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Non-peptidic δ opioid receptor agonists and antagonists (2000 – 2012)

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Pages 1181-1208 | Published online: 27 May 2013

Bibliography

  • Nagase H, Fujii H. Opioids in preclinical trials. Top Curr Chem 2011;299:29-62
  • Dondio G, Ronzoni S, Petrillo P. Non-peptide delta opioid agonists and antagonists. Exp Opin Ther Patent 1997;7:1075-98
  • Dondio G, Ronzoni S, Petrillo P. Non-peptide delta opioid agonists and antagonists (Part II). Exp Opin Ther Patent 1999;9:353-74
  • Portoghese PS, Sultanat M, Nagase H, Takernori AE. Application of the message-address concept in the design of highly potent and selective non-peptide delta opioid receptor antagonists. J Med Chem 1988;31:281-2
  • Sofuoglu M, Portoghese PS, Takemori AE. Differential antagonism of delta opioid agonists by naltrindole and its benzofuran analog (NTB) in mice: evidence for delta opioid receptor subtypes. J Pharmacol Ther Exp 1991;257:676-80
  • Portoghese PS, Sultana M, Nagase H, Takemori AE. A highly selective delta1-opioid receptor antagonist: 7-benzylidenenaltrexone. Eur J Pharmacol 1992;218:195-6
  • Dondio G, Ronzoni S, Eggleston DS, et al. Discovery of a novel class of substituted pyrrolooctahydroisoquinolines as potent and selective delta opioid agonists, based on an extension of the message-address concept. J Med Chem 1997;40:3192-8
  • Chang KJ, Rigdon GC, Howard JL, McNutt RW. A novel, potent and selective nonpeptidic delta opioid receptor agonist BW373U86. J Pharmacol Ther Exp 1993;267:852-7
  • Calderon SN, Rothman RB, Porreca F, et al. Probes for narcotic receptor mediated phenomena. 19. Synthesis of (+)-4-[(alphaR)-alpha-((2 S,5R)-4-Allyl-2,5-dimethyll-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide (SNC 80): a highly selective, nonpeptide delta opioid receptor agonist. J Med Chem 1994;37:2125-8
  • Su YF, McNutt RW, Chang KJ. Delta-opioid ligands reverse alfentanil-induced respiratory depression but not antinociception. J Pharmacol Ther Exp 1998;287:815-23
  • Nagase H, Yajima Y, Fujii H, et al. The pharmacological profile of delta opioid receptor ligands, (+) and (−) TAN-67 on pain modulation. Life Sci 2001;68:2227-31
  • Toray. Isoquinoline derivatives and uses thereof. JP04275288; 1992
  • Chang KJ, Rigdon GC, Howard JL, McNutt RW. A novel, potent and selective nonpeptidic delta opioid receptor agonist BW373U86. J Pharmacol Ther Exp 1993;267:852-7
  • The Wellcome Foundation. Opioid diarylmethylpiperazines and piperidines. WO93015062; 1993
  • Portoghese PS, Moe ST, Takemori AE. A selective delta1 opioid receptor agonist derived from oxymorphone. Evidence for separate recognition sites for delta1 opioid receptor agonists and antagonists. J Med Chem 1993;36:2572-4
  • Calderona SN, Coop A. SNC 80 and related delta opioid agonists. Curr Pharmaceut Des 2004;10:733-42
  • Bishop MJ, McNutt RW. Benzhydrylpiperazines as nonpeptidic delta opioid receptor ligands. In: Chang KJ, Porreca F, Woods JH, editors. The Delta Receptor. Marcel Decker; New York: 2004. p. 113-38
  • Calderon SN. Nonpeptidic delat (delta) opioid agonists and antagonists of the diarylmethylpiperazine class: what have we learned? Top Curr Chem 2011;299:121-40
  • Watson MJ, Holt JDS, O'Neill SJ, et al. ARD-353 [4-((2R,5S)-4-(R)-(4-diethylcarbamoylphenyl)(3-hydroxyphenyl)methyl)-2,5-dimethylpiperazin-1-ylmethyl)benzoic acid], A novel nonpeptide delta receptor agonist, Reduces myocardial infarct size without central effects. J Pharmacol Exp Ther 2006;316:423-30
  • Liras S, McHardy SF, Allen MP, et al. Biaryl piperidines as potent and selective delta opioid receptor ligands. Bioorg Med Chem Lett 2010;20:503-7
  • Ananthan S. Opioid ligands with mixed μ/delta opioid receptor interactions: an emerging approach to novel analgesics. AAPS J 2006;8:E118-25
