Selective modulation of Gq/Gs pathways by naphtho pyrano pyrimidines as antagonists of the neuropeptide S receptor

ACS Chemical Neuroscience

Volumn 1, Issue 8, 2010, Pages 559-574

  McCoy, Joshua G ^a   Marugan, Juan J ^a   Liu, Ke ^a   Zheng, Wei ^a   Southall, Noel ^a   Huang, Wenwei ^a   Heilig, Markus ^b   Austin, Christopher P ^a  

^a NATIONAL HUMAN GENOME RESEARCH INSTITUTE   (United States)

^b NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM   (United States)

Author keywords

addiction disorders; homogeneous time resolved fluorescence; naphtho pyrano pyrimidines; neuropeptide S radiolabel displacement assay; Neuropeptide S receptor antagonist; sleepdisorders

Indexed keywords

10 (2 MORPHOLINOETHYL) 12 (3 METHOXYPHENYL) 12H NAPHTHO[1',2':5,6]PYRANO[2,3 D]PYRIMIDIN 11 IMINE; 10 (2 MORPHOLINOETHYL) 12 (3,4 DIMETHOXYPHENYL) 12H NAPHTHO[1',2':5,6]PYRANO[2,3 D]PYRIMIDIN 11 IMINE; 10 (2 MORPHOLINOETHYL) 12 (4 METHOXYPHENYL) 12H NAPHTHO[1',2':5,6]PYRANO[2,3 D]PYRIMIDIN 11 IMINE; 10 (2 MORPHOLINOETHYL) 12 PHENYL 12H NAPHTHO[1',2':5,6]PYRANO[2,3 D]PYRIMIDIN 11 IMINE; 10 BENZYL 12 (3,4 DIMETHOXYPHENYL) 12H NAPHTHO[1',2':5,6]PYRANO[2,3 D] PYRIMIDIN 11 IMINE; 10 BENZYL 12 PHENYL 12H NAPHTHO[1',2':5,6]PYRANO[2,3 D] PYRIMIDIN 11 IMINE; 10 PHENETHYL 12 (3,4 DIMETHOXYPHENYL) 12H NAPHTHO[1',2':5,6]PYRANO[2,3 D] PYRIMIDIN 11 IMINE; 10 PHENETHYL 12 PHENYL 12H NAPHTHO[1',2':5,6]PYRANO[2,3 D] PYRIMIDIN 11 IMINE; 10 PHENYL 12 (2 METHOXYPHENYL 12H NAPHTHO[1',2':5,6]PYRANO[2,3 D]PYRIMIDIN 11 IMINE; 10 PHENYL 12 (2,3 DIHYDROBENZO[B][1,4]DIOXIN 6 YL) 12H NAPHTHO[1',2':5,6] PYRANO[2,3 D]PYRIMIDIN 11 IMINE; 10 PHENYL 12 (2,3 DIHYDROBENZOFURAN 5 YL) 12H NAPHTHO[1',2':5,6] PYRANO[2,3 D]PYRIMIDIN 11 IMINE; 10 PHENYL 12 (2,3 DIMETHOXYPHENYL) 12H NAPHTHO[1',2':5,6] PYRANO[2,3 D]PYRIMIDIN 11 IMINE; 10 PHENYL 12 (3 METHOXYPHENYL 12H NAPHTHO[1',2':5,6]PYRANO[2,3 D]PYRIMIDIN 11 IMINE; 10 PHENYL 12 (3,4 DIETHOXYPHENYL) 12H NAPHTHO[1',2':5,6] PYRANO[2,3 D]PYRIMIDIN 11 IMINE; 10 PHENYL 12 (BENZO[D][1,3]DIOXOL) 12H NAPHTHO[1',2':5,6] PYRANO[2,3 D]PYRIMIDIN 11 IMINE; 10 PHENYL 12 PHENYL 12H NAPHTHO[1',2':5,6]PYRANO[2,3 D]PYRIMIDIN 11 IMINE; 10 PHENYLBUTYL 12 PHENYL 12H NAPHTHO[1',2':5,6]PYRANO[2,3 D] PYRIMIDIN 11 IMINE; 10 PHENYLPROPYL 12 (3,4 DIMETHOXYPHENYL) 12H NAPHTHO[1',2':5,6]PYRANO[2,3 D] PYRIMIDIN 11 IMINE; 10 PHENYLPROPYL 12 PHENYL 12H NAPHTHO[1',2':5,6]PYRANO[2,3 D] PYRIMIDIN 11 IMINE; AGENTS INTERACTING WITH TRANSMITTER, HORMONE OR DRUG RECEPTORS; CYCLIC AMP; GQ PROTEIN; GUANINE NUCLEOTIDE BINDING PROTEIN; NAPHTHOPYRANOPYRIMIDINE; NEUROPEPTIDE RECEPTOR; NEUROPEPTIDE S RECEPTOR; NEUROPEPTIDE S RECEPTOR ANTAGONIST; PYRIMIDINE DERIVATIVE; RGS PROTEIN; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ANIMAL CELL; ARTICLE; CALCIUM SIGNALING; DRUG SYNTHESIS; NEUROMODULATION; NONHUMAN; PRIORITY JOURNAL; SIGNAL TRANSDUCTION; STRUCTURE ACTIVITY RELATION;

EID: 77955895428     PISSN: None     EISSN: 19487193     Source Type: Journal    
DOI: 10.1021/cn100040h     Document Type: Article

References (16)

