Toward potent ghrelin receptor ligands based on trisubstituted 1,2,4-triazole structure. 2. Synthesis and pharmacological in vitro and in vivo evaluations

Journal of Medicinal Chemistry

Volumn 50, Issue 23, 2007, Pages 5790-5806

  Moulin, Aline ^a   Demange, Luc ^a   Bergé, Gilbert ^a   Gagne, Didier ^a   Ryan, Joanne ^a   Mousseaux, Delphine ^b   Heitz, Annie ^c   Perrissoud, Daniel ^d   Locatelli, Vittorio ^d   Torsello, Antonio ^a   Galleyrand, Jean Claude ^a   Fehrentz, Jean Alain ^a   Martinez, Jean ^a  

^a UNIVERSITÉ DE MONTPELLIER   (France)

^b CENTRE DE BIOCHIMIE STRUCTURALE   (France)

^c Zentaris GmbH   (Germany)

^d UNIVERSITY OF MILANO BICOCCA   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

1,2,4 TRIAZOLE DERIVATIVE; 2 METHYLALANYL DEXTRO TRYPTOPHAN 1 FORMAMIDO 2 (3 INDOLYL)ETHYLAMIDE; CAPROMORELIN; GHRELIN RECEPTOR; GROWTH HORMONE; HEXARELIN; HORMONE RECEPTOR; IBUTAMOREN; JMV 2894; JMV 2959; JMV 3021; JMV 3031; LY 444711; N [1 [4 (4 METHOXYBENZYL) 5 PHENETHYL 4H 1,2,4 TRIAZOL 3 YL] 2 (1H INDOL 3 YL)ETHYL] 2 AMINOACETAMIDE; N [1 [5 [(1H INDOL 3 YL)METHYL] 4 (4 METHOXYBENZYL) 4H 1,2,4 TRIAZOL 3 YL] 2 (1H INDOL 3 YL)ETHYL]PIPERAZINE 2 CARBOXAMIDE; N [1 [5 [2 (1H INDOL 3 YL)ETHYL] 4 (2,4 DIMETHOXYBENZYL) 4H 1,2,4 TRIAZOL 3 YL] 2 (1H INDOL 3 YL)ETHYL]PIPERIDINE 4 CARBOXAMIDE; N [1 [5 [2 (1H INDOL 3 YL)ETHYL] 4 (4 METHOXYBENZYL) 4H 1,2,4 TRIAZOL 3 YL] 2 (1H INDOL 3 YL)ETHYL]PYRROLIDINE 2 CARBOXAMIDE; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; CALCIUM MOBILIZATION; CONTROLLED STUDY; DRUG EFFECT; DRUG SCREENING; DRUG STRUCTURE; FOOD INTAKE; GROWTH HORMONE RELEASE; IN VITRO STUDY; IN VIVO STUDY; MALE; NONHUMAN; RAT;

ANIMALS; CALCIUM; CELL LINE; CRICETINAE; EATING; GROWTH HORMONE; HUMANS; LIGANDS; MALE; OLIGOPEPTIDES; RADIOLIGAND ASSAY; RATS; RATS, SPRAGUE-DAWLEY; RECEPTORS, GHRELIN; RECOMBINANT PROTEINS; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; TRIAZOLES;

EID: 36148975300     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm0704550     Document Type: Article

References (11)

