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Two enantiomerically pure cyclic arenesulfonamide hydrochloride salts
Lionel Kiefer1, Philippe Dauban, Robert H Dodd
1Institut de Chimie des Substances Naturelles, UPR 2301, Centre National de la Recherche Scientifique, Bâtiment 27, 1 Avenue de la Terrasse, F-91198 Gif-sur-Yvette, France.
Acta Crystallographica. Section C, Crystal Structure Communications
|February 5, 2009
Summary
Novel cyclic sulfonamides act as agonists for the extracellular calcium sensing receptor (CaSR). Their crystal structures reveal key features, like the absence of pi-pi stacking, distinguishing them from antagonists.
Area of Science:
- Medicinal Chemistry
- Structural Biology
- Pharmacology
Background:
- The extracellular calcium sensing receptor (CaSR) plays a critical role in calcium homeostasis.
- Novel agonists for CaSR are of potential clinical importance for treating various conditions.
Purpose of the Study:
- To determine the crystal structures of two novel cyclic sulfonamide CaSR agonists.
- To elucidate structural features responsible for CaSR agonism and differentiate agonists from antagonists.
Main Methods:
- X-ray crystallography was used to determine the structures of two novel compounds.
- Absolute configuration was assigned based on the known chirality of a precursor molecule.
Main Results:
- The crystal structures of a six-membered and a seven-membered cyclic sulfonamide CaSR agonist were determined.
- A notable absence of intramolecular pi-pi stacking between aromatic groups was observed in both agonists.
- Crystal structures revealed distinct molecular connectivities dominated by chloride-mediated hydrogen bonding.
Conclusions:
- The determined crystal structures provide crucial insights into the molecular recognition of CaSR agonists.
- The absence of intramolecular pi-pi stacking may be a distinguishing feature of CaSR agonists compared to antagonists.
- These findings contribute to the development of new therapeutic agents targeting CaSR.
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