Bicyclic heteroarylpiperazines as selective brain penetrant 5-HT 6 receptor antagonists

Bioorganic and Medicinal Chemistry Letters

Volumn 15, Issue 21, 2005, Pages 4867-4871

  Ahmed, Mahmood ^a   Briggs, Michael A ^a   Bromidge, Steven M ^a   Buck, Tania ^a   Campbell, Lorraine ^a   Deeks, Nigel J ^a   Garner, Ashley ^a   Gordon, Laurie ^a   Hamprecht, Dieter W ^a   Holland, Vicky ^a   Johnson, Christopher N ^a   Medhurst, Andrew D ^a   Mitchell, Darren J ^a   Moss, Stephen F ^a   Powles, Jenifer ^a   Seal, Jon T ^a   Stean, Tania O ^a   Stemp, Geoffrey ^a   Thompson, Mervyn ^a   Trail, Brenda ^a   Upton, Neil ^a   Winborn, Kim ^a   Witty, David R ^a   more..

^a GLAXOSMITHKLINE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

5 CHLORO N [4 METHOXY 3 (1 PIPERAZINYL)PHENYL] 3 METHYL 2 BENZOTHIOPHENESULFONAMIDE; PIPERAZINE DERIVATIVE; SEROTONIN ANTAGONIST; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ARTICLE; BRAIN; CONTROLLED STUDY; DRUG BIOAVAILABILITY; DRUG PENETRATION; HYDROGEN BOND; NONHUMAN; PROTEIN CONFORMATION; RAT; RECEPTOR AFFINITY;

ADMINISTRATION, ORAL; ANIMALS; BIOLOGICAL AVAILABILITY; BLOOD-BRAIN BARRIER; BRAIN; DOGS; MOLECULAR CONFORMATION; PERMEABILITY; PIPERAZINES; RATS; RECEPTORS, SEROTONIN; SEROTONIN ANTAGONISTS; STRUCTURE-ACTIVITY RELATIONSHIP;

CANIS FAMILIARIS;

EID: 25144505840     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2005.06.107     Document Type: Article

References (17)

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13. 3) 1.50 (9H, s), 3.06 (4H, t, J = 5.0 Hz), 3.65 (4H, t, J = 4.8 Hz), 6.56 (1H, m), 6.83 (1H, d, J = 7.5 Hz), 7.07 (1H, t, J = 7.7 Hz), 7.20 (1H, m), 7.39 (1H, d, J = 7.9 Hz), 8.28 (1H, br s).
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15. CNS penetration was determined at steady state in rat. Compounds were dissolved in 2% (v/v) DMSO in 5% (w/v) dextrose aq and administered at a constant infusion rate over 12 h at a target dose rate of 0.3 mg free base/kg/h. Blood samples were removed during the latter part of the infusion to confirm steady-state blood concentrations. Blood and brain samples were analysed by LC/MS/MS.
16. H 3.4 (4H, br s), 3.6 (4H, br s), 4.8 (2H, br s), 6.9 (1H, d, J = 3.8 Hz), 7.23 (1H, d, J = 8.8 Hz), 7.52 (1H, t, J = 4.0 Hz), 7.65-7.76 (2H, m), 7.82 (1H, d, J = 8.8 Hz), 7.90 (1H, d, J = 8.4 Hz), 7.96 (1H, t, J = 1.8 Hz).
17. appA-B ratio >2, which reverted to unity in the presence of GF120918A.