  • Otieno MA, Bavuso N, Milano J, et al. Mechanistic investigation of N,N-diethyl-4-(phenyl-piperidin-4-ylidenemethyl)-benzamide–induced insulin depletion in the rat and RINm5F cells. Toxicol Sci 2008;105:221-9
  • Codd EE, Baker J, Brandt MR, et al. Diabetogenic effect of a series of tricyclic delta opioid agonists structurally related to cyproheptadine. Toxicol Sci 2010;117:504
  • Hintze KL, Aboul-enein HY, Fischer LJ. Isomeric specificity of diphenylmethylpiperidine in the production of rat pancreatic islet cell toxicity. Toxicology 1977;7:133-40
  • Daniels DJ, Portoghese PS. Delta-selective ligands related to naltorindole. In: Chang KJ, Porreca F, Woods JH, editors. The Delta Receptor. Marcel Decker; New York: 2004. p. 139-58
  • Nagase H, Osa Y, Nemoto T, et al. Design and synthesis of novel delta opioid receptor agonists and their pharmacologies. Bioorg Med Chem Lett 2009;19:2792-5
  • Nagase H, Nemoto T, Matsubara A, et al. Design and synthesis of KNT-127, a delta-opioid receptor agonist effective by systemic administration. Bioorg Med Chem Lett 2010;20:6302-5
  • Waldhoer M, Fong J, Jones RM, et al. A heterodimer-selective agonist shows in vivo relevance of G protein-coupled receptor dimers. Proc Natl Acad Sci USA 2005;102:9050-5
  • Ananthan S, Saini SK, Dersch CM, et al. 14-Alkoxy- and 14-acyloxypyridomorphinans: μ agonist/delta antagonist opioid analgesics with diminished tolerance and dependence side effects. J Med Chem 2012;55:8350-63
  • Zhang Q, Keenan SM, Peng Y, et al. Discovery of novel triazole-based opioid receptor antagonists. J Med Chem 2006;49:4044-7
  • Peng Y, Zhang Q, Arora S, et al. Novel delta opioid receptor agonists exhibit differential stimulation of signaling pathways. Bioorg Med Chem 2009;17:6442-50
  • Breslin HJ, Cai C, Miskowski TA, et al. Identification of potent phenyl imidazoles as opioid receptor agonists. Bioorg Med Chem Lett 2006;6:2505-8
  • Breslin HJ, Diamond CJ, Kavash RW, et al. Identification of a dual delta OR antagonist/mu OR agonist as a potential therapeutic for diarrhea-predominant irritable bowel syndrome (IBS-d). Bioorg Med Chem Lett 2012;22:4869-72
  • Carroll FI, Zhang L, Mascarella SW, et al. Discovery of the FIRST N-substituted 4beta-methyl-5-(3-hydroxyphenyl)morphan to possess highly potent and selective opioid delta receptor antagonist activity. J Med Chem 2004;47:281-4
  • Lovell KM, Prevatt-Smith KM, Lozama A, Prisinzano TE. Synthesis of neoclerodane diterpenes and their pharmacological effects. Curr Top Chem 2011;299:141-85
  • Coop A, Rice KC. Role of delta-opioid receptors in biological processes. Drug News Perspect 2000;13:481-7
  • Gallantine EL, Meert TF. A comparison of the antinociceptive and adverse effects of the mu-opioid agonist morphine and the delta-opioid agonist SNC80. Basic Clin Pharmacol Toxicol 2005;97:39-51
  • Pradhan AA, Befort K, Nozaki C, et al. The delta opioid receptor: an evolving target for the treatment of brain disorders. Trends Pharmacol Sci 2011;32:581-90
  • Petrillo P, Angelici O, Bingham S, et al. Evidence for a selective role of the delta-opioid agonist [8R-(4bS*,8aalpha,8abeta,12bbeta)]7,10-dimethyl-1-methoxy-11-(2-methylpropyl)oxycarbonyl 5,6,7,8,12,12b-hexahydro-(9H)-4,8-methanobenzofuro[3,2-e]pyrrolo[2,3-g]isoquinoline Hydrochloride (SB-235863) in blocking hyperalgesia associated with inflammatory and neuropathic pain responses. J Pharmacol Exp Ther 2003;307:1079-89
  • Fraser GL, Gaudreau GA, Clarke PBS, et al. Antihyperalgesic effects of delta opioid agonists in a rat model of chronic inflammation. Br J Pharmacol 2000;129:1668-72
  • Brandt MR, Furness MS, Mello NK, et al. Antinociceptive effects of delta-opioid agonists in rhesus monkeys: effects on chemically induced thermal hypersensitivity. J Pharmacol Exp Ther 2001;296:939-46
  • Holdridge SV, Cahill CM. Spinal administration of a delta opioid receptor agonist attenuates hyperalgeia and allodynia in a rat model of neuropathic pain. Eur J Pain 2007;11:685-93
