The identification of a series of novel, soluble non-peptidic neuropeptide y Y2 receptor antagonists

Bioorganic and Medicinal Chemistry Letters

Volumn 20, Issue 24, 2010, Pages 7341-7344

  Lunniss, Gillian E ^a,d   Barnes, Ashley A ^b   Barton, Nick ^b   Biagetti, Matteo ^c   Bianchi, Federica ^c   Blowers, Stephen M ^a   Caberlotto, Laura L ^c   Emmons, Amanda ^b   Holmes, Ian P ^a,d   Montanari, Dino ^c   Norris, Roz ^b   Puckey, Gemma V ^a   Walters, Dewi J ^a   Watson, Steve P ^a   Willis, John ^a  

^a GLAXOSMITHKLINE   (United Kingdom)

^b Molecular Discovery Research   (United Kingdom)

^c Medicines Research Centre   (Italy)

^d MONASH UNIVERSITY   (Australia)

Author keywords

NPY; NPY antagonist; NPY Y2; NPY Y2 antagonist

Indexed keywords

AMIDE; AMINE; BENZHYDRYL AMIDE; NEUROPEPTIDE Y RECEPTOR ANTAGONIST; NEUROPEPTIDE Y2 RECEPTOR; NEUROPEPTIDE Y2 RECEPTOR ANTAGONIST; PIPERIDINE DERIVATIVE; PYRIDINE; PYRIDINE DERIVATIVE; PYRIMIDINE DERIVATIVE; SPIROAMINE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ARTICLE; DRUG BRAIN LEVEL; DRUG IDENTIFICATION; DRUG RECEPTOR BINDING; MAXIMUM PLASMA CONCENTRATION; NONHUMAN; RAT; STRUCTURE ACTIVITY RELATION; TRANQUILIZING ACTIVITY;

AMIDES; AMINES; ANIMALS; CENTRAL NERVOUS SYSTEM; HUMANS; MICROSOMES, LIVER; PYRIMIDINES; RATS; RECEPTORS, NEUROPEPTIDE Y; SPIRO COMPOUNDS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 78449308688     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2010.10.065     Document Type: Article

References (18)

1. M. Hammond IDrugs 4 2001 920
2. T. Kaga, M. Fujimiya, and A. Inui Peptides 22 2001 501
3. T.J. Sajdyk Drug Dev. Res. 65 2005 301
4. N. Sato, Y. Ogino, S. Mashiko, and M. Ando Expert Opin. Ther. Patents 19 2009 1401
5. D. Larhammar, and E. Salaneck Neuropeptides 38 2004 141
6. D. Larhammar, A. Wraith, M.M. Berglund, S.K.S. Holmberg, and I. Lundell Peptides 22 2001 295
7. G.E. Lunniss, A.A. Barnes, N. Barton, M. Biagetti, F. Bianchi, S.B. Blowers, L. Caberlotto, A. Emmons, I.P. Holmes, D. Montanari, R. Norris, D.J. Walters, and S.P. Watson Bioorg. Med. Chem. Lett. 19 2009 4022
8. H. Doods, W. Gaida, H.A. Wieland, H. Dollinger, G. Schnorrenberg, F. Esser, W. Engel, W. Eberlein, and K. Rudolf Eur. J. Pharmacol. 384 1999 R3
9. C.J. Andres, I.A. Zimanyi, M.S. Deshpande, L.G. Iben, K. Grant-Young, G.K. Mattson, and W. Zhai Bioorg. Med. Chem. Lett. 13 2003 2883
10. J.A. Jablonowski, W. Chai, X. Li, D.A. Rudolph, W.V. Murray, M.A. Youngman, S.L. Dax, D. Nepomuceno, P. Bonaventure, T.W. Lovenberg, and N.I. Carruthers Bioorg. Med. Chem. Lett. 14 2004 1239
11. F. Bacchi, A.A. Mathé, P. Jiménez, L. Stasi, R. Arban, P. Gerrard, and L. Caberlotto Peptides 27 2006 3202
12. Brain fractions unbound were determined using equilibrium dialysis in a 96-well format as described in L. Ferrari, V. Crestan, G. Sabattini, F. Vinco, S. Fontana, and A. Gozzi J. Neurosci. Methods 186 2010 143
13. J. Watson, S. Wright, A. Lucas, K.L. Clarke, J. Viggers, S. Cheetham, P. Jeffrey, R. Porter, and K.D. Read Drug Metab. Dispos. 37 2009 753
14. i) 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 four or more experiments.
15. 1H NMR spectroscopy and LC-MS.
16. i) against rat NPY Y2 was determined in a human embryonic kidney (HEK) cell line transiently expressing the receptor, using a 384 well GTPγ35S assay.
17. i) against human NPY Y1 was determined in a Chinese hamster ovarian (CHO) cell line stably expressing the receptor, using a 384 well GTPγ35S assay.
18. i) at the human NPY Y5 receptor stably expressed in HEK293 cells was assessed using FLIPR/Ca2+ methodology in a 384-well format.