| Title : The discovery of highly potent CGRP receptor antagonists - Stump_2009_Bioorg.Med.Chem.Lett_19_214 |
| Author(s) : Stump CA , Bell IM , Bednar RA , Bruno JG , Fay JF , Gallicchio SN , Johnston VK , Moore EL , Mosser SD , Quigley AG , Salvatore CA , Theberge CR , Blair Zartman C , Zhang XF , Kane SA , Graham SL , Vacca JP , Williams TM |
| Ref : Bioorganic & Medicinal Chemistry Lett , 19 :214 , 2009 |
|
Abstract :
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)=40pM). The closely related compound 27 demonstrated good oral bioavailability in dog and rhesus. |
| PubMedSearch : Stump_2009_Bioorg.Med.Chem.Lett_19_214 |
| PubMedID: 19010673 |
Stump CA, Bell IM, Bednar RA, Bruno JG, Fay JF, Gallicchio SN, Johnston VK, Moore EL, Mosser SD, Quigley AG, Salvatore CA, Theberge CR, Blair Zartman C, Zhang XF, Kane SA, Graham SL, Vacca JP, Williams TM (2009)
The discovery of highly potent CGRP receptor antagonists
Bioorganic & Medicinal Chemistry Lett
19 :214
Stump CA, Bell IM, Bednar RA, Bruno JG, Fay JF, Gallicchio SN, Johnston VK, Moore EL, Mosser SD, Quigley AG, Salvatore CA, Theberge CR, Blair Zartman C, Zhang XF, Kane SA, Graham SL, Vacca JP, Williams TM (2009)
Bioorganic & Medicinal Chemistry Lett
19 :214