiling Point: 547.3°Cat760mmHg
• Flash Point: 284.8°C
• Appearance: white powder
• Density: 1.202g/cm³
• Vapor Pressure: 4.93E-12mmHg at 25°C
• Refractive Index: 1.548
• Storage Temp.: -20°C
• Solubility: Soluble in DMSO (up to 25 mg/ml)
• PKA: 13.41±0.20(Predicted)
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 2 months.
• CAS DataBase Reference: ethyl 2-[[(2S)-1-(2-phenylacetyl)pyrrolidine-2-carbonyl]amino]acetate(CAS DataBase Reference)
• NIST Chemistry Reference: ethyl 2-[[(2S)-1-(2-phenylacetyl)pyrrolidine-2-carbonyl]amino]acetate(157115-85-0)
• EPA Substance Registry System: ethyl 2-[[(2S)-1-(2-phenylacetyl)pyrrolidine-2-carbonyl]amino]acetate(157115-85-0)

Safety Data

• RTECS: MC0814400
• Hazardous Substances Data: 157115-85-0(Hazardous Substances Data)

Usage

Uses

Used in Cognitive Enhancement:
Ethyl 2-[[(2S)-1-(2-phenylacetyl)pyrrolidine-2-carbonyl]amino]acetate is used as a cognitive enhancer for improving memory, learning, and focus. Its potent effects make it a popular choice for individuals seeking a mild cognitive boost and increased mental clarity.
Used in Antioxidant Applications:
As a powerful antioxidant, ethyl 2-[[(2S)-1-(2-phenylacetyl)pyrrolidine-2-carbonyl]amino]acetate helps prevent neurological disorders and supports brain growth. This property is thought to contribute to the improvement of long-term memory.
Used in Pharmaceutical Industry:
Ethyl 2-[[(2S)-1-(2-phenylacetyl)pyrrolidine-2-carbonyl]amino]acetate is used as a potential treatment for Alzheimer's disease due to its promising results in human studies. Its ability to enhance memory and protect against neurological disorders makes it a valuable candidate for further research and development in the pharmaceutical industry.
Used in Nootropic Formulations:
In the nootropic industry, ethyl 2-[[(2S)-1-(2-phenylacetyl)pyrrolidine-2-carbonyl]amino]acetate is used as an active ingredient in nootropic supplements. Its high potency and cognitive-enhancing properties make it a sought-after component in formulations aimed at improving cognitive function and overall brain health.
Used in Research and Development:
Ethyl 2-[[(2S)-1-(2-phenylacetyl)pyrrolidine-2-carbonyl]amino]acetate is used in research and development for its potential applications in various fields, including neuroscience, pharmacology, and cognitive enhancement. Its unique properties and high potency make it an interesting subject for further study and potential development of new therapeutic agents.

History

Noopept (previously GVS-111) is a nootropic developed at the Zakusov Institute of Pharmacology (Russian Academy of Medical Sciences) by T. A. Gudasheva. It is one of several nootropics developed based on the structure of piracetam. Its advantage over piracetam is that it can be taken at a lower dose.Noopept is a popular cognitive-enhancing supplement in the nootropic community. Proposed mechanism of actions based on preclinical studies include increasing acetylcholine signaling, increasing the expression of BDNF and NGF, protecting from glutamate toxicity, and increasing inhibitory neurotransmission in the brain.www.alzdiscovery.org

Biochem/physiol Actions

Noopept is a nootropic and neuroprotective drug that normalizes the balance of the pro- and antioxidant systems. Noopept modulates a variety of physiological functions including cognition and anxiety. Noopept significantly weakens streptozotocin-Induced diabetes in rats.

Side effects

Noopept is associated with some mild side effects based on limited clinical evidence. possible side effects of noopept included sleep disturbances (5/31 patients), irritability (3/31), and increased blood pressure (7/31) (Neznamov and Teleshova, 2009).

Preparation

Noopept (ethyl ester of N-phenylacetyl-L-prolylglycine) was designed as a drug at State Zakusov Institute of Pharmacology. The synthesis of the drug is based on the original hypothesis of peptide design, according to which structures similar to known psychotropic agents are reproduced using appropriate amino acids. The non-peptide prototype of Noopept is the nootropic drug Piracetam.1. Perform the carboxylation of N-phenylacetyl-L-proline and ethyl glycine in the presence of isobutyl chloroformate. 2. Add slowly isobutyl chloroformate (1.17 g, 8.6 mmol) to a solution of N-phenylacetyl-L-proline (2.0 g, 8.6 mmol) dissolved in a mixed solvent of THF and dichloromethane (1:1; THF/dichloromethane (v/v)).3.Stir the mixture for 4 h at 0 ～5 °CMolecular Mechanism Underlying the Action of Substituted Pro-Gly Dipeptide Noopept

