Discovery of a novel class of bicyclo[3.1.0]hexanylpiperazines as noncompetitive neuropeptide y Y1 antagonists

ACS Medicinal Chemistry Letters

Volumn 3, Issue 3, 2012, Pages 222-226

  Hu, Shuanghua ^a   Huang, Yazhong ^a   Deshpande, Milind ^a   Luo, Guanglin ^a   Bruce, Marc A ^a   Chen, Ling ^a   Mattson, Gail ^a   Iben, Lawrence G ^a   Zhang, Jie ^a   Russell, John W ^a   Clarke, Wendy J ^a   Hogan, John B ^a   Ortiz, Astrid ^a   Flint, Oliver ^a   Henwood, Andrew ^a   Gao, Qi ^a   Antal Zimanyi, Ildiko ^a   Poindexter, Graham S ^a  

^a BRISTOL MYERS SQUIBB   (United States)

Author keywords

bicyclo 3.1.0 hexanylpiperazines; brain penetration; noncompetitive neuropeptide Y Y1 antagonists

Indexed keywords

1 (1ALPHA,3ALPHA,5ALPHA,6BETA) 6 3 ETHOXYPHENYL 3 METHYLBICYCLO[3.1.0]HEXAN 6YL 4 PHENYLPIPERAZINE; APPETITE STIMULANT; BICYCLO[3.1.0]HEXANYLPIPERAZINE; BMS 193885; FENFLURAMINE; NEUROPEPTIDE Y RECEPTOR ANTAGONIST; NEUROPEPTIDE Y1 RECEPTOR; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BRAIN; CONTROLLED STUDY; DRUG BIOAVAILABILITY; DRUG DESIGN; DRUG PENETRATION; DRUG SYNTHESIS; FOOD INTAKE; HUMAN; HUMAN CELL; IC 50; NONHUMAN; PRIORITY JOURNAL; RAT; SPRAGUE DAWLEY RAT;

RATTUS;

EID: 84863258835     PISSN: None     EISSN: 19485875     Source Type: Journal    
DOI: 10.1021/ml200265m     Document Type: Article

References (33)

