Synthesis and evaluation of a series of novel 2-[(4- chlorophenoxy)methyl]benzimidazoles as selective neuropeptide Y Y1 receptor antagonists

Journal of Medicinal Chemistry

Volumn 41, Issue 15, 1998, Pages 2709-2719

  Zarrinmayeh, Hamideh ^a   Nunes, Anne M ^a   Ornstein, Paul L ^a   Zimmerman, Dennis M ^a   Arnold, M Brian ^a   Schober, Douglas A ^a   Gackenheimer, Susan L ^a   Bruns, Robert F ^a   Hipskind, Philip A ^a   Britton, Thomas C ^a   Cantrell, Buddy E ^a   Gehlert, Donald R ^a  

^a ELI LILLY AND COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 [3 (3 PIPERIDINYL)BUTYL] 2 [(4 CHLOROPHENOXY)METHYL]BENZIMIDAZOLE TRIFLUOROACETATE; 2 [(4 CHLOROPHENOXY)METHYL] 4 HYDROXYBENZIMIDAZOLE; BENZIMIDAZOLE DERIVATIVE; BIS[1 [3 (3 PIPERIDINYL)PROPYL] 2 [(4 CHLOROPHENOXY)METHYL] 4 [[3 (1 PIPERIDINYL)PROPYL]OXY]BENZIMIDAZOLE]TRIFLUOROACETATE; NALPHA (DIPHENYLACETYL) N (4 HYDROXYBENZYL) DEXTRO ARGININAMIDE; NEUROPEPTIDE Y; NEUROPEPTIDE Y RECEPTOR ANTAGONIST; NEUROPEPTIDE Y1 RECEPTOR; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; CHO CELL; CONTROLLED STUDY; DRUG ANTAGONISM; DRUG RECEPTOR BINDING; DRUG SELECTIVITY; DRUG SYNTHESIS; NONHUMAN; RECEPTOR BLOCKING; STRUCTURE ACTIVITY RELATION;

BENZIMIDAZOLES; CELL LINE; CYCLIC AMP; HUMANS; RECEPTORS, NEUROPEPTIDE Y; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 14444272751     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm9706630     Document Type: Article

References (32)

