| Title : Identification of potent, highly constrained CGRP receptor antagonists - Stump_2010_Bioorg.Med.Chem.Lett_20_2572 |
| Author(s) : Stump CA , Bell IM , Bednar RA , Fay JF , Gallicchio SN , Hershey JC , Jelley R , Kreatsoulas C , Moore EL , Mosser SD , Quigley AG , Roller SA , Salvatore CA , Sharik SS , Theberge CR , Zartman CB , Kane SA , Graham SL , Selnick HG , Vacca JP , Williams TM |
| Ref : Bioorganic & Medicinal Chemistry Lett , 20 :2572 , 2010 |
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Abstract :
A novel series of potent CGRP receptor antagonists containing a central quinoline ring constraint was identified. The combination of the quinoline constraint with a tricyclic benzimidazolinone left hand fragment produced an analog with picomolar potency (14, CGRP K(i)=23 pM). Further optimization of the tricycle produced a CGRP receptor antagonist that exhibited subnanomolar potency (19, CGRP K(i)=0.52 nM) and displayed a good pharmacokinetic profile in three preclinical species. |
| PubMedSearch : Stump_2010_Bioorg.Med.Chem.Lett_20_2572 |
| PubMedID: 20299218 |
Stump CA, Bell IM, Bednar RA, Fay JF, Gallicchio SN, Hershey JC, Jelley R, Kreatsoulas C, Moore EL, Mosser SD, Quigley AG, Roller SA, Salvatore CA, Sharik SS, Theberge CR, Zartman CB, Kane SA, Graham SL, Selnick HG, Vacca JP, Williams TM (2010)
Identification of potent, highly constrained CGRP receptor antagonists
Bioorganic & Medicinal Chemistry Lett
20 :2572
Stump CA, Bell IM, Bednar RA, Fay JF, Gallicchio SN, Hershey JC, Jelley R, Kreatsoulas C, Moore EL, Mosser SD, Quigley AG, Roller SA, Salvatore CA, Sharik SS, Theberge CR, Zartman CB, Kane SA, Graham SL, Selnick HG, Vacca JP, Williams TM (2010)
Bioorganic & Medicinal Chemistry Lett
20 :2572