Diaryldiamines with dual inhibition of the histamine H3 receptor and the norepinephrine transporter and the efficacy of 4-(3-(methylamino)-1- phenylpropyl)-6-(2-(pyrrolidin-1-yl)ethoxy)naphthalen-1-ol in pain

Journal of Medicinal Chemistry

Volumn 53, Issue 21, 2010, Pages 7869-7873

  Altenbach, Robert J ^a   Black, Lawrence A ^a   Strakhova, Marina I ^a   Manelli, Arlene M ^a   Carr, Tracy L ^a   Marsh, Kennan C ^a   Wetter, Jill M ^a   Wensink, Erica J ^a   Hsieh, Gin C ^a   Honore, Prisca ^a   Garrison, Tiffany Runyan ^a   Brioni, Jorge D ^a   Cowart, Marlon D ^a  

^a ABBOTT LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 [3 (METHYLAMINO) 1 PHENYLPROPYL] 6 [2 (PYRROLIDIN 1 YL)ETHOXY]NAPHTHALEN 1 OL; ANALGESIC AGENT; DICLOFENAC; HISTAMINE H3 RECEPTOR ANTAGONIST; N 1 METHYL N 2 PHENYL N 2 [4 [2 (PYRROLIDIN 1 YL)ETHOXY]PHENYL]ETHANE 1,2 DIAMINE; N 1 METHYL N 3 PHENYL N 3 [4 [2 (PYRROLIDIN 1 YL)ETHOXY]PHENYL]PROPANE 1,3 DIAMINE; N METHYL 3 PHENYL 3 [4 [2 (PYRROLIDIN 1 YL)ETHOXY]PHENYL]PROPAN 1 AMINE; N METHYL 3 PHENYL 3 [6 [2 (PYRROLIDIN 1 YL)ETHOXY]NAPHTHALEN 1 YLOXY]PROPAN 1 AMINE; N METHYL 4 PHENYL 4 [4 [2 (PYRROLIDIN 1 YL)ETHOXY]PHENYL]BUTAN 1 AMINE; NAPHTHALENE DERIVATIVE; NORADRENALIN TRANSPORTER ANTAGONIST; PROTEIN INHIBITOR; UNCLASSIFIED DRUG;

ANALGESIA; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BINDING AFFINITY; CONTROLLED STUDY; DOSE RESPONSE; DRUG BIOAVAILABILITY; DRUG EFFICACY; DRUG HALF LIFE; DRUG PENETRATION; DRUG POTENCY; DRUG RECEPTOR BINDING; MAXIMUM PLASMA CONCENTRATION; NONHUMAN; OSTEOARTHRITIS; PLASMA PROTEIN BINDING; RAT; RECEPTOR OCCUPANCY; STRUCTURE ACTIVITY RELATION; TIME TO MAXIMUM PLASMA CONCENTRATION;

ANIMALS; HISTAMINE H3 ANTAGONISTS; NAPHTHOLS; NOREPINEPHRINE PLASMA MEMBRANE TRANSPORT PROTEINS; OSTEOARTHRITIS; PAIN; PYRROLIDINES; RATS; RATS, SPRAGUE-DAWLEY; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 78149261499     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm100666w     Document Type: Article

References (40)

1. Parsons, M. E.; Ganellin, C. R. Histamine and its receptors Br. J. Pharmacol. 2006, 147 (S1) S127-S135
2. Leurs, R.; Bakker, R. A.; Timmerman, H.; de Esch, I. J. P. The histamine H3 receptor: from gene cloning to H3 receptor drugs Nat. Rev. Drug Discovery 2005, 4, 107-120
3. Arrang, J. M.; Garbarg, M.; Schwartz, J. C. Auto-inhibition of brain histamine release mediated by a novel class (H3) of histamine receptor Nature 1983, 302, 832-837
4. Barbier, A. J.; Bradbury, M. J. Histaminergic control of sleep-wake cycles: recent therapeutic advances for sleep and wake disorders CNS Neurol. Disord.: Drug Targets 2007, 6, 31-43
5. Gemkow, M. J.; Davenport, A. J.; Harich, S.; Ellenbroek, B. A.; Cesura, A.; Hallett, D. The histamine H3 receptor as a therapeutic drug target for CNS disorders Drug Discovery Today 2009, 14, 509-515
6. Schlicker, E.; Malinowska, B.; Kathmann, M.; Gothert, M. Modulation of neurotransmitter release via histamine H3 heteroreceptors Fundam. Clin. Pharmacol. 1994, 8, 128-137
7. Sander, K.; Kottke, T.; Stark, H. Histamine H3 receptor antagonists go to clinics Biol. Pharm. Bull. 2008, 31, 2163-2181
8. Farzin, D.; Asghari, L.; Nowrouzi, M. Rodent antinociception following acute treatment with different histamine receptor agonists and antagonists Pharmacol., Biochem. Behav. 2002, 72, 751-760
9. Malmberg-Aiello, P.