Discovery of the first potent and selective small molecule opioid receptor-like (ORL1) antagonist: 1-[(3R,4R)-1-cyclooctylmethyl-3- hydroxymethyl-4-piperidyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one (J- 113397)

Journal of Medicinal Chemistry

Volumn 42, Issue 25, 1999, Pages 5061-5063

  Kawamoto, Hiroshi ^a   Ozaki, Satoshi ^a   Itoh, Yoshiki ^a   Miyaji, Mitsuru ^a   Arai, Sachie ^a   Nakashima, Hiroshi ^a   Kato, Tetsuya ^a   Ohta, Hisashi ^a   Iwasawa, Yoshikazu ^a  

^a BANYU PHARMACEUTICAL CO LTD   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

1 (1 CYCLOOCTYLMETHYL 3 HYDROXYMETHYL 4 PIPERIDYL) 3 ETHYL 1,3 DIHYDRO 2H BENZIMIDAZOL 2 ONE; BENZIMIDAZOLE DERIVATIVE; OPIATE ANTAGONIST; OPIATE RECEPTOR; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; CONTROLLED STUDY; DRUG RECEPTOR BINDING; DRUG STRUCTURE; LETTER; MOLECULAR CLONING; MOUSE; NONHUMAN; PAIN; PAIN RECEPTOR; PROTEIN EXPRESSION;

ANIMALS; BENZIMIDAZOLES; HUMANS; PIPERIDINES; RECEPTORS, OPIOID; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0033576679     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm990517p     Document Type: Letter

References (27)