  • Nichols ML, Bian D, Ossipov MH, et al. Regulation of morphine antiallodynic efficacy by cholecyctokinin in a model of neuropathic pain in rats. J Pharmacol Exp Ther 1995;275:1339-45
  • Danzebrink RM, Green SA, Gebhart GF. Spinal mu and delta, but not kappa, opioid-receptor agonists attenuate responses to noxious colorectal distension in the rat. Pain 1995;63:39-47
  • Craft RM, Henley SA, Hmseth RC, et al. Opioid antinociception in a rat model of visceral pain: systemic versus local drug administration. J Pharmacol Exp Ther 1995;275:1535-42
  • Brainin-Mattos J, Smith ND, Malkmus S, et al. Cancer-related bone pain is attenuated by a systemically available delta-opioid receptor agonist. Pain 2006;122:174-81
  • Otis V, Sarret P, Gendron L. Spinal activation of delta opioid receptors alleviates cancer-related bone pain. Neuroscience 2011;183:221-9
  • Nozaki C, Bourdonnec BL, Reiss D, et al. delta-Opioid mechanisms for ADL5747 and ADL5859 effects in mice: analgesia, locomotion, and receptor internalization. J Pharmacol Exp Ther 2012;342:799-807
  • Broom DC, Jutkiewicz EM, Rice KC, et al. Behavioral effects of delta-opioid receptor agonists: potential antidepressants? Jpn J Pharmacol 2002;90:1-6
  • Jutkiewicz EM, Woods JH. Antidepressant-like effects of delta opioid receptor agonists. In: Chang KJ, Porreca F, Woods JH, editors. The Delta Receptor. Marcel Decker; New York: 2004. p. 355-71
  • Jutkiewicz EM. The antidepressant-like effects of delta-opioid receptor agonists. Mol Interv 2006;6:162-9
  • Berrocoso E, Sánchez-Blázquez P, Garzón J, Mico JA. Opiates as antidepressants. Curr Pharm Des 2009;15:1612-22
  • Broom DC, Jutkiewicz EM, Folk JE, et al. Nonpeptidic delta-opioid receptor agonists reduce immobility in the forced swim assay in rats. Neuropsychopharmacology 2002;26:744-55
  • Saitoh A, Kimura Y, Suzuki T, et al. Potential anxiolytic and antidepressant-like activities of SNC80, a selective delta-opioid agonist, in behavioral models in Rodents. J Pharmacol Sci 2004;95:374-80
  • Saitoh A, Sugiyama A, Nemoto T, et al. The novel delta opioid receptor agonist KNT-127 produces antidepressant-like and antinociceptive effects in mice without producing convulsions. Behav Brain Res 2011;223:271-9
  • Saitoh A, Yamada M, Yamada M, et al. Antidepressant-like effects of the delta-opioid receptor agonist SNC80 ([(+)-4-[(alphaR)-alpha-[(2S,5R)-2,5-dimethyl-4-(2-propenyl)-1-piperazinyl]-(3-methoxyphenyl)methyl]-N,N-diethylbenzamide) in an olfactory bulbectomized rat model. Brain Res 2008;1208:160-9
  • Kelly JP, Wrynn AS, Leonard BE. The olfactory bulbectomized rat as a model of depression: an update. Pharmacol Ther 1997;74:299-316
  • Saitoh A, Yoshikawa Y, Onodera K, Kamei J. Role of delta-opioid receptor subtypes in anxiety-related behaviors in the elevated plus-maze in rats. Psychopharmacology (Berl) 2005;182:327-34
  • Hudzik TJ, Maciag C, Smith MA, et al. Preclinical pharmacology of AZD2327: a highly selective agonist of the delta-opioid receptor. J Pharmacol Exp Ther 2011;338:195-204
  • A Phase IIa, Multi-center, Randomized, Double-Blind, Double-Dummy, Active and Placebo Controlled, Parallel Group Study to Assess the Efficacy and Safety of AZD7268 in Patients with Major Depressive Disorder, Clinical Study Report Synopsis. 2010. Available from: http://www.astrazenecaclinicaltrials.com/_mshost800325/content/clinical-trials/resources/pdf/D1151C00005
  • Gross GJ. Role of opioids in acute and delayed preconditioning. J Mol Cell Cardiol 2003;35:709-18
  • Gross GJ, Patel HH, Fryer RM, et al. Cardioprotection and delta opioid receptors. In: Chang KJ, Porreca F, Woods JH, editors. The Delta Receptor. Marcel Decker, New York; 2004. p. 451-66
  • Schultz JEJ, Hsu AK, Nagase H, Gross GJ. TAN-67, a delta1-opioid receptor agonist, reduces infarct size via activation of Gi/o proteins and KATP channels. Am J Physiol Heart Circ Physiol 1998;274:H909-14
