The identification and optimisation of novel and selective diamide neuropeptide Y Y2 receptor antagonists

Bioorganic and Medicinal Chemistry Letters

Volumn 19, Issue 15, 2009, Pages 4022-4025

  Lunniss, Gillian E ^a   Barnes, Ashley A ^b   Barton, Nick ^b   Biagetti, Matteo ^c   Bianchi, Federica ^c   Blowers, Stephen M ^a   Caberlotto, Laura ^c   Emmons, Amanda ^b   Holmes, Ian P ^a   Montanari, Dino ^c   Norris, Ros ^b   Walters, Dewi J ^a   Watson, Steve P ^a  

^a GLAXOSMITHKLINE   (United Kingdom)

^b Molecular Discovery Research   (United Kingdom)

^c Neurosciences Centre of Excellence for Drug Discovery   (Italy)

Author keywords

BIIE0246; NPY; NPY antagonist; NPY Y2; NPY Y2 antagonist

Indexed keywords

DIAMIDE; NEUROPEPTIDE Y RECEPTOR ANTAGONIST; NEUROPEPTIDE Y Y2 RECEPTOR ANTAGONIST; UNCLASSIFIED DRUG;

ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DRUG IDENTIFICATION; DRUG POTENCY; DRUG SELECTIVITY; HIGH THROUGHPUT SCREENING; HUMAN; IN VITRO STUDY; NONHUMAN; RAT; STRUCTURE ACTIVITY RELATION;

AMIDES; ANIMALS; ARGININE; BENZAZEPINES; CHEMISTRY, ORGANIC; CHEMISTRY, PHARMACEUTICAL; DRUG DESIGN; HUMANS; INHIBITORY CONCENTRATION 50; MODELS, CHEMICAL; PEPTIDE FRAGMENTS; PROTEIN BINDING; RATS; RECEPTORS, NEUROPEPTIDE Y; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 67649987120     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2009.06.035     Document Type: Article

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14. The functional activity (fpki) against human NPY Y2 was determined in a human neuroblastoma cell line (KAN-TS) which natively expresses NPY Y2, using a 384 well GTPγS35 assay, values quoted were a mean of 4 or more expts.
15. The functional activity (fpki) against rat NPY Y2 was determined in a human embryonic kidney (HEK) cell line transiently expressing the receptor, using a 384 well GTPγS35 assay.
16. 35S assay.
17. The functional activity (fpki) at the human NPY Y5 receptor stably expressed in HEK293 cells was assessed using FLIPR/Ca2+ methodology in a 384 well format.
18. Aqueous solubility was measured via Chemiluminescent Nitrogen Detection (CLND).
19. 3) δ: 1.6 (s, 6H), 2.9 (m,2H), 3.1 (m, 2H), 3.3 (m, 2H), 3.9 (s, 3H), 3.9 (m, 2H), 7.1 (d, 1H), 7.2 (m, 1H), 7.3-7.4 (m, 5H), 7.5 (m,1H), 7.6 (s, 1H), 7.6 (m,1H), 8.2 (d, 1H).