Abstract:
:We have synthesized several C7-spirocyclic analogues of vorapaxar and evaluated their in vitro activities against PAR-1 receptor. Some of these analogues showed activities and rat plasma levels comparable to vorapaxar. Compound 5c from this series showed excellent PAR-1 activity (K i = 5.1 nM). We also present a model of these spirocyclic compounds docked to the PAR-1 receptor based on the X-ray crystal structure of vorapaxar bound to PAR-1 receptor. This model explains some of the structure-activity relationships in this series.
journal_name
ACS Med Chem Lettjournal_title
ACS medicinal chemistry lettersauthors
Chelliah MV,Eagen K,Guo Z,Chackalamannil S,Xia Y,Tsai H,Greenlee WJ,Ahn HS,Kurowski S,Boykow G,Hsieh Y,Chintala Mdoi
10.1021/ml500008wsubject
Has Abstractpub_date
2014-03-11 00:00:00pages
561-5issue
5issn
1948-5875journal_volume
5pub_type
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