1. (a) Mollereaau, C.; Parmentier, M.; Mailleux, P.; Butour, J.; Moisand, C.; Chalon, P.; Caput, D.; Vassart, G.; Meunier, J.-C. ORL1, a novel member of the opioid receptor family Cloning, functional expression and localization. FEBS Lett. 1994, 341, 33-38.
2. (b) Fukuda, K.; Kato, S.; Mori, K.; Nishi, M.; Takeshima, H.; Iwabe, N.; Miyata, T.; Houtani, T.; Sugimoto, T. cDNA cloning and regional distribution of a novel member of the opioid receptor family. FEBS Lett. 1994, 343, 42-46.
3. (c) Chen, Y.; Fan, Y.; Liu, J.; Mestek, A.; Tian, M.; Kozak, C. A.; Yu, L. Molecular cloning, tissue distribution and chromosomal localization of a novel member of the opioid receptor gene family. FEBS Lett. 1994, 347, 279-283.
4. (d) Pan, Y.-X.; Cheng, J.; Xu, J.; Rossi, G.; Jacobson, E.; Ryan-Moro, J.; Brooks, A. I.; Dean, G. E.; Standifer, K. M.; Pasternak, G. W. Cloning and functional characterization through antisense mapping of a κ3-Related opioid receptor. Mol. Pharmacol. 1995, 47, 1180-1188.
5. (a) Meunier, J.-C.; Mollereau, C.; Toll, L.; Suaudeau, C.; Moisand, C.; Alvinerie, P.; Butour, J.-L.; Guillemot, J.-C.; Ferrara, P.; Monsarrat, B.; Mazargil, H.; Vassart, G.; Parmentier, M.; Costentin, J. Isolation and structure of the endogenous agonist of opioid receptor-like ORL1 receptor. Nature (London) 1995, 377 (6549), 532-535.
6. (b) Reinscheid, R. K.; Nothacher, H.-P.; Bourson, A.; Ardati, A.; Henningsen, R. A.; Bunzow, J. R.; Grady, D. K.; Langen, H.; Monsma, F. J., Jr.; Civelli, O. Orphanin FQ: a neuropeptide that activates an opioidlike G Protein-coupled receptor. Science (Washington, D.C.) 1995, 270 (5237), 792-794.
7. (c) Okuda-Ashitaka, E.; Tachibana, S.; Houtani, T.; Minami, T.; Masu, Y.; Nishi, M.; Takeshima, H.; Sugimoto, T.; Ito, S. Identification and characterization of an endogenous ligand for opioid receptor homologue ROR-C: its involvement in allodynic response to innocuous stimulus. Mol. Brain Res. 1996, 43, 96-104.
8. Meunier, J.-C. Nociceptin/orphanin FQ and the opioid receptor-like ORL1 receptor. Eur. J. Pharmacol. 1997, 340, 1-15.
9. Mogil, J. S.; Grisel, J. E.; Reinscheid, R. K.; Civelli, O.; Belknap, J. K.; Grandy, D. K. Orphanin FQ is a functional anti-opioid peptide. Neuroscience (Oxford) 1996, 75, 333-337.
10. Ueda, H.; Yamaguchi, T.; Tokuyama, S.; Inoue, M.; Nishi, M.; Takeshima H. Partial loss of tolerance liability to morphine analgesia in mice lacking the nociceptin receptor gene. Neuroscience Lett. 1997, 237, 136-138.
11. (a) Manabe, T.; Noda, Y.; Mamiya, T.; Katagiri, H.; Houtani, T.; Nishi, M.; Noda, T.; Takahashi, T.; Sugimoto, T.; Nabeshima, T.; Takeshima, H. Facilitation of long-term potentiation and memory in mice lacking nociceptin receptors. Nature (London) 1998, 394 (6693), 577-581.
12. (b) Sandin, J.; Georgieva, J.; Schött, P. A.; Ögren, S. O.; Terenius, L. Nociceptin/Orphanin FQ microinjected into hippocampus impairs spinal learning in rats. Eur. J. Neurosci. 1997, 9, 194-197.
13. (c) Yu, T.-P.; Fein, J.; Phan, T.; Evans, C. J.; Xie, C.-W. Orphanin FQ inhibits synaptic transmission and long-term potentiation in rat hippocampus. Hippocampus 1997, 7, 88-94.
14. Pomonis, J. D.; Billington, C. J.; Levine, A. S. Orphanin FQ, agonist of orphan opioid receptor ORL1, stimulates feeding in rats. NeuroReport 1996, 8, 369-371.
15. Jenck, F.; Moreau, J.-L.; Martin, J. R.; Kilpatric, G. J.; Reinscheid, R. K.; Monsma, F. J., Jr.; Nothacker, H.-P.; Civelli, O. Orphanin FQ acts as an anxiolytic to attenuate behavioral response to stress. Proc. Natl. Acad. Sci. U.S.A. 1997, 94, 14854-14858.
16. (a) Champion, H. C.; Kadowitz, P. J. Nociceptin, an endogenous ligand for the ORL1 receptor, has novel hypotensive activity in the rat. Life Sci. 1997, 60, 241-245.
17. (b) Gumusel, B.; Hao, Q.; Hyman, A.; Chang, J.-K.; Kapusta, D. R.; Lippton, H. Nociceptin: an endogenous agonist for central opioid like1 (ORL1) receptors possesses systemic vasorelaxant properties. Life Sci. 1997, 60, 141-145.
18. Florin, S.; Suaudeau, C.; Meunier, J.-C.; Costentin, J. Nociceptin stimulates locomotion and exploratory behaviour in mice. Eur. J. Pharmacol. 1996, 317, 9-13.
19. Champion, H. C.; Wang, R.; Hellstrom, W. J. G.; Kadowitz, P. J. Nociceptin, a novel endogenous ligand for the ORL1 receptor, has potent erectile activity in the cat. Am. J. Physiol. 1997, 273 (Endocrinol. Metab. 36), E214-E219.
20. Guerrini, R.; Calo, G.; Rizzi, A.; Bigoni, R.; Bianchi, C.; Salvadori, S.; Regoli, D. A new selective antagonist of the nociceptin receptor. Br. J. Pharmacol. 1998, 123, 163-165.
21. 2 is an agonist of the nociceptin (ORL1) receptor. Eur. J. Pharmacol. 1998, 349, R5-R6.
22. 2 and orphanin FQ/Nociceptin (OFQ/N) produce similar cardiovascular and renal response in conscious rats. J. Pharmacol. Exp. Ther. 1999, 289, 173-180.
23. 2 acts as a partial agonist at ORL1 receptor endogenously expressed in mouse N1E-115 neuroblastoma cells. Neuroreport 1999, 10, 1127-1131.
24. Noda, Y.; Mamiya, T.; Nabeshima, T.; Nishi, M.; Higashioka, M.; Takeshima, H. Loss of antinociception induced by naloxone benzoylhydrazone in nociceptin receptor-knockout mice. J. Biol. Chem. 1998, 273, 18047-18051.
25. (a) Pan, Y.-X.; Cheng, J.; Xu, J.; Rossi, G.; Jacobson, E.; Ryan-Moro, J.; Brooks, A. I.; Dean, G. E.; Standifer, K. M.; Pasternak, G. W. Cloning and functional characterization through antisense mapping of a κ3-related opioid receptor. Mol. Pharmacol. 1995, 47, 1180-1188.
26. (b) Pan, Y.-X.; Xu, J.; Ryan-Moro, J.; Mathis, J.; Horn, J. S. H.; Mei, J.; Pasternak, G. W. Dissociation of affinity and efficacy in KOR-3 chimeras. FEBS Lett. 1996, 395, 207-210.
27. 35S]-GTPγS binding mediated by human muscarinic m1-m4 receptors: Antagonist studies. Br. J. Pharmacol. 1993, 109, 1120-1127.