  • Peart JN, Patel HH, Gross GJ. delta-Opioid receptor activation mimics ischemic preconditioning in the canine heart. J Cardiovasc Pharmacol 2003;42:78-81
  • Fryer RM, Hsu AK, Eells JT, et al. Opioid-induced second window of cardioprotection potential role of mitochondrial KATP channels. Circ Res 1999;84:846-51
  • Patel HH, Hsu A, Moore J, Gross GJ. BW373U86, a delta opioid agonist, partially mediates delayed cardioprotection via a free radical mechanism that is independent of opioid receptor stimulation. J Mol Cell Cardiol 2001;33:1455-65
  • Fryer RM, Hsu AK, Nagase H, Gross GJ. Opioid-induced cardioprotection against myocardial infarction and arrhythmias: mitochondrial versus sarcolemmal ATP-sensitive potassium channels. J Pharmacol Exp Ther 2000;294:451-7
  • Bell SP, Sack MN, Patel A, et al. Delta opioid receptor stimulation mimics ischemic preconditioning in human heart muscle. J Am Coll Cardiol 2000;36:2296-302
  • Feng Y, He X, Yang Y, et al. Current research on opioid receptor function. Curr Drug Target 2012;13:230-46
  • Zhang J, Haddad GG, Xia Y. delta-, but not mu- and kappa-, opioid receptor activation protects neocortical neurons from glutamate-induced excitotoxic injury. Brain Res 2000;885:143-53
  • Zhao P, Huang Y, Zuo Z. Opioid preconditioning induces opioid receptor-dependent delayed neuroprotection against ischemia in rats. J Neurophthol Exp Neurol 2006;65:945-52
  • Horiuchi T, Kawaguchi M, Sakamoto T, et al. The effects of the delta-opioid agonist SNC80 on hind-limb motor function and neuronal injury after spinal cord ischemia in rats. Anesth Analg 2004;99:235-40
  • Wang S, Duan Y, Su D, et al. Delta opioid peptide [d-Ala2, d-Leu5] enkephalin (DADLE) triggers postconditioning against transient forebrain ischemia. Eur J Pharmacol 2011;658:140-4
  • Comer SD, Hoenicke EM, Sable AI, et al. Convulsive effects of systemic administration of the delta opioid agonist BW373U86 in mice. J Pharmacol Exp Ther 1993;267:888-95
  • Hong EJ, Rice KC, Calderon S, et al. Convulsive behavior of nonpeptidic delta-opioid ligands: comparison of SNC80 and BW373U86 in mice. Analgesia 1998;3:269-76
  • Broom DC, Jutkiewicz EM, Folk JE, et al. Convulsant activity of a non-peptidic delta-opioid receptor agonist is not required for its antidepressant-like effects in Sprague-Dawley rats. Psychopharmacology (Berl) 2002;164:42-8
  • Dykstra LA, Schoenbaum GM, Yarbrough J, et al. A novel delta opioid agonist, BW373U86, in squirrel monkeys responding under a schedule of shock titration. J Pharmacol Exp Ther 1993;267:875-82
  • Pakarinen ED, Woods JH, Moerschbaecher JM. Repeated acquisition of behavioral chains in squirrel monkeys: comparisons of a Mu, kappa and delta opioid agonist. J Pharmacol Exp Ther 1995;272:552-9
  • Negus SS, Butelman ER, Chang KJ, et al. Behavioral effects of the systemically active delta opioid agonist BW373U86 in Rhesus monkeys. J Pharmacol Exp Ther 1994;270:1025-34
  • Negus SS, Gatch MB, Mello NK, et al. Behavioral effects of the delta-selective opioid agonist SNC80 and related compounds in rhesus monkeys. J Pharmacol Exp Ther 1998;286:362-75
  • Danielsson I, Gasior M, Stevenso GW, et al. Electroencephalographic and convulsant effects of the delta opioid agonist SNC80 in rhesus monkeys. Pharmacol Biochem Behav 2006;85:428-34
  • Broom DC, Nitsche JF, Pintar JE, et al. Comparison of receptor mechanisms and efficacy requirements for delta-agonist-induced convulsive activity and antinociception in mice. J Pharmacol Exp Ther 2002;303:723-9
  • Jutkiewicz EM, Kaminsky ST, Rice KC, et al. Differential behavioral tolerance to the delta-opioid agonist SNC80 ([(+)-4-[(alphaR)-alpha-[(2S,5R)-2,5-dimethyl-4-(2-propenyl)-1-piperazinyl]-(3-methoxyphenyl)methyl]-N,N-diethylbenzamide) in Sprague-Dawley rats. J Pharmacol Exp Ther 2005;315:41-22
