3-Acrylamide-4-aryloxyindoles: Synthesis, biological evaluation and metabolic stability of potent and selective EP3 receptor antagonists

Bioorganic and Medicinal Chemistry Letters

Volumn 19, Issue 5, 2009, Pages 1528-1531

  Zhou, Nian ^a   Zeller, Wayne ^a   Zhang, Jun ^a   Onua, Emmanuel ^a   Kiselyov, Alex S ^a   Ramirez, Jose ^b   Palsdottir, Gudrún ^b   Halldorsdottir, Gudrún ^b   Andrésson, Thorkell ^b   Gurney, Mark E ^b   Singh, Jasbir ^a  

^a DeCODE Chemistry & Biostructures   (United States)

^b DECODE GENETICS   (Iceland)

Author keywords

Acylsulfonamide; EP3 receptor antagonists; Peri substituted indoles; Prostanoid receptor antagonists

Indexed keywords

ANTICOAGULANT AGENT; INDOLE DERIVATIVE; PROSTAGLANDIN E3; PROSTAGLANDIN RECEPTOR BLOCKING AGENT;

ANIMAL CELL; ARTICLE; BIOASSAY; DRUG METABOLISM; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SELECTIVITY; DRUG SYNTHESIS; HUMAN; NONHUMAN; PHARMACOPHORE; RAT; THROMBOCYTE AGGREGATION;

ACRYLAMIDES; ANIMALS; CHO CELLS; CRICETINAE; CRICETULUS; DOGS; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG EVALUATION, PRECLINICAL; DRUG STABILITY; HAPLORHINI; HUMANS; INDOLES; MICE; RATS; RECEPTORS, PROSTAGLANDIN E;

RATTUS;

EID: 60449111749     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2008.12.112     Document Type: Article

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22. 3 receptor in the presence of 0.05% HSA. This data indicates a propensity of these compounds to strongly bind to serum proteins. Hence, we found it imperative to routinely screen each strongly potent compound from the normal buffer assay in the presence of 10% human serum to provide useful information on the free fraction of the compound available for future in vivo examinations.
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24. 50 in the rat platelet aggregation studies of 358 nM and 136 nM, respectively.
25. 3II was selected for both the primary binding screening assay and the functional cell-based assay.
26. 50 calculations in dose-response experiments, sigmoid non-linear regressions were performed.