Halide salts of antimigraine agents eletriptan and naratriptan

Area of Science:

• Medicinal Chemistry
• Structural Biology
• Pharmacology

Background:

• Triptans are a class of drugs used to treat migraines.
• Understanding the molecular structure and conformation of triptans is crucial for optimizing their therapeutic efficacy.
• Eletriptan hydrobromide monohydrate and naratriptan hydrochloride are key triptan compounds.

Purpose of the Study:

• To elucidate the distinct molecular conformations of eletriptan hydrobromide monohydrate and naratriptan hydrochloride.
• To investigate the hydrogen-bonding networks and crystal packing in these triptan molecules.
• To provide insights into structure-activity relationships for the triptan class to aid drug development.

Main Methods:

• X-ray crystallography was employed to determine the three-dimensional structures of eletriptan hydrobromide monohydrate and naratriptan hydrochloride.
• Analysis of molecular conformations, including substituent orientations relative to the indole ring.
• Detailed examination of hydrogen-bonding interactions involving protonated nitrogen atoms, counterions, and solvent molecules.

Main Results:

• Both eletriptan and naratriptan adopt conformations similar to other triptans, with protonated nitrogen atoms involved in hydrogen bonding.
• Eletriptan hydrobromide monohydrate exhibits indole ring substituents on opposite sides of the ring plane, with water molecules forming helical chains.
• Naratriptan hydrochloride shows indole ring substituents on the same side, and chloride ions form macrocyclic ring motifs creating sheet-like structures.

Conclusions:

• The distinct conformational preferences and hydrogen-bonding patterns of eletriptan and naratriptan provide valuable structure-activity relationship data.
• This detailed structural understanding can guide the design of novel triptan-based therapeutics with improved pharmacological profiles.
• The findings contribute to the broader knowledge of molecular interactions relevant to drug development in the triptan class.