1. Tatemoto, K.; Carlquist, M.; Mutt, V. Neuropeptide Y - a novel brain peptide with structural similarities to peptide YY and pancreatic polypeptide. Nature 1982, 296, 659-660.
2. O'Donohue, T. L.; Chronwall, B. M.; Pruss, R. M.; Mezey, E.; Kiss, J. Z.; Eiden, L. E.; Massari, V. J.; Tessel, R. E.; Pickel, V. M.; DiMaggio, D. A.; Hotchkiss, A. J.; Crowly, W. R.; Zukowska-Grojec, Z. Neuropeptide Y and peptide YY neuronal and endocrine systems. Peptides 1985, 6, 755-768.
3. Tatemoto, K.; Mann, M., J.; Shimizu, M. Synthesis of receptor antagonists of neuropeptide Y. Proc. Natl. Acad. Sci. U.S.A. 1992, 89, 1174-1178.
4. Stanley, B. G.; Leibowitz, S. F. Neuropeptide Y injected in the paraventricular hypothalamus: a powerful stimulant of feeding behavior. Proc. Natl. Acad. Sci. U.S.A. 1985, 82, 3940-3943.
5. Kalra, S. P.; Dube, M. G.; Fournier, A.; Kalra, P. S. Structure-function analysis of stimulation of food intake by neuropeptide Y: effects of receptor agonists. Physiol. Behav. 1992, 50, 5-9.
6. Beck, B.; Stricker-Krongrad, A.; Nicolas, J.-P.; Burlet, C. Chronic and continuous Intracerebroventricular infusion of neuropeptide Y in Long-Evans rats mimics the feeding behavior of obese Zucker rats. Int. J. Obesity 1991, 16, 295-302.
7. Boublik, J. H.; Scott, N. A.; Brown, M. R.; Rivier, J. E. Synthesis and hypertensive activity of neuropeptide Y fragments and analogues with modified N-or C-termini or D-substitutions. J. Med. Chem. 1989, 32, 597-601.
8. Chalmers, J.; Morris, M.; Kapoor, V.; Cain, M.; Elliot, J.; Russel, A.; Pilowsky, P.; Minson, J.; West, M.; Wing, L. Neuropeptide Y in the sympathetic control of blood pressure in hypertensive subjects. Clin. Exp. Hypertens. 1989, 1, 59-66.
9. Kalra, S. P.; Fuentes, M.; Fournier, A.; Parker, S. L.; Crowly, W. R. Involvement of the Y1 receptor subtype in the regulation of luteinizing hormone secretion by neuropeptide Y in rats. Endocrinology 1992, 130, 3323-3330.
10. Clark, J. T.; Kalra, P. S.; Kalra, S. P. Neuropeptide Y stimulates feeding but inhibits sexual behavior in rats. Endocrinology 1985, 117, 2435-2442.
11. Gehlert, D. R. Subtypes of receptors for neuropeptide Y: implications for the targeting of therapeutics. Life Sci. 1994, 55, 551-562.
12. 125I] peptide YY receptor sites. Neuroscience 1990, 36, 255-283.
13. Gerald, C.; Walker, M. W.; Criscione, L.; Gustafson, E. L.; Batzl-Hartmann, C.; Smith, K. E.; Vaysse, P.; Durkin, M. M.; Laz, T. M.; Linemeyer, D. L.; Schaffhauser, A. O.; Whitebread, S.; Hofbauer, K. G.; Taber, R. I.; Branchek, T. A.; Weinshank, R. L. A receptor subtype involved in neuropeptide-Y-induced food intake. Nature 1996, 382, 168-171.
14. Hu, Y.; Bloomquist, B. T.; Cornfield, L. J.; DeCarr, L. B.; Flores-Riveros, J. R. Friedman, L.; Jiang, P.; Lewis-Higgins, L.; Sadlowski, Y.; Schaefer, J.; Velazquez, N.; McCaleb, M. L. Identification of a novel hypothalamic neuropeptideY receptor associated with feeding behavior. J. Biol. Chem. 1996, 271, 26315-26319.
15. Stanley, B. G.; Magdalin, W.; Seirafi, A.; Nguyen, M. M.; Leibowitz, S. F. Evidence for neuropeptide Y mediation of eating produced by food depreviation and for a varient of Y1 receptor mediating this peptide's effect. Peptides 1992, 13, 581-587.
16. Tatemoto, K. Neuropeptide Y, and its receptor antagonists. Ann. NY Acad. Sci. 1990, 611, 1-6.
17. Dryden, S.; Frankish, H.; Wang, Q.; Williams, G. Neuropeptide Y and energy balance: one way ahead for the treatment of obesity. Eur. J. Clin. Invest. 1994, 24, 293-308.