  • Jutkiewicz EM, Rice KC, Traynor JR, Woods JH. Separation of the convulsions and antidepressant-like effects produced by the delta-opioid agonist SNC80 in rats. Psychopharmacology (Berl) 2005;182:588-96
  • Bourdonnec BL, Windh RT, Ajello CW, et al. Potent, orally bioavailable delta opioid receptor agonists for the treatment of pain: discovery of N,N-diethyl-4-(5-hydroxyspiro-[chromene-2,4′-piperidine]-4-yl)benzamide (ADL5859). J Med Chem 2008;51:5893-6
  • Bourdonnec BL, Windh RT, Leister LK, et al. Spirocyclic delta opioid receptor agonists for the treatment of pain: discovery of N,N-diethyl-3-hydroxy-4-(spiro[chromene-2,4′-piperidine]-4-yl)benzamide (ADL5747). J Med Chem 2009;52:5685-702
  • Codd EE, Carson JR, Colburn RW, et al. JNJ-20788560 [9-(8-azabicyclo[3.2.1]oct-3-ylidene)-9hxanthene-3-carboxylic acid diethylamide], a selective delta opioid receptor agonist, is a potent and efficacious antihyperalgesic agent that does not produce respiratory depression, pharmacologic tolerance, or physical dependence. J Pharmacol Exp Ther 2009;329:241-51
  • Ardent Pharmaceuticals. Methods of treating sexual dysfunctions with delta opioid receptor agonist compounds. WO03057223; 2003
  • New York University. Therapeutic agents for the treatment of disorders causing sensation of suffocation. WO10030681; 2010
  • Wade PR, Palmer JM, McKenney S, et al. Modulation of gastrointestinal function by MuDelta, a mixed μ opioid receptor agonist/delta opioid receptor antagonist. Br J Pharmacol 2012;167:1111-25
  • Web page of Furiex Pharmaceuticals. Available from: http://www.furiex.com/pipeline/discoverydevelopment-pipeline/mu-delta/
  • Shionogi. 6,7-Unsaturated-7-carbamoyl substituted morphinan derivatives. WO06126637; 2006
  • Shionogi. 6,7-Unsaturated-7-carbamoyl substituted morphinan derivatives. WO06126529; 2006
  • Annual report 2011 of Shionogi. Available from: http://www.shionogi.co.jp/ir_en/report/index.html
  • Shionogi. Therapeutic agent for constipation. WO06064780; 2006
  • Shionogi. Therapeutic agent for nausea and/or vomiting. WO07043518; 2007
  • Gavériaux-Ruff C, Filliol D, Simonin F, et al. Immunosuppression by delta-opioid antagonist naltrindole: delta- and triple μ/delta/kappa-opioid receptor knockout mice reveal a nonopioid activity. J Pharmacol Exp Ther 2001;298:1193-8
  • Miyata Y, Fujii H, Osa Y, et al. Opioid delta1 receptor antagonist 7-benzylidenenaltrexone as an effective resistance reverser for chloroquine-resistant Plasmodium chabaudi. Bioorg Med Chem Lett 2011;21:4710-12
  • Granier S, Manglik A, Kruse AC, et al. Structure of the delta-opioid receptor bound to naltrindole. Nature 2012;485:400-4
  • Manglik A, Kruse AC, Kobilka TS, et al. Crystal structure of the μ-opioid receptor bound to a morphinan antagonist. Nature 2012;485:321-6
  • Wu H, Wacker D, Mileni M, et al. Structure of the human kappa-opioid receptor in complex with JDTic. Nature 2012;485:327-32
  • Thompson AA, Liu W, Chun E, et al. Structure of the nociceptin/orphanin FQ receptor in complex with a peptide mimetic. Nature 2012;485:395-9
  • Holt JDS, Watson MJ, Chang JP, et al. DPI-221 [4-((alpha-S)-alpha-((2S,5R)-2,5-dimethyl-4-(3-fluorobenzyl)-1-piperazinyl)benzyl)-N,N-diethylbenzamide]: a novel nonpeptide delta receptor agonist producing increased micturition interval in normal rats. J Pharmacol Exp Ther 2005;315:601-8
  • McCauley Jr JP, Dantzman CL, King MM, et al. Multiparameter exploration of piperazine derivatives as delta-opioid receptor agonists for CNS indications. Bioorg Med Chem Lett 2012;22:1169-73
  • AstraZeneca. 4-(Phenyl-piperaziniyl-methyl)benzamide derivatives and their use for the treatment of pain or gastrointestinal disorders. WO04041800; 2004
  • Kim IJ, Ullrich T, Janetka JW, et al. Diaryldimethylpiperazine ligands with mu- and delta-opioid receptor affinity: synthesis of (+)-4-[(alphaR)-alpha-(4-allyl-(2S,5S)-dimethylpiperazin-1-yl)-(3-hydroxyphenyl)methyl]-N-ethyl-nphenylbenzamide and (–)-4-[(alphaR)-alpha-alpha-2S,5S)-dimethylpiperazin-1-yl)-(3-hydroxyphenyl)methyl]-N-ethyl-N-phenylbenzamide. Bioorg Med Chem 2003;11:4761-8
