Design and synthesis of cyclic sulfonamides and sulfamates as new calcium sensing receptor agonists.
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.
Institut de Chimie des Substances Naturelles, UPR 2301, Centre National de la Recherche Scientifique, Gif-sur-Yvette, France.
Lionel
L
Kiefer
Tatiana
T
Gorojankina
Philippe
P
Dauban
Hélène
H
Faure
Martial
M
Ruat
Robert H
RH
Dodd
D000818:Animals; D057966:Calcimimetic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002384:Catalysis; D003300:Copper / Q000737:chemistry; D018360:Crystallography, X-Ray; D003500:Cyclization; D015195:Drug Design; D006801:Humans; D008968:Molecular Conformation; D009154:Mutation; D051381:Rats; D044169:Receptors, Calcium-Sensing / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D012238:Rhodium / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013451:Sulfonic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
D057966:Calcimimetic Agents; D044169:Receptors, Calcium-Sensing; D013449:Sulfonamides; D013451:Sulfonic Acids; D003300:Copper; C005741:sulfamic acid; D012238:Rhodium