Details

Autor(en) / Beteiligte

• Stump, Craig A.
• Bell, Ian M.
• Bednar, Rodney A.
• Bruno, Joseph G.
• Fay, John F.
• Gallicchio, Steven N.
• Johnston, Victor K.
• Moore, Eric L.
• Mosser, Scott D.
• Quigley, Amy G.
• Salvatore, Christopher A.
• Theberge, Cory R.
• Blair Zartman, C.
• Zhang, Xu-Fang
• Kane, Stefanie A.
• Graham, Samuel L.
• Vacca, Joseph P.
• Williams, Theresa M.

Titel

The discovery of highly potent CGRP receptor antagonists

Ist Teil von

• Bioorganic & medicinal chemistry letters, 2009, Vol.19 (1), p.214-217

Ort / Verlag

Amsterdam: Elsevier Ltd

Erscheinungsjahr

2009

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Rational modification of a previously identified spirohydantoin lead structure has identified a series of potent spiroazaoxindole CGRP receptor antagonists. The azaoxindole was found to be a general replacement for the hydantoin that consistently improved in vitro potency. The combination of the indanylspiroazaoxindole and optimized benzimidazolinones led to highly potent antagonists (e.g., 25, CGRP K i = 40 pM). The closely related compound 27 demonstrated good oral bioavailability in dog and rhesus.