Discovery of a selective S1P1 receptor agonist efficacious at low oral dose and devoid of effects on heart rate

ACS Medicinal Chemistry Letters

Volumn 2, Issue 6, 2011, Pages 444-449

  Demont, Emmanuel H ^a   Andrews, Benjamin I ^a   Bit, Rino A ^a   Campbell, Colin A ^a   Cooke, Jason W B ^a   Deeks, Nigel ^a   Desai, Sapna ^a   Dowell, Simon J ^a   Gaskin, Pam ^a   Gray, James R J ^a   Haynes, Andrea ^a   Holmes, Duncan S ^a   Kumar, Umesh ^a   Morse, Mary A ^a   Osborne, Greg J ^a   Panchal, Terry ^a   Patel, Bela ^a   Perboni, Alcide ^a   Taylor, Simon ^a   Watson, Robert ^a   Witherington, Jason ^a   Willis, Robert ^a   more..

^a GLAXOSMITHKLINE   (United Kingdom)

Author keywords

agonism; bradycardia; Fingolimod; lymphopenia; multiple sclerosis; S1P

Indexed keywords

3 [6 [5 [3 CYANO 4 [(1 METHYLETHYL)OXY]PHENYL] 1,2,4 OXADIAZOL 3 YL] 5 METHYL 3,4 DIHYDRO 2(1H) ISOQUINOLINYL]PROPANOATE; ANTIRHEUMATIC AGENT; COLLAGEN; FINGOLIMOD; SPHINGOSINE 1 PHOSPHATE RECEPTOR; SPHINGOSINE 1 PHOSPHATE RECEPTOR AGONIST; UNCLASSIFIED DRUG;

ARTHRITIS; ARTICLE; BRADYCARDIA; DISTRIBUTION VOLUME; DRUG BIOAVAILABILITY; DRUG DISTRIBUTION; DRUG HALF LIFE; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SELECTIVITY; DRUG SYNTHESIS; HEART RATE; HUMAN; HYPERTENSION; MOUSE; MULTIPLE SCLEROSIS; NONHUMAN; PRIORITY JOURNAL; RAT; STRUCTURE ACTIVITY RELATION; TELEMETRY;

RATTUS;

EID: 79959260570     PISSN: None     EISSN: 19485875     Source Type: Journal    
DOI: 10.1021/ml2000214     Document Type: Article

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33. The exposure of 20 depends linearly of the dose given between 0.1 and 300 mg/kg po in rats.
34. 50 = 6.8 ± 0.16, 77% of maximum response, n = 6). See the experimental part for assay protocols.