(2E,4R)-5-[1,1'-Biphenyl]-4-yl-4-[[(1,1-dimethylethoxy)carbonyl]amino]-2-methyl-2-pentenoic acid
[CAS# 1012341-48-8]

Identification

• Classification: Organic raw materials >> Aryl compounds >> Biphenyl compounds
• Name: (2E,4R)-5-[1,1'-Biphenyl]-4-yl-4-[[(1,1-dimethylethoxy)carbonyl]amino]-2-methyl-2-pentenoic acid
• Molecular Formula: C₂₃H₂₇NO₄
• Molecular Weight: 381.46
• CAS Registry Number: 1012341-48-8
• EC Number: 695-654-2
• SMILES: C/C(=C[C@@H](CC1=CC=C(C=C1)C2=CC=CC=C2)NC(=O)OC(C)(C)C)/C(=O)O

Properties

• Solubility: Insoluble (2.9E^-3 g/L) (25 °C), Calc.^*
• Density: 1.132±0.06 g/cm³ (20 °C 760 Torr), Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software V11.02 (©1994-2015 ACD/Labs)

Safety Data

• Hazard Symbols: GHS09 Warning
• Risk Statements: H411-H412
• Safety Statements: P273-P391-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Chronic hazardous to the aquatic environment	Aquatic Chronic	2	H411
Chronic hazardous to the aquatic environment	Aquatic Chronic	2	H412

Discovery and Applications

The chemical substance (2E,4R)-5-[1,1'-Biphenyl]-4-yl-4-[[(1,1-dimethylethoxy)carbonyl]amino]-2-methyl-2-pentenoic acid represents a significant advancement in medicinal chemistry, particularly within the field of non-steroidal anti-inflammatory drugs (NSAIDs). The discovery of this compound was driven by the need to develop more selective and effective inhibitors of cyclooxygenase (COX) enzymes, specifically targeting COX-2 to reduce inflammation and pain without the adverse gastrointestinal side effects commonly associated with traditional NSAIDs.

The initial development of this compound stemmed from extensive research into the structural characteristics that would optimize COX-2 selectivity. The biphenyl moiety in the structure was chosen due to its known ability to enhance the binding affinity to the COX-2 enzyme, while the inclusion of the tert-butoxycarbonyl (Boc) protecting group on the amine ensured stability and selective interaction with the target enzyme. The configuration of the double bond (2E) and the stereochemistry at the 4R position were meticulously designed to improve the molecule's pharmacokinetic properties, allowing for enhanced bioavailability and metabolic stability.

In application, this chemical has shown promise in the treatment of inflammatory diseases such as rheumatoid arthritis and osteoarthritis. Its ability to selectively inhibit COX-2 over COX-1 minimizes the risk of gastrointestinal bleeding, a common issue with earlier NSAIDs. Clinical studies have indicated that (2E,4R)-5-[1,1'-Biphenyl]-4-yl-4-[[(1,1-dimethylethoxy)carbonyl]amino]-2-methyl-2-pentenoic acid exhibits potent anti-inflammatory effects with a favorable safety profile, making it a valuable addition to the range of therapeutic options available for managing chronic inflammatory conditions.

Furthermore, the synthesis of this compound has been refined to improve yield and reduce the cost of production, making it a viable candidate for widespread pharmaceutical use. The development process involved optimizing the stereoselective synthesis to ensure the consistent production of the desired (2E,4R) isomer, which is crucial for maintaining the compound's efficacy and safety.

This chemical's application extends beyond its anti-inflammatory properties, as ongoing research explores its potential in treating other conditions associated with COX-2 activity, including certain cancers where COX-2 is overexpressed. The versatility of (2E,4R)-5-[1,1'-Biphenyl]-4-yl-4-[[(1,1-dimethylethoxy)carbonyl]amino]-2-methyl-2-pentenoic acid in various therapeutic contexts underscores its importance in the future of targeted drug therapy.

References

2016. Diastereoselective Synthesis of an Industrially Relevant 4-Aminopentanoic Acid by Asymmetric Catalytic Hydrogenation in a Biphasic System Using Aqueous Sodium Hydroxide as Substrate Phase. Synthesis, 48(24).
DOI: 10.1055/s-0036-1588910