1. Bowers, C. Y.; Chang, J.; Momany, F.; Folkers, K. Effects of the Enkephalins and Enkephalin Analogs on Release of Pituitary Hormones in Vitro. In Molecular Endocrinology; Macintyne, I., Eds.; Elsevier: Amsterdam, The Netherlands, 1977; pp 287-292.
2. Howard, A. D.; Feighner, S. D.; Cully, D. F.; Arena, J. P.; Liberator, P. A.; Rosenblum, C. I.; Hamelin, M. J.; Hreniuk, D. L.; Palyha, O. C.; Anderson, J.; Paress, P. S.; Diaz, C.; Chou, M.; Liu, K.; Mckee, K. K.; Pong, S. S, Chaung, L. Y.; Elbrecht, A.; Heavens, R.; Rigby, M.; Sirinathsinghji, D. J. S.; Dean, D. C.; Melillo, D. G.; Patchett, A. A.; Nargund, R.; Griffin, P. R.; DeMartino, J. A.; Gupta, S. K.; Schaeffer, J. M.; Smith, R. G.; Van Der Ploeg, L. H. T. A receptor in pituitary and hypothalamus that functions in growth hormone release. Science 1996, 273, 974-977.
3. Kojima, M.; Hosoda, H.; Date, Y.; Nakazato, M.; Matsuo, H.; Kangawa, K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 1999, 402, 656-660.
4. Demange, L.; Boeglin, D.; Moulin, A.; Mousseaux, D.; Ryan, J.; Bergé, G.; Gagne, D.; Heitz, A.; Perrissoud, D.; Locatelli, V.; Torsello, A.; Galleyrand, J.-C.; Fehrentz, J.-A.; Martinez, J. Synthesis and pharmacological in vitro and in vivo evaluations of novel triazole derivatives as ligands of the ghrelin receptor. 1. J. Med. Chem. 2007, 50, 1939-1957.
5. Seyler, D. E.; Dodge, J. A.; Osborne, J. J.; Cox, K. L.; Viswanath, D.; Wilmot, A. F.; Keaton, M. J.; Heiman, M. L.; Bryant, H. U.; Cutler, G. B., Jr. Effect of growth hormone secretagogue LY444711 on IGF-1, growth hormone, and cortisol levels in beagle dogs after one and seven daily oral doses. Drug Dev. Res. 2000, 49, 260-265.
6. Patchett, A. A.; Nargund, R. P.; Tata, J. R.; Chen, M. H.; Barakat, K. J.; Johnston, D. B.; Cheng, K.; Chan, W. W.; Butler, B.; Hickey, G.; Jacks, T.; Schleim, K.; Pong, S. S.; Chaung, L. Y. P.; Chen, H. Y.; Frazier, E.; Leung, K. H.; Chiu, S. H. L.; Smith, R. G. Design and biological activities of L-163,191 (MK-0677): a potent, orally active growth hormone secretagogue. Proc. Natl. Acad. Sci. U.S.A. 1995, 92, 7001-7005.
7. Pan, L. C.; Carpino, P. A.; Lefker, B. A.; Ragan, J. A.; Toler, S. M.; Pettersen, J. C.; Nettleton, D. O.; Ng, O.; Pirie, C. M.; Chidsey-Frink, K.; Lu, B.; Nickerson, D. F.; Tess, D. A.; Mullins, M. A.; MacLean, D. B.; Da Silva-Jardine, P. A.; Thompson, D. D. Preclinical pharmacology of CP-424,391, an orally active pyrazolidinone-piperidine growth hormone secretagogue. Endocrine 2001, 14, 121-132.
8. Guerlavais, V.; Boeglin, D.; Mousseaux, D.; Oiry, C.; Heitz, A.; Deghenghi, R.; Locatelli, V.; Torsello, A.; Ghe, C.; Catapano, F.; Muccioli, G.; Galleyrand, J. C.; Fehrentz, J. A.; Martinez, J. New active series of growth hormone secretagogues. J. Med. Chem. 2003, 46, 1191-203.
9. Broglio, F.; Boutignon, F.; Benso, A.; Gottero, C.; Prodam, F.; Arvat, E.; Ghe, C.; Catapano, F.; Torsello, A.; Locatelli, V.; Muccioli, G.; Boeglin, D.; Guerlavais, V.; Fehrentz, J. A.; Martinez, J.; Ghigo, E.; Deghenghi, R. EP1572: a novel peptido-mimetic GH secretagogue with potent and selective GH-releasing activity in man. J. Endocrinol. Invest. 2002, 8, RC26-RC28.
10. Piccoli, F.; Degen, L.; MacLean, C.; Peter, S.; Baselgia, L.; Larsen, F.; Beglinger, C.; Drewe, J. Pharmacokinetics and pharmacodynamic effects of an oral ghrelin agonist in healthy subjects. J. Clin. Endocrinol. Metab. 2007, 92, 1814-1820.
11. Holst, B.; Mokrosinski, J.; Lang, M.; Brandt, E.; Nygaard, R.; Frimurer, T. M.; Beck-Sickinger, A.; Schwartz, T. W. Identification of an efficacy switch region in the ghrelin receptor responsible for interchange between agonism and inverse agonism. J. Biol. Chem. 2007, 282, 15799-15811.