1. Laitinen, T., Polvi, A., Rydman, P., Vendelin, J., Pulkkinen, V., Salmikangas, P., M'kel', S., Rehn, M., Pirskanen, A., Rautanen, A., Zucchelli, M., Gullst'n, H., Leino, M., Alenius, H., Pet'ys, T., Haahtela, T., Laitinen, A., Laprise, C., Hudson, T. J., Laitinen, L. A., and Kere, J. (2004) Characterization of a common susceptibility locus for asthma-related traits Science 304, 300-304
2. Xu, Y.-L., Reinscheid, R.-K., Huitron-Resendiz, S., Clark, S.-D., Wang, Z., Lin, S.-H., Brucher, F.-A., Zeng, J., Ly, N.-K., Henriksen, S.-J., de Lecea, L., and Civelli, O. (2004) Neuropeptide S: A neuropeptide promoting arousal and anxiolytic-like effects Neuron 43 (4) 487-497
3. Reinscheid, R.-K. and Xu, Y.-L. (2005) Neuropeptide S as a novel arousal promoting peptide transmitter FEBS J. 272 (22) 5689-5693
4. Okamura, N. and Reinscheid, R.-K. (2007) Neuropeptide S: a novel modulator of stress and arousal Stress 10 (3) 221-226
5. Leonard, S.-K., Dwyer, J.-M., Sukoff Rizzo, S.-J., Platt, B., Logue, S.-F., Neal, S.-J., Malberg, J.-E., Beyer, C.-E., Schechter, L.-E., Rosenzweig-Lipson, S., and Ring, R.-H. (2008) Pharmacology of neuropeptide S in mice: therapeutic relevance to anxiety disorders Psychopharmacology 197 (4) 601-611
6. Rizzi, A., Vergura, R., Marzola, G., Ruzza, C., Guerrini, R., Salvadori, S., Regoli, D., and Calo, G. (2008) Neuropeptide S is a stimulatory anxiolytic agent: a behavioural study in mice Br. J. Pharmacol. 154 (2) 471-479
7. Pa'eda, C., Huitron-Resendiz, S., Frago, L.-M., Chowen, J.-A., Picetti, R., de Lecea, L., and Roberts, A.-J. (2009) Neuropeptide S reinstates cocaine-seeking behavior and increases locomotor activity through corticotropin-releasing factor receptor 1 in mice J. Neurosci. 29 (13) 4155-4161
8. Guerrini, R., Camarda, V., Trapella, C., Calo, G., Rizzi, A., Ruzza, C., Fiorini, S., Marzola, E., Reinscheid, R.-K., Regoli, D., and Salvadori, S. (2009) Synthesis and biological activity of human neuropeptide S analogues modified in position 5: Identification of potent and pure neuropeptide S receptor antagonists J. Med. Chem. 52 (2) 524-529
9. Camarda, V., Rizzi, A., Ruzza, C., Zucchini, S., Marzola, G., Marzola, E., Guerrini, R., Salvadori, S., Reinscheid, R.-K., Regoli, D., and Calo, G. (2009) In vitro and in vivo pharmacological characterization of the neuropeptide S receptor antagonist [D-Cys(tBu)5]neuropeptide S J. Pharmacol. Exp. Ther. 328 (2) 549-555
10. Guerrini, R., Camarda, V., Trapella, C., Calo, G., Rizzi, A., Ruzza, C., Fiorini, S., Marzola, E., Reinscheid, R.-K., Regoli, D., and Salvadori, S. (2009) Further studies at neuropeptide S position 5: Discovery of novel neuropeptide S receptor antagonists J. Med. Chem. 52 (13) 4068-4071
11. Okamura, N., Habay, S.-A., Zeng, J., Chamberlin, A.-R., and Reinscheid, R.-K. (2008) Synthesis and pharmacological in vitro and in vivo profile of 3-oxo-1,1-diphenyl-tetrahydro-oxazolo[3,4-a]pyrazine-7-carboxylic acid 4-fluoro-benzylamide (SHA 68), a selective antagonist of the neuropeptide S receptor J. Pharmacol. Exp. Ther. 325 (3) 893-901
12. Zhang, Y., Gilmour, B.-P., Navarro, H.-A., and Runyon, S.-P. (2008) Identifying structural features on 1,1-diphenylhexahydrooxazolo[3,4-a]pyrazin-3- ones critical for neuropeptide S antagonist activity Bioorg. Med. Chem. Lett. 18 (14) 4064-4067
13. Melamed, J.-Y., Zartman, A.-E., Kett, N., Cox, C., Gotter, A., Uebele, V.-N., Reiss, D.-R., Doran, S.-M., Garson, S.-L., Tannenbaum, P., Condra, C., Fandozzi, C., Lubbers, L., Rowe, B., McGaughey, G., Sanders, J., Renger, J., Hartman, G.-D., Bilodeau, M.-T., and Trotter, B.-W. (2009) Synthesis and Evaluation of Structurally Diverse Neuropeptide S Receptor (NPSR) Antagonists, in Abstracts of Papers, 238th ACS National Meeting, Aug 16?20, 2009, Washington, DC.
14. A paper with the description of our qHTS methodology and the pharmacology of our series is in preparation.
15. Sato, S., Shintani, Y., Miyajima, N., and Yoshimura, K. (2002) Novel G protein-coupled receptor protein and DNA thereof, World Patent Application WO 02/31145 A1.
16. Liu, K., Southall, N., Titus, S. A., Inglese, J., Eskay, R. L., Shinn, P., Austin, C. P., Heilig, M. A., and Zheng, W. (2010) A multiplex calcium assay for identification of GPCR agonists and antagonists. Assay Drug Dev. Technol., in press.