  • Bishop MJ, Garrido DM, Boswell GE, et al. 3-(alphaR)-alpha-((2S,5R)-4-Allyl-2,5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)-N-alkyl-N-arylbenzamides: potent, non-peptidic agonists of both the μ and delta opioid receptors. J Med Chem 2003;46:623-33
  • Gengo PJ, Pettit HO, O'Neill SJ, et al. DPI-3290 [(+)-3-((alpha-R)-alpha-((2S,5R)-4-Allyl-2,5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)-N-(3-fluorophenyl)-N-methylbenzamide]. I. A mixed opioid agonist with potent antinociceptive activity. J Pharmacol Exp Ther 2003;307:1221-6
  • Ardent Pharmaceuticals. An enantiomerically pure diarylmethylpiperazine and methods of using same. WO03026660; 2003
  • AstraZeneca. Diarylmethyl piperazine derivatives, preparations thereof and uses thereof. WO06091160; 2006
  • AstraZeneca. Novel compounds. WO01045637; 2001
  • AstraZeneca. Novel compounds. WO01046174; 2001
  • Holl R, Jung B, Schepmann D, et al. Synthesis and pharmacological evaluation of SNC80 analogues with a bridged piperazine ring. ChemMedChem 2009;4:2111-22
  • Neuroscienze PharmaNess. Diazacyclic compounds having affinity for opioid receptors. EP2338889; 2011
  • Ardent Pharmaceuticals. Compounds of novel opioid compounds and methods of use thereof. WO06113468; 2006
  • Pfizer. Compounds as delta opioid agonists. US6200978; 2001
  • Middleton DS, Maw GN, Challenger C, et al. Highly potent and selective zwitterionic agonists of the delta-opioid receptor. Part 1. Bioorg Med Chem Lett 2006;16:905-10
  • Wei ZY, Brown W, Takasaki B, et al. N,N-Diethyl-4-(phenylpiperidin-4-ylidenemethyl)benzamide: a novel, ExceptioNALLY SELECTIVE, potent delta opioid receptor agonist with oral bioavailability and its analogue. J Med Chem 2000;43:3895-905
  • AstraZeneca. 4[Piperidin-4-yliden-(3-carbamoylphenyl)methyl]benzamide derivatives and their use for the treatment of pain, spinal injuries or gastrointestinal disorders. WO03029215l; 2003
  • AstraZeneca. Diarylmethylidene piperidine derivatives, preparations thereof and uses thereof. WO04063157; 2004
  • AstraZeneca. 4-{‘3-(Sulfonylamino)phenyl!' 1-(cyanomethyl)piperidin-4-ylidene! Methyl}benzamide derivatives as delta opioid receptor ligands for the treatment of pain, anxiety and functional gastrointestinal disorder. WO04063193; 2004
  • Astra Pharma. Novel compounds with analgesic effect. US01021715; 2001
  • AstraZeneca. Diarylmethylidene piperidine derivatives and their use as delta opioid receptor agonists. WO04101520; 2004
  • AstraZeneca. Diarylmethylidene piperidine derivatives, preparations thereof and uses thereof. WO04101522; 2004
  • Dantzman CL, King MM, Ernst GE, et al. 4-Piperidin-4-ylidenemethyl-benzamides as delta-opioid receptor agonists for CNS indications: identifying clinical candidates. Bioorg Med Chem Lett 2012;22:1174-8
  • Carson JR, Coats SJ, Codd EE, et al. N,N-Dialkyl-4-[(8-azabicyclo[3.2.1]-oct-3-ylidene)phenylmethyl]-benzamides, potent, selective delta opioid agonists. Bioorg Med Chem Lett 2004;14:2109-12
  • Johnson & Johnson. 3-(Diarylmethylene)-8-azabicyclo[3.2.1]octane derivatives. US050004163; 2005
  • Johnson & Johnson. 3-(Diheteroarylmethylene)-8-azabicyclo[3.2.1]octane and 3-((aryl)(heteroaryl)methylene)-8-azabicyclo[3.2.1]octane derivatives. US050171099; 2005
  • Coats SJ, Schulz MJ, Carson JR, et al. Parallel methods for the preparation and SAR exploration of N-ethyl-4-[(8-alkyl-8-aza-bicyclo[3.2.1]-oct-3-ylidene)-aryl-methyl]-benzamides, powerful mu and delta opioid agonists. Bioorg Med Chem Lett 2004;14:5493-8
  • Janssen Pharmaceutica. Tricyclic opioid modulators. WO06138528; 2006
  • Janssen Pharmaceutica. Tricyclic delta-opioid modulators. WO07030089; 2007
  • Codd EE, Ma J, Zhang SP, et al. Ex vivo delta opioid receptor autoradiography: CNS receptor occupancy of two novel compounds over their antihyperalgesic dose range. Pharmacol Biochem Behav 2010;96:130-5
