Himbacine derived thrombin receptor (PAR-1) antagonists: Structure-activity relationship of the lactone ring

Bioorganic and Medicinal Chemistry Letters

Volumn 16, Issue 18, 2006, Pages 4969-4972

  Xia, Yan ^a   Chackalamannil, Samuel ^a   Chan, Tze Ming ^a   Czarniecki, Michael ^a   Doller, Darío ^a   Eagen, Keith ^a   Greenlee, William J ^a   Tsai, Hsingan ^a   Wang, Yuguang ^a   Ahn, Ho Sam ^a   Boykow, George C ^a   McPhail, Andrew T ^b  

^a MERCK RESEARCH LABORATORIES   (United States)

^b DUKE UNIVERSITY   (United States)

Author keywords

Himbacine; PAR 1 Antagonist; Structure activity relationship; Thrombin receptor antagonist

Indexed keywords

HIMBACINE; LACTONE DERIVATIVE; PROTEINASE ACTIVATED RECEPTOR 1; PYRIDINE DERIVATIVE; RECEPTOR BLOCKING AGENT;

ARTICLE; BINDING AFFINITY; HUMAN; HUMAN CELL; MICHAEL ADDITION; STEREOCHEMISTRY; STRUCTURE ACTIVITY RELATION; TEMPERATURE;

ALKALOIDS; FURANS; INHIBITORY CONCENTRATION 50; LACTONES; MOLECULAR STRUCTURE; NAPHTHALENES; PIPERIDINES; RECEPTOR, PAR-1; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 33746835744     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2006.06.042     Document Type: Article

References (18)

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17. 50 < 100 nM) were assayed multiple times (n ≥ 5, SD ± 20%).
18. Compound 3 was included for reference. From our unpublished results the SAR in the unsaturated tricyclic lactone series generally parallels that in the saturated series with ca. 2-fold decreases in binding potency.