References

1) Ostrovskaya et al. (2007), The nootropic and neuroprotective proline-containing dipeptide noopept restores spatial memory and increases immunoreactivity to amyloid in an Alzheimer’s disease model; J. Psychopharmacol., 21 6112) Jia et al. (2011), Neuroprotective and nootropic drug noopept rescues α-synuclein amyloid cytotoxicity; J. Mol. Biol., 414 6993) Ostrovskaya et al. (2008), Noopept stimulates the expression of NGF and BDNF in rat hippocampus; Bull. Exp. Biol. Med., 146 3344) Antipova et al. (2016), Dipeptide Piracetam Analogue Noopept Improves Viability of Hippocampal HT-22 Neurons in the Glutamate Toxicity Model; Bull. Exp. Biol. Med., 161 585) Ostrovskaya et al. (2014), Comparative activity of proline-containing dipeptide noopept and inhibitor of dipeptidyl peptidase-4 sitagliptin in a rat model of developing diabetes; Bull. Exp. Biol. Med., 156 342

InChI:InChI=1/C17H22N2O4/c1-2-23-16(21)12-18-17(22)14-9-6-10-19(14)15(20)11-13-7-4-3-5-8-13/h3-5,7-8,14H,2,6,9-12H2,1H3,(H,18,22)/t14-/m0/s1

Synthetic route

glycine ethyl ester hydrochloride (623-33-6) + C18H23NO4 → N-phenylacetyl-L-prolylglycine ethyl ester (157115-85-0)

Conditions	Yield
With 4-methyl-morpholine In chloroform; N,N-dimethyl-formamide at -5 - 20℃; for 1.5h; Yield given;

(S)-1-(2-phenylacetyl)pyrrolidine-2-carboxylic acid (2752-38-7) → N-phenylacetyl-L-prolylglycine ethyl ester (157115-85-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: N-methylmorpholine / CHCl3 / 0.03 h / -10 °C 2: N-methylmorpholine / CHCl3; dimethylformamide / 1.5 h / -5 - 20 °C View Scheme

phenylacetyl chloride (103-80-0) + lead (II)-compound of ethanethiol → N-phenylacetyl-L-prolylglycine ethyl ester (157115-85-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: 86 percent / aq. NaOH / 0.25 h / 0 - 4 °C 2: N-methylmorpholine / CHCl3 / 0.03 h / -10 °C 3: N-methylmorpholine / CHCl3; dimethylformamide / 1.5 h / -5 - 20 °C View Scheme

L-proline (147-85-3) → N-phenylacetyl-L-prolylglycine ethyl ester (157115-85-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: 86 percent / aq. NaOH / 0.25 h / 0 - 4 °C 2: N-methylmorpholine / CHCl3 / 0.03 h / -10 °C 3: N-methylmorpholine / CHCl3; dimethylformamide / 1.5 h / -5 - 20 °C View Scheme

methylamine (74-89-5) + N-phenylacetyl-L-prolylglycine ethyl ester (157115-85-0) → N-phenylacetyl-L-prolylglycine methylamine

Conditions	Yield
In methanol Ambient temperature;	99%

N-phenylacetyl-L-prolylglycine ethyl ester (157115-85-0) → N-phenylacetyl-L-prolylglycine amide

Conditions	Yield
With ammonia In methanol Ambient temperature;	95%

N-phenylacetyl-L-prolylglycine ethyl ester (157115-85-0) → N-phenylacetyl-L-prolylglycine (157115-95-2)

Conditions	Yield
With sodium hydroxide for 3h;	89.9%

N-phenylacetyl-L-prolylglycine ethyl ester (157115-85-0) → N-phenylacetyl-L-prolylglycine dimethylamide

Conditions	Yield
Multi-step reaction with 3 steps 1: 89.9 percent / 1 N aq. NaOH / 3 h 2: ethylmorpholine / dimethylformamide / 0.03 h / -10 °C 3: dimethylformamide / 0.5 h / -5 °C View Scheme

N-phenylacetyl-L-prolylglycine ethyl ester (157115-85-0) → C20H26N2O6

Conditions	Yield
Multi-step reaction with 2 steps 1: 89.9 percent / 1 N aq. NaOH / 3 h 2: ethylmorpholine / dimethylformamide / 0.03 h / -10 °C View Scheme

Upstream product

• 147-85-3 L-proline 
• 103-80-0 phenylacetyl chloride 
• 2752-38-7 (S)-1-(2-phenylacetyl)pyrrolidine-2-carboxylic acid 
• 623-33-6 glycine ethyl ester hydrochloride 

Downstream Products

• 157115-95-2 N-phenylacetyl-L-prolylglycine 

Relevant articles and documents

Synthesis and antiamnesic activity of a series of N-acylprolyl-containing dipeptides

Eaters and amides of a series of N-acylprolyl-containing dipeptides were synthesized. It was established that these substances possess the ability to prevent memory decline evoked by maximal electroshock (MES) in a passive avoidance step-through paradigm. These N-acylprolyl-containing dipeptides were designed as analogues of pyroglutamyl-containing dipeptides, which we previously demonstrated to be highly active nootropics. Among the structure-activity relationships explored were the effect of N-acylsubstitution size, C-terminal substitution and the nature of the second amino acid. The optimal N-acyl moiety was the N-phenyl-acetyl group, while the optimal C-terminal substitution-esters were those derived from low alkyl alcohols. The optimal second amino acids were Asp, Glu or their fragments, Gly, β-Ala, GABA. Compound 1 (N-phenylacetylprolylglycine ethyl eater) was selected for further evalution in impaired cognitive functions. It was supposed that esters and unsubstituted amides of N-acylprolylglycines are prodrugs, which convert to the bioactive cyclo-(Pro-Gly) by virtue of enzymatic or chemical lability within the body.