1. Yulyaningsih, E.; Lei Zhang, L.; Herzog, H.; Sainsbury, A. NPY receptors as potential targets for anti-obesity drug development Br. J. Pharmacol. 2011, 163, 1170-1202
2. Walther, C.; Morl, K.; Beck-Sickinger, A. G. Neuropeptide Y receptors: Ligand binding and trafficking suggest novel approaches in drug development J. Pept. Sci. 2011, 17, 233-246
3. Zimanyi, I. A.; Poindexter, G. NPY-Ergic agents for the treatment of obesity Drug Dev. Res. 2000, 51, 94-111 (Pubitemid 32048448)
4. Sato, N.; Ogino, Y.; Mashiko, S.; Ando, M. Modulation of neuropeptide Y receptors for the treatment of obesity Expert Opin. Ther. Patents 2009, 19, 1401-1415
5. Ishihara, A.; Moriya, M.; Macneil, D. J.; Fukami, T.; Kanatani, A. Neuropeptide Y receptors as targets of obesity treatment Expert Opin. Ther. Patents 2006, 16, 1701-1712 (Pubitemid 46017247)
6. Chao, P.-T.; Yang, L.; Aja, S.; Moran, T. H.; Bi, S. Knockdown of NPY expression in the dorsomedial hypothalamus promotes development of brown adipocytes and prevents diet-induced obesity Cell Metab. 2011, 13, 573-583
7. Nguyen, A. D.; Herzog, H.; Sainsbury, A. Neuropeptide y and peptide YY: Important regulators of energy metabolism Curr. Opin. Endocrinol. Diabetes Obes. 2011, 18, 56-60
8. Parker, E.; Wan Heek, M.; Stamford, A. Neuropeptide Y receptors as targets for antiobesity drug development: Perspective and current status Eur. J. Pharmacol. 2002, 440, 173-187 (Pubitemid 34458022)
9. Chamorro, S.; Della-Zuana, O.; Fauchere, J.-L.; Galizzi, J.-P.; Levens, N. Appetite suppression based on selective inhibition of NPY receptors Int. J. Obes. 2002, 26, 281-298 (Pubitemid 34226153)
10. Guan, X.-M.; Yu, H.; Van der Ploeg, L. H. T. Evidence of altered hypothalamic pro-opiomelanocortin/neuropeptide Y mRNA expression in tubby mice Mol. Brain Res. 1998, 59, 273-279 (Pubitemid 28434510)
11. Kesterson, R. A.; Huszar, D.; Lynch, C. A.; Simerly, R. B.; Cone, R. D. Induction of neuropeptide Y gene expression in the dorsal medial hypothalamic nucleus in two models of the agouti obesity syndrome Mol. Endocrinol. 1997, 11, 630-637 (Pubitemid 27193798)
12. Erickson, J. C.; Hollopeter, G.; Palmiter, R. D. Attenuation of the obesity syndrome of ob/ob mice mice by the loss of neuropeptide Y Science (Washington, DC) 1996, 274, 1704-1707 (Pubitemid 26414900)
13. Zarjevski, N.; Cusin, I.; Vettor, R.; Rohner-Jeanrenaud, F.; Jeanrenaud, B. Chronic intracerebroventricular neuropeptide-Y administration to normal rats mimics hormonal and metabolic changes of obesity Endocrinology 1993, 133, 1753-1758 (Pubitemid 23295205)
14. Lin, E.-J. D.; Zhang, L.; Sainsbury, A.; Herzog, H. Y2, Y4 receptors and obesity Expert Rev. Endocrinol. Metab. 2007, 2, 163-173
15. Ishihara, A.; Tanaka, T.; Kanatani, A.; Fukami, T.; Ihara, M.; Fukuroda, T. A potent neuropeptide Y antagonist, 1229U91, suppressed spontaneous food intake in Zucker fatty rats Am. J. Physiol. 1998, 43, R1500-R1504
16. Kanatani, A.; Ito, J.; Ishihara, A.; Iwaawa, H.; Fukaroda, T.; Fukami, T.; MacNeil, D. J.; Van der Ploeg, L. H. T.; Ihara, M. NPY-induced feeding involves the action of a Y1-like receptor in rodents Regul. Pept. 1998, 75-76, 409-415 (Pubitemid 28477555)
17. Balasubramaniam, A.; Dhawan, V. C.; Mullins, D. E.; Chance, W. T.; Sheriff, S.; Guzzi, M.; Prabhakaran, M.; Parker, E. M. Highly selective and potent neuropeptide Y (NPY) Y1 receptor antagonists based on [Pro(30), Tyr(32), Leu(34)]NPY(28-36)-NH2 (BW1911U90) J. Med. Chem. 2001, 44, 1479-1483