  • Ortho-McNeil Pharmaceutical. 4-[Aryl(piperidin-4-yl)] aminobenzamides which bind to the delta-opioid receptor. AU03220725; 2003
  • Thomas JB, Herault XM, Rothman RB, et al. Factors influencing agonist potency and selectivity for the opioid delta receptor are revealed in structure-activity relationship studies of the 4-[(N-substituted-4-piperidinyl)arylamino]-N,N-diethylbenzamides. J Med Chem 2001;44:972-87
  • AstraZeneca. Novel compounds. WO01046263; 2001
  • Jones P, Griffin AM, Gawell L, et al. N,N-Diethyl-4-[(3-hydroxyphenyl)(piperidin-4-yl)amino] benzamide derivatives: The development of diaryl amino piperidines as potent delta opioid receptor agonists with in vivo anti-nociceptive activity in rodent models. Bioorg Med Chem Lett 2009;19:5994-8
  • Janssen Pharmaceutica. Tricyclic delta-opioid modulators. WO06074388; 2006
  • Janssen Pharmaceutica. Tricyclic delta-opioid modulators. WO06069276; 2006
  • Janssen Pharmaceutica. Tricyclic delta-opioid modulators. WO06069277; 2006
  • Janssen Pharmaceutica. Tricyclic delta-opioid modulators. WO06069275; 2006
  • Pfizer. 4-Phenyl-4-heteroarylpiperidine derivatives as opioid receptor ligands. EP1038872; 2000
  • Trabanco AA, Pullan S, Alonso JM, et al. 4-Phenyl-4-[1H-imidazol-2-yl]-piperidine derivatives, a novel class of selective delta-opioid agonists. Bioorg Med Chem Lett 2006;16:146-9
  • Trabanco AA, Aerts N, Alvarez RM, et al. 4-Phenyl-4-[1H-imidazol-2-yl]-piperidine derivatives as non-peptidic selective delta-opioid agonists with potential anxiolytic/antidepressant properties. Part 2. Bioorg Med Chem Lett 2007;17:3860-3
  • Pfizer. 1-Diphenylmethylpyrazole derivatives as opioid receptor ligands. US0369241; 2003
  • Nortey SO, Baxter EW, Codd EE, et al. Piperazinyl benzamidines: synthesis and affinity for the delta opioid receptor. Bioorg Med Chem Lett 2001;11:1741-3
  • Janssen Pharmaceutica. Benzyl substituted (piperidin-4-yl)aminobenzamido derivatives as delta-opioid receptor modulators. WO04035541; 2004
  • Janssen Pharmaceutica. Substituted aminoquinuclidine compounds. WO04035574; 2004
  • Zhang A, Li F, Ding C, et al. Synthesis and pharmacological evaluation of 6,7-indolo/thiazolo-morphinans–further SAR of levorphanol. J Med Chem 2007;50:2747-51
  • Smith TA, Thatcher LN, Coop A. 3-Hydroxy-4-methoxyindolomorphinans as delta opioid selective ligands. Bioorg Med Chem Lett 2007;17:5175-6
  • Sharma SK, Jones RM, Metzger TG, et al. Transformation of a kappa-opioid receptor antagonist to a kappa-agonist by transfer of a guanidinium group from the 5′- to 6′-position of naltrindole. J Med Chem 2001;44:2073-9
  • Sakami S, Maeda M, Kawai K, et al. Structure-antitussive activity relationships of naltrindole derivatives. Identification of novel and potent antitussive agents. J Med Chem 2008;51:4404-11
  • Sakami S, Kawai K, Maeda M, et al. Design and synthesis of a metabolically stable and potent antitussive agent, a novel delta opioid receptor antagonist, TRK-851. Bioorg Med Chem 2008;16:956-67
  • Grundt P, Jales AR, Traynor JR, et al. 14-Amino, 14-alkylamino, and 14-acylamino analogs of oxymorphindole. Differential effects on opioid receptor binding and functional profiles. J Med Chem 2003;46:1563-6
  • Schütz J, Dersch CM, Horel R, et al. Synthesis and biological evaluation of 14-alkoxymorphinans. 17. Highly delta opioid receptor selective 14-alkoxy-substituted indolo- and benzofuromorphinans. J Med Chem 2002;45:5378-83
  • Biyashev D, Monory K, Benyhe S, et al. Novel delta-opioid-receptor-selective ligands in the 14-alkoxy-substituted indolo- and benzofuromorphinan series. Helv Chim Acta 2001;84:2015-21
  • Grundt P, Martinez-Bermejo F, Lewis JW, Husbands SM. The 14-alkyl- and 14-Alkenyl-5beta-methylindolomorphinan series provide delta-selective partial opioid agonists. Helv Chim Acta 2003;86:793-8
