| Title : Novel oxazolidinone calcitonin gene-related peptide (CGRP) receptor antagonists for the acute treatment of migraine - Crowley_2015_Bioorg.Med.Chem.Lett_25_4777 |
| Author(s) : Crowley BM , Stump CA , Nguyen DN , Potteiger CM , McWherter MA , Paone DV , Quigley AG , Bruno JG , Cui D , Culberson JC , Danziger A , Fandozzi C , Gauvreau D , Kemmerer AL , Menzel K , Moore EL , Mosser SD , Reddy V , White RB , Salvatore CA , Kane SA , Bell IM , Selnick HG , Fraley ME , Burgey CS |
| Ref : Bioorganic & Medicinal Chemistry Lett , 25 :4777 , 2015 |
|
Abstract :
In our efforts to develop CGRP receptor antagonists as backups to MK-3207, 2, we employed a scaffold hopping approach to identify a series of novel oxazolidinone-based compounds. The development of a structurally diverse, potent (20, cAMP+HS IC50=0.67nM), and selective compound (hERG IC50=19muM) with favorable rodent pharmacokinetics (F=100%, t1/2=7h) is described. Key to this development was identification of a 3-substituted spirotetrahydropyran ring that afforded a substantial gain in potency (10 to 35-fold). |
| PubMedSearch : Crowley_2015_Bioorg.Med.Chem.Lett_25_4777 |
| PubMedID: 26231160 |
Crowley BM, Stump CA, Nguyen DN, Potteiger CM, McWherter MA, Paone DV, Quigley AG, Bruno JG, Cui D, Culberson JC, Danziger A, Fandozzi C, Gauvreau D, Kemmerer AL, Menzel K, Moore EL, Mosser SD, Reddy V, White RB, Salvatore CA, Kane SA, Bell IM, Selnick HG, Fraley ME, Burgey CS (2015)
Novel oxazolidinone calcitonin gene-related peptide (CGRP) receptor antagonists for the acute treatment of migraine
Bioorganic & Medicinal Chemistry Lett
25 :4777
Crowley BM, Stump CA, Nguyen DN, Potteiger CM, McWherter MA, Paone DV, Quigley AG, Bruno JG, Cui D, Culberson JC, Danziger A, Fandozzi C, Gauvreau D, Kemmerer AL, Menzel K, Moore EL, Mosser SD, Reddy V, White RB, Salvatore CA, Kane SA, Bell IM, Selnick HG, Fraley ME, Burgey CS (2015)
Bioorganic & Medicinal Chemistry Lett
25 :4777