18. 32]-NPY (27-36) infused into the hypothalamus of the rat. Brain Res. Bull. 1995, 37, 237-245.
19. Schwieler, J. H.; Hjemdahl, P. D-myo-inositol-1,2,6-triphosphate (PP56) antagonizes nonadrenergic sympathetic vasoconstriction: possible involvement of neuropeptide Y. J. Cardiovas. Pharmacol. 1993, 21, 347-352.
20. Doughty, M. B.; Chu, S. S.; Miller, D. W.; Li, K.; Tessel, R. E. Benextramines: a long-lasting neuropeptide Y receptor antagonist. Eur. J. Pharmacol. 1990, 185, 113-114.
21. Doughty, M. B.; Chu, S. S.; Misse, G. A.; Tessel, R. Neuropeptide Y (NPY)functional group mimetic: Design, synthesis, and characterization as NPY receptor antagonists. Bioorg. Med. Chem. Lett. 1992, 2, 1497-1502.
22. Chaurasia, C.; Misse, G.; Tessel, R.; Doughty, M. B. Neuropeptide peptidomimetic antagonists of the neuropeptide Y receptor: Benextramine analogues with selectivity for the peripheral Y2 receptor. J. Med. Chem. 1994, 37, 2242-2248.
23. Serradeil-Le Gal, C.; Valette, G.; Rouby, P. E.; Pellet, A.; Villanova, G.; Foulon, L.; Lepsy, L.; Neliat, G.; Chambon, J. P.; Maffrand, J. P.; Le Fur, G. SR 120107A and SR 120819A: Two potent and selective, orally effective antagonists for NPY Y1 receptors. Neurosci. Abstr. 1994, 20, 907.
24. Serradeil-Le Gal, C.; Valette, G.; Rouby, P.-E.; Pellet, A.; Oury-Donat, F.; Brossard, G.; Lepsy, L.; Marty, E.; Neliat, G.; Cointe P.; Maffrand, J.-P.; Le Fur, G. SR 120819A, An orally active and selective neuropeptide Y Y1 receptor antagonist. FEBS Lett. 1995, 362, 192-196.
25. Rudolf, K.; Eberlein, W.; Engel, W.; Wieland, H. A.; Willira, K. D.; Entzeroth, M.; Wienen, W.; Beck-Sickinger, A. G.; Doods, H. N. The first highly potent and selective nonpeptide neuropeptide-Y Y-1-receptor antagonist-BIBP3226. Eur. J. Pharmacol. 1994, 271, R11-R13.
26. Hipskind, P. A.; Lobb, K. L.; Nixon, J. A.; Britton, T. C.; Bruns, R. F.; Catlow, J.; Diekckman-McGinty, D. K.; Gackenheimer, S. L.; Gitter, B. D.; Iyengar, S.; Schober A.; Simmons, R. M.; Swanson, S.; Zarrinmayeh, H.; Zimmerman D. M.; Gehlert, D. R. Potent and selective 1,2,3-trisubstituted indole NPY Y-1 antagonists. J. Med. Chem. 1997, 40, 3712-3714.
27. Egbertson, M. S.; Chang, C. T.-C.; Duggan, M. E.; Gould, R. J.; Halczenko, W.; Hartman, G. D.; Laswell, W. L.; Lynch, J., Jr.; Lynch, R. J.; Manno, P. D.; Naylor, A. M.; Prugh, J. D.; Ramjit, D. R.; Sitko, G. R.; Smith, R. S.; Turich, L. M.; Zhang, G. Non-peptide fibrinogen receptor antagonists. Optimization of a tyrosine template as a mimic for Arg-Gly-Asp. J. Med. Chem. 1994, 37, 2537-2551.
28. Villalobos, A.; Blake, J. F.; Biggers, C. K.; Butler, T. W.; Chapin, D. S.; Chen, Y. L.; Ives, J. L.; Jones, S. B.; Liston, D. R.; Nagel, A. A.; Nason, D. M.; Nielsen, J. A.; Shalaby, I. A.; White, W. F. Novel benzisoxazole derivatives as potent and selective inhibitors of acetylcholinesterase. J. Med. Chem. 1994, 37, 2721-2734.
29. S = 11.74 min.
30. Gehlert, D. R.; Beavers, L. S.; Johnson, D.; Gackenheimer, S. L.; Schober, D. A.; Gadski, R. A. Expression cloning of a human brain neuropeptide Y Y2 receptor. Mol. Pharmacol. 1996, 26, 224-228.
31. Gordon, E. A.; Kohout, T. A.; Fishman, P. H. Characterization of functional neuropeptide Y receptors in a human neuroblastoma line. J. Neurochem. 1990, 55, 506-513.
32. Alvarez, R. A.; Daniels, D. V. A single column method for the assay of adenylate cyclase. Anal. Biochem. 1990, 187, 98-103.