Design and synthesis of cyclic sulfonamides and sulfamates as new calcium sensing receptor agonists

Bioorg Med Chem Lett. 2010 Dec 15;20(24):7483-7. doi: 10.1016/j.bmcl.2010.10.006. Epub 2010 Oct 30.

Abstract

The design, synthesis and calcimimetic properties of various cyclic sulfonamides and sulfamates are described. The latter were prepared from the corresponding o-alkenylarenesulfonamides via copper- or rhodium-catalyzed intramolecular aziridination. The size of the cyclic sulfonamide rings as well as the position of the crucial (R)-naphthylethylamine substituent significantly affected calcimimetic activity. The most active compounds were the six- and seven-membered sulfonamides 30a and 31a and sulfamate 34a.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcimimetic Agents / chemical synthesis*
  • Calcimimetic Agents / chemistry
  • Calcimimetic Agents / pharmacology
  • Catalysis
  • Copper / chemistry
  • Crystallography, X-Ray
  • Cyclization
  • Drug Design
  • Humans
  • Molecular Conformation
  • Mutation
  • Rats
  • Receptors, Calcium-Sensing / agonists*
  • Receptors, Calcium-Sensing / genetics
  • Receptors, Calcium-Sensing / metabolism
  • Rhodium / chemistry
  • Stereoisomerism
  • Structure-Activity Relationship
  • Sulfonamides / chemical synthesis
  • Sulfonamides / chemistry*
  • Sulfonamides / pharmacology
  • Sulfonic Acids / chemical synthesis
  • Sulfonic Acids / chemistry*
  • Sulfonic Acids / pharmacology

Substances

  • Calcimimetic Agents
  • Receptors, Calcium-Sensing
  • Sulfonamides
  • Sulfonic Acids
  • Copper
  • sulfamic acid
  • Rhodium