Novel 1-aminoethyl-3-arylsulfonyl-1H-pyrrolo[2,3-b]pyridines are potent 5-HT6 agonists

Bioorganic and Medicinal Chemistry

Volumn 17, Issue 14, 2009, Pages 5153-5163

  Bernotas, Ronald C ^a   Lenicek, Steven ^a   Antane, Schuyler ^a   Cole, Derek C ^b   Harrison, Boyd L ^a   Robichaud, Albert J ^a   Zhang, Guo Ming ^a   Smith, Deborah ^a   Platt, Brian ^a   Lin, Qian ^a   Li, Ping ^a   Coupet, Joseph ^a   Rosenzweig Lipson, Sharon ^a   Beyer, Chad E ^a   Schechter, Lee E ^a  

^a PFIZER INC   (United States)

^b WYETH RESEARCH   (United States)

Author keywords

5 Hydroxytryptamine 6 receptor; 7 Azaindole; Adenylyl cyclase assay; Agonist; Binding; Pyrrolo 2,3 b pyridine; Serotonin; Sulfone

Indexed keywords

1 (N,N DIMETHYLAMINOETHYL) 3 PHENYLSULFONYL 1H PYRROLO[2,3 B]PYRIDINE; 4 AMINOBUTYRIC ACID; ADENYLATE CYCLASE; DOPAMINE RECEPTOR; GLUTAMIC ACID; N [2 [3 [(3 FLUOROPHENYL)SULFONYL] 1H PYRROLO[2,3 B]PYRIDIN 1 YL]ETHYL] N,N DIETHYLAMINE; PYRROLO[2,3 B]PYRIDINE DERIVATIVE; SEROTONIN 6 RECEPTOR; SEROTONIN RECEPTOR AFFECTING AGENT; UNCLASSIFIED DRUG; WAY 208466;

ANIMAL EXPERIMENT; ANXIETY DISORDER; ARTICLE; BINDING AFFINITY; CONTROLLED STUDY; DOPAMINERGIC SYSTEM; DRINKING BEHAVIOR; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SELECTIVITY; DRUG STRUCTURE; FRONTAL CORTEX; IN VITRO STUDY; IN VIVO STUDY; LIGAND BINDING; NEUROTRANSMISSION; NONHUMAN; OBSESSIVE COMPULSIVE DISORDER; POLYDIPSIA; PROTON NUCLEAR MAGNETIC RESONANCE; RAT; SEROTONINERGIC SYSTEM; STRUCTURE ACTIVITY RELATION;

ANIMALS; CEREBRAL CORTEX; DRINKING BEHAVIOR; GAMMA-AMINOBUTYRIC ACID; GLUTAMIC ACID; HELA CELLS; HUMANS; PROTEIN BINDING; RATS; RECEPTORS, SEROTONIN; SEROTONIN AGONISTS;

RATTUS;

EID: 67650085637     PISSN: 09680896     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmc.2009.05.055     Document Type: Article

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25. 6 receptor were washed with Krebs buffer and incubated at 37 °C in Krebs supplemented with 500 μM IBMX for 5 min at 37 °C. Cells were then stimulated with test compound in the concentration range 0.1-10000 nM for an additional 10 min at 37 °C. Serotonin was also tested to determine the maximal response of endogenous ligand. The agonist potency was determined from the resulting concentration-response curves and the percent efficacy determined relative to serotonin. Antagonist activity was determined by the ability of test compound to block adenylyl cyclase activity in the presence of serotonin. Detailed assay conditions can be found in the supporting information for Ref. 9c.
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27. Full details of the in vivo assays, including the microdialysis and schedule-induce polydipsia, can be found in the supporting information of Ref. 9c.