214193-10-9

Basic information

• Product Name: N-Boc-L-trans-4,5-methanoproline ethyl ester
• Synonyms: N-Boc-L-trans-4,5-methanoproline ethyl ester;Saxagliptin Impurity 23
• CAS NO: 214193-10-9
• Molecular Formula: C₁₃H₂₁NO₄
• Molecular Weight: 255.31014
• Mol File: 214193-10-9.mol
• Article Data: 4

Chemical Properties

• Appearance: /
• CAS DataBase Reference: N-Boc-L-trans-4,5-methanoproline ethyl ester(CAS DataBase Reference)
• NIST Chemistry Reference: N-Boc-L-trans-4,5-methanoproline ethyl ester(214193-10-9)
• EPA Substance Registry System: N-Boc-L-trans-4,5-methanoproline ethyl ester(214193-10-9)

Safety Data

• Hazardous Substances Data: 214193-10-9(Hazardous Substances Data)

Usage

Description

N-Boc-L-trans-4,5-methanoproline ethyl ester is a chemical compound derived from the amino acid proline, with a Boc-protecting group and an ethyl ester functional group. It is characterized by its unique cyclic structure and is commonly found as an impurity in the synthesis of certain pharmaceutical compounds.

Uses

Used in Pharmaceutical Industry:
N-Boc-L-trans-4,5-methanoproline ethyl ester is used as an impurity in the synthesis of Saxagliptin (S143500), a potent and selective reversible inhibitor of dipeptidyl peptidase-4 (DPP-4). This application is significant because Saxagliptin is an important drug used for the treatment of type 2 diabetes, and the presence of this impurity can affect the drug's efficacy and safety.
In the pharmaceutical industry, controlling the presence of impurities like N-Boc-L-trans-4,5-methanoproline ethyl ester is crucial to ensure the quality, safety, and effectiveness of the final drug product. Researchers and manufacturers work to develop methods for the efficient removal or reduction of such impurities to meet regulatory standards and maintain the desired therapeutic benefits of the drug.

Upstream product

• 24424-99-5 di-tert-butyl dicarbonate 
• 75-11-6 diiodomethane 
• 178172-26-4 (5S)-4,5-dihydro-1H-pyrrol-1,5-dicarboxylic acid [1-(1,1-dimethylethyl)] 5-ethyl ester 
• 144978-35-8 (S)-ethyl N-tert-butoxycarbonylpyroglutamate 
• 194594-23-5 5-hydroxy-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-ethyl ester 

Downstream Products

• 214193-12-1 (1R,3S,5R)-2-azabicyclo[3.1.0]hexane-3 -carboxylic acid 
• 1564265-93-5 (2S,4S,5R)-2-[(2S)-2-amino-2-(3-hydroxyadamantan-1-yl)acetyl]-2-azabicyclo[3.1.0]hexane-3-carbonitrile 
• 1564265-98-0 (R)-3-hydroxyadamantylglycine-L-trans-4,5-methanoprolinenitrile 

Relevant articles and documents

Discovery and Development of 3-(6-Chloropyridine-3-yloxymethyl)-2-azabicyclo[3.1.0]hexane Hydrochloride (SUVN-911): A Novel, Potent, Selective, and Orally Active Neuronal Nicotinic Acetylcholine α4β2 Receptor Antagonist for the Treatment of Depression

A series of chemical optimizations guided by in vitro affinity at the α4β2 receptor in combination with selectivity against the α3β4 receptor, pharmacokinetic evaluation, and in vivo efficacy in a forced swim test resulted in identification of 3-(6-chloropyridine-3-yloxymethyl)-2-azabicyclo[3.1.0]hexane hydrochloride (9h, SUVN-911) as a clinical candidate. Compound 9h is a potent α4β2 receptor ligand with a Ki value of 1.5 nM. It showed >10 μM binding affinity toward the ganglionic α3β4 receptor apart from showing selectivity over 70 other targets. It is orally bioavailable and showed good brain penetration in rats. Marked antidepressant activity and dose-dependent receptor occupancy in rats support its potential therapeutic utility in the treatment of depression. It does not affect the locomotor activity at doses several folds higher than its efficacy dose. It is devoid of cardiovascular and gastrointestinal side effects. Successful long-term safety studies in animals and phase-1 evaluation in healthy humans for safety, tolerability, and pharmacokinetics paved the way for its further development.

Core modification of substituted piperidines as Novel inhibitors of HDM2-p53 protein-protein interaction

The discovery of 3,3-disubstituted piperidine 1 as novel p53-HDM2 inhibitors prompted us to implement subsequent SAR follow up directed towards piperidine core modifications. Conformational restrictions and further functionalization of the piperidine core were investigated as a strategy to gain additional interactions with HDM2. Substitutions at positions 4, 5 and 6 of the piperidine ring were explored. Although some substitutions were tolerated, no significant improvement in potency was observed compared to 1. Incorporation of an allyl side chain at position 2 provided a drastic improvement in binding potency.