(1S,3R)-2-(2-Chloroacetyl)-2,3,4,9-tetrahydro-1-[4-(methoxycarbonyl)phenyl]-1H-pyrido[3,4-b]indole-3-carboxylic acid methyl ester
[CAS# 1219810-16-8]

Identification

• Classification: Organic raw materials >> Heterocyclic compound >> Indoles
• Name: (1S,3R)-2-(2-Chloroacetyl)-2,3,4,9-tetrahydro-1-[4-(methoxycarbonyl)phenyl]-1H-pyrido[3,4-b]indole-3-carboxylic acid methyl ester
• Synonyms: 1S,3R-RSL 3
• Molecular Formula: C₂₃H₂₁ClN₂O₅
• Molecular Weight: 440.88
• CAS Registry Number: 1219810-16-8
• SMILES: COC(=O)[C@H]1CC2=C([C@@H](N1C(=O)CCl)C3=CC=C(C=C3)C(=O)OC)NC4=CC=CC=C24

Properties

• Density: 1.4±0.1 g/cm³ Calc.^*
• Boiling point: 641.3±55.0 ºC 760 mmHg (Calc.)^*
• Flash point: 341.6±31.5 ºC (Calc.)^*
• Solubility: 100 mM (DMSO} (Expl.)
• Index of refraction: 1.636 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H302-H315-H319-H335
• Precautionary Statements: P261-P305+P351+P338

Discovory and Applicatios

(1S,3R)-2-(2-Chloroacetyl)-2,3,4,9-tetrahydro-1-\[4-(methoxycarbonyl)phenyl]-1H-pyrido\[3,4-b]indole-3-carboxylic acid methyl ester is a chemically synthesized compound that belongs to the class of substituted tetrahydro-β-carboline derivatives. It features a complex tricyclic structure with specific stereochemistry at positions 1 and 3, where the (1S,3R) configuration is critical for its biological activity. The compound contains functional groups such as a chloroacetyl moiety, ester groups, and a substituted phenyl ring, which contribute to its chemical reactivity and potential interaction with biological targets.

The discovery and development of such derivatives are rooted in medicinal chemistry programs aimed at synthesizing molecules capable of modulating cellular pathways through enzyme or receptor interactions. The structural core of the molecule, a tetrahydro-β-carboline framework fused with a pyridine and indole system, is known for its biological significance and is found in various natural products and pharmacologically active compounds. This framework has attracted interest due to its ability to cross the blood-brain barrier and its potential involvement in modulating neurotransmitter systems.

In laboratory settings, (1S,3R)-2-(2-Chloroacetyl)-2,3,4,9-tetrahydro-1-\[4-(methoxycarbonyl)phenyl]-1H-pyrido\[3,4-b]indole-3-carboxylic acid methyl ester has been investigated primarily as a synthetic intermediate or a test molecule in pharmacological research. The presence of the chloroacetyl group offers a point of reactivity for further chemical derivatization or for interaction with nucleophilic residues in proteins, potentially allowing the compound to function as an irreversible inhibitor of enzymatic activity under specific conditions. The methoxycarbonylphenyl group contributes to the compound’s lipophilicity and may affect its pharmacokinetics in biological systems.

While direct clinical applications of this specific compound are limited due to its specialized nature, compounds of this type have served as valuable tools in structure-activity relationship (SAR) studies. They are used to probe the pharmacophore requirements of receptors, particularly in areas involving neuropharmacology or oncology, where β-carboline structures have demonstrated modulatory activity. Research involving these molecules often focuses on binding affinity, selectivity for enzyme targets, and cytotoxicity profiles, which inform the design of second-generation analogs with improved potency or safety.

Synthetic access to this compound involves multi-step organic synthesis, typically beginning with the formation of the tetrahydro-β-carboline scaffold through Pictet–Spengler-type cyclization, followed by selective functionalization of the indole and pyridine rings. The stereoselective introduction of the (1S,3R) centers may involve chiral auxiliaries or asymmetric catalysis, and the final steps include esterification and acylation reactions to introduce the functional side chains.

In addition to use in SAR studies, such compounds may also be screened in cell-based assays for their ability to interfere with cellular pathways related to proliferation, apoptosis, or inflammation. The chloroacetyl group has particular relevance in designing inhibitors that target cysteine residues within enzyme active sites, potentially leading to covalent modification and enzyme inhibition.

The development and application of (1S,3R)-2-(2-Chloroacetyl)-2,3,4,9-tetrahydro-1-\[4-(methoxycarbonyl)phenyl]-1H-pyrido\[3,4-b]indole-3-carboxylic acid methyl ester highlight the role of chemical synthesis in expanding the toolkit of bioactive small molecules. Through structural modification and pharmacological testing, such compounds contribute to the broader understanding of molecular recognition and therapeutic intervention strategies.

References

2014. Regulation of Ferroptotic Cancer Cell Death by GPX4. Cell, 156(1-2).
DOI: 10.1016/j.cell.2013.12.010

2021. Discovery of a Potent Glutathione Peroxidase 4 Inhibitor as a Selective Ferroptosis Inducer. Journal of Medicinal Chemistry, 64(17).
DOI: 10.1021/acs.jmedchem.1c00569

2024. Ferroptosis mechanisms and regulations in cardiovascular diseases. Cell Biology and Toxicology, 40(1).
DOI: 10.1007/s10565-024-09853-w