  • Yu H, Prisinzano T, Dersch CM, et al. Synthesis and biological activity of 8beta-substituted hydrocodone indole and hydromorphone indole derivatives. Bioorg Med Chem Lett 2002;12:165-8
  • Srivastava SK, Shefali S, Miller CN, et al. Effects of substitution on the pyrrole N atom in derivatives of tetrahydronaltrindole, tetrahydrooxymorphindole, and a related 4,5-epoxyphenylpyrrolomorphinan. J Med Chem 2004;47:6645-8
  • Dondio G, Ronzoni S, Farina C, et al. Selective delta opioid receptor agonists for inflammatory and neuropathic pain. Il Farmaco 2001;56:117-19
  • GlaxoSmithKline. Pyrrole-condensed morphinoid derivatives. WO02030936; 2002
  • GlaxoSmithKline. Morphinoid derivatives as delta-opioid agonists and antagonists. WO02030935; 2002
  • Srivastava SK, Husbands SM, Aceto MD, et al. 4′-Arylpyrrolomorphinans: effect of a pyrrolo-N-benzyl substituent in enhancing delta-opioid antagonist activity. J Med Chem 2002;45:537-40
  • Southern Research. Pyridomorphinans, thienomorphinans and use thereof. WO01012197; 2001
  • Ananthan S, Khare NK, Saini SK, et al. Novel ligands for the opioid receptors: synthesis and structure–activity relationships among 5′-Aryl and 5′-heteroaryl 17-cyclopropylmethyl-4,5alpha-epoxypyrido[2′,3′:6,7]morphinans. Bioorg Med Chem 2003;11:4143-54
  • Ananthan S, Khare NK, Saini SK, et al. Identification of opioid ligands possessing mixed μ agonist/delta antagonist activity among pyridomorphinans derived from naloxone, oxymorphone, and hydromorphone. J Med Chem 2004;47:1400-12
  • Ananthan S, Kezar HS III, Saini SK, et al. Synthesis, opioid receptor binding, and functional activity of 5′-substituted 17-cyclopropylmethylpyrido[2′,3′:6,7]morphinans. Bioorg Med Chem Lett 2003;13:529-32
  • Kitasato University and Nippon Chemiphar. Morphinan derivative. WO12102360; 2012
  • Pfizer. Spiropiperidine derivatives. WO07057775; 2007
  • Adolor. Spirocyclic heterocyclic derivatives and methods of their use. WO07118151; 2007
  • Janssen Pharmaceutica. Phenoxy-substituted pyrimidines as opioid receptor modulators. WO11053701; 2011
  • Janssen Pharmaceutica. Pyrazines as delta opioid receptor modulators. WO11053696; 2011
  • Breslin HJ, Miskowski TA, Rafferty BM, et al. Rationale, design, and synthesis of novel phenyl imidazoles as opioid receptor agonists for gastrointestinal disorders. J Med Chem 2004;47:5009-20
  • Meiji Seika Kaisha. Phenoxyalkylamine derivatives useful as opioid delta receptor agonists. WO0160796; 2001
  • Meiji Seika Kaisha. Spiro compounds useful as opioid delta receptor agonist. WO0146192; 2001
  • Meiji Seika Kaisha. Diphenylalkylamine derivatives useful as opioid delta receptor agonists. WO0170689; 2001
  • Grünenthal. Die folgenden angaben sind den vom anmelder eingereichten unterlagen entnommen. DE19857475; 2000
  • Grünenthal. Acridinderivate. EP0970949; 2000
  • AstraZeneca. 1,2,3,4-Tetrahydroisoquinoline derivatives, preparations thereof and uses thereof. WO05061484; 2005
  • Barn DR, Caulfield WL, Cottney J, et al. Parallel synthesis and biological activity of a new class of high affinity and selective delta-opioid ligand. Bioorg Med Chem 2001;9:2609-24
  • Jung B, Englberger W, FrÓ§hlich R, et al. Synthesis and pharmacological evaluation of bicyclic SNC80 analogues with separated benzhydryl moiety. Bioorg Med Chem 2008;16:2870-85
  • Harding WW, Schmidt M, Tidgewell K, et al. Synthetic studies of neoclerodane diterpenes from Salvia divinorum: semisynthesis of salvinicins A and B and other chemical transformations of salvinorin A. J Nat Prod 2006;69:107-12
  • Carroll AR, Kaiser SM, Davis RA, et al. A bastadin with potent and selective delta-opioid receptor binding affinity from the Australian sponge Ianthella flabelliformis. J Nat Prod 2010;73:1173-6
  • Carroll AR, Arumugan T, Redburn J, et al. Hasubanan alkaloids with delta-opioid binding affinity from the aerial parts of Stephania japonica. J Nat Prod 2010;73:988-91

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