18. Rudolf, K.; Eberlein, W.; Engel, W.; Beck-Sickinger, A. G.; Wittneben, H.; Wieland, H. A.; Doods, H. In Neuropeptide Y and Drug Development; Grundemer, L.; Bloom, S. R., Eds.; Academic Press: San Diego, CA, 1997; pp 175-190.
19. Serradiel-Le Gal, G. In Neuropeptide Y and Drug Development; Grundemer, L.; Bloom, S. R., Eds.; Academic Press: San Diego, CA, 1997; pp 157-174.
20. Zarrinmayeh, H.; Zimmerman, D. M.; Cantrell, B. E.; Schober, D. A.; Bruns, R. F.; Gackenheimer, S. L.; Ornstein, P. L.; Hipskind, P. A.; Britton, T. C.; Gehlert, D. R. Structure-activity relationship of a series of diaminoalkyl substituted benzimidazole as neuropeptide Y Y1 receptor antagonists Bioorg. Med. Chem. Lett. 1999, 9, 647-652 (Pubitemid 29130263)
21. 1 Receptor Antagonists Bioorg. Med. Chem. Lett. 2002, 12, 379-382 (Pubitemid 34113907)
22. Antal-Zimanyi, I.; Bruce, M.; LeBoulluec, K.; Iben, L.; Mattson, G.; McGovern, R.; Hogan, J.; Leahy, C.; Flowers, S.; Stanley, J.; Ortiz, A.; Poundexter, G. Pharmacological characterization and appetite suppressive properties of BMS-193885, a novel and selective neuropeptide Y1 receptor antagonist Eur. J. Pharmacol. 2008, 590, 224-232
23. Colin, P. L.; Romano, D. F.; Francesca, B.; Manuela, B.; Simone, B.; Giovanna, D. F.; Daniele, D.; Alessandro, F.; Damiano, G.; Riccardo, G.; Francesca, P.; Angelo, P.; Giorgio, P.; Domenica, A. P.; Giovanna, R.; Luigi, S. Novel carbazole derivatives as NPY Y1 antagonists Bioorg. Med. Chem. Lett. 2007, 17, 1043-1046
24. Kanatani, A.; Kanno, T.; Ishihara, A.; Hata, M.; Sakuraba, A.; Tanaka, T.; Tsuchiya, Y.; Mase, T.; Fukuroda, T.; Fukami, T.; Ihara, M. The novel neuropeptide Y Y(1) receptor antagonist J-104870: A potent feeding suppressant with oral bioavailability Biochem. Biophys. Res. Commun. 1999, 266, 88-91 (Pubitemid 30028772)
25. Ishihara, A.; Kanatani, A.; Okada, M.; Hidaka, M.; Ianaka, I.; Mashiko, S.; Gomori, A.; Kanno, I.; Hata, M.; Kanesaka, M.; Iominaga, Y.; Sato, N.; Kobayashi, M.; Mural, I.; Watanabe, K.; Ishii, Y.; Fukuroda, I.; Fukami, I.; Ihara, M. Blockade of body weight gain and plasma corticosterone levels in Zucker fatty rats using an orally active neuropeptide Y Y1 antagonist Br. J. Phamacol. 2002, 136, 341-346 (Pubitemid 34620513)
26. Kannoa, T.; Kanatani, A.; Keen, S. L.; Arai-Otsuki, S.; Haga, Y.; Iwama, T.; Ishihara, A.; Sakuraba, A.; Iwaasa, H.; Hirose, M.; Morishima, H.; Fukami, T.; Ihara, M. Different binding sites for the neuropeptide Y Y1 antagonists 1229U91 and J-104870 on human Y1 receptors Peptides 2001, 22, 405-413 (Pubitemid 32250241)
27. Peterson, J. M.; Blum, C. A.; Cai, G.; Hutchison, A. U.S. Patent 5900415, 1999.
28. Allen, D. J.; Brostron, L. R.; Kord, A. S.; Whipple, L. A. WO 9823603, 1998.
29. Tetzlaff, F.; Vilsmaier, E.; Schlag, W.-R. Functionalized chloroenamines in aminocyclopropane synthesisî - ̧VI. Chlorotetrahydropyridines as a basis for the synthesis of 3-azabicyclo[3.1.0.]hexane derivatives Tetrahedron 1990, 46, 8117-8130
30. Full crystallographic data have been deposited to the Cambridge Crystallographic Data Center (CCDC reference number 865396). Copies of the data can be obtained free of charge via the internet at http://www.ccdc.cam.ac.uk.
31. Dambach, D. M.; Andrews, B. A; Moulin, F. New technologies and screening strategies for hepatotoxicity: Use of in vitro models Toxicol. Pathol. 2005, 33, 17-26 (Pubitemid 40216800)
32. Zimmerman, H. J. Hepatotoxicity, 2 nd ed.; Lippincott Williams & Wilkins: Philadelphia, PA, 1999; pp 3-10.
33. Maron, D. M.; Ames, B. N. Revised methods for the Salmonella mutagenicity test Mutat. Res. 1983, 113, 173-215 (Pubitemid 13120319)