Substituted Indole-5-carboxamides and -acetamides as Potent Nonpeptide GnRH Receptor Antagonists

The 2-aryltryptamine class of GnRH receptor antagonists has been modified to incorporate carboxamide and acetamide substituents at the indole 5-position. With either a phenol or methanesulfonamide terminus on the N-aralkyl side chain, potent binding affinity to the GnRH receptor was achieved. A func...

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Veröffentlicht in:Bioorganic & medicinal chemistry letters 2001-07, Vol.11 (13), p.1723-1726
Hauptverfasser: Ashton, Wallace T., Sisco, Rosemary M., Yang, Yi Tien, Lo, Jane-Ling, Yudkovitz, Joel B., Cheng, Kang, Goulet, Mark T.
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Sprache:eng
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Zusammenfassung:The 2-aryltryptamine class of GnRH receptor antagonists has been modified to incorporate carboxamide and acetamide substituents at the indole 5-position. With either a phenol or methanesulfonamide terminus on the N-aralkyl side chain, potent binding affinity to the GnRH receptor was achieved. A functional assay for GnRH antagonism was even more sensitive to structural modification and revealed a strong preference for branched tertiary amides. The 2-aryltryptamine class of GnRH receptor antagonists has been modified to incorporate carboxamide and acetamide substituents at the indole 5-position. With either a phenol or methanesulfonamide terminus on the N-aralkyl side chain, potent binding affinity to the GnRH receptor was achieved. A functional assay for GnRH antagonism was even more sensitive to structural modification and revealed a strong preference fro branched chain amides such as 28 and 45.
ISSN:0960-894X
1464-3405
DOI:10.1016/S0960-894X(01)00274-8