929915-58-2

Usage

Uses

Used in Pharmaceutical Industry:
DG 051 (HCl salt) is used as a therapeutic agent for the development of treatments for cardiovascular diseases and cancers. Its potent inhibition of LTA4H makes it a promising candidate for targeting the synthesis of LTB4, which is involved in various inflammatory and immune responses.
Used in Drug Development:
DG 051 (HCl salt) is used as a lead compound in drug development for the discovery of new therapeutic agents targeting LTA4H. Its unique inhibitory profile and selectivity make it an attractive starting point for the design and optimization of novel drugs with improved potency, selectivity, and pharmacokinetic properties.
Used in Research Applications:
DG 051 (HCl salt) is used as a research tool for studying the role of LTA4H in various biological processes, including inflammation, immune responses, and the synthesis of leukotrienes. It can be employed in biochemical assays, cell-based assays, and animal models to investigate the mechanisms of action and potential therapeutic effects of LTA4H inhibition.
Used in Drug Screening:
DG 051 (HCl salt) is used as a reference compound in high-throughput screening campaigns to identify novel inhibitors of LTA4H and related enzymes. Its well-defined inhibitory profile and selectivity can help in the development of new screening assays and the identification of potential drug candidates with improved therapeutic potential.

Upstream product

• 1198149-97-1 ethyl 4-{(2S)-2-[4-(4-chlorophenoxy)phenoxymethyl]pyrrolidin-1-yl}butyrate 
• 929917-42-0 (S)-2-[4-(4-chlorophenoxy)phenoxymethyl]pyrrolidine-1-carboxylic acid tert-butyl ester 
• 40843-46-7 4-(4-chlorophenoxy)anisole 
• 21567-18-0 4-(4-chlorophenoxy)phenol 
• 106-39-8 bromochlorobenzene 
• 86661-32-7 (S)-tert-butyl 2-((tosyloxy)methyl)pyrrolidine-1-carboxylate 
• 69610-40-8 N-(tert-butoxycarbonyl)-L-prolinol 
• 150-76-5 4-methoxy-phenol 
• 929916-05-2 DG-051 

Downstream Products

• 929916-05-2 DG-051 

Relevant academic research and scientific papers

PROCESS FOR PREPARING 4- { (S) -2- (4-(4-CHLOROPHENOXY) PHENOXYMETHYL) PYRROLIDIN-1-YL) } BUTYRIC ACID AND SALTS THEREOF

The present invention relates to a process for preparing 4-{(S)-2-[4-(4-chlorophenoxy)phenoxymethyl]pyrrolidin-1-yl}butyric acid and its salts.

Discovery of 4-[(2S)-2-{[4-(4-Chlorophenoxy)phenoxy]methyl}-1-pyrrolidinyl] butanoic acid (DG-051) as a novel leukotriene A4 hydrolase inhibitor of leukotriene B4 biosynthesis

Both in-house human genetic and literature data have converged on the identification of leukotriene 4 hydrolase (LTA4H) as a key target for the treatment of cardiovascular disease. We combined fragmentbased crystallography screening with an iterative medicinal chemistry effort to optimize inhibitors of LTA4H. Ligand efficiency was followed throughout our structure-activity studies. As applied within the context of LTA4H inhibitor design, the chemistry team was able to design a potent compound 20 (DG-051) (Kd=26 nM) with high aqueous solubility (>30 mg/mL) and high oral bioavailability (>80% across species) that is currently undergoing clinical evaluation for the treatment of myocardial infarction and stroke. The structural biology-chemistry interaction described in this paper provides a sound alternative to conventional screening techniques. This is the first example of a gene-to-clinic paradigm enabled by a fragment-based drug discovery effort.

Development of a scalable synthetic process for DG-051B, a first-in-class inhibitior of LTA4H

DG-051B is a first-in-class small molecule inhibitor of leukotriene A4 hydrolase (LTA4H), currently in Phase II clinical development for the prevention of heart attack. Process optimization led from a linear seven-step synthetic procedure to a convergent

BIARYL SUBSTITUTED HETEROCYCLE INHIBITORS OF LTA4H FOR TREATING INFLAMMATION

The present invention relates to a chemical genus of biaryl substituted heterocycle inhibitors of LTA4H (leukotriene A4 hydrolase) useful for the treatment and prevention and prophylaxis of inflammatory diseases and disorders. The compounds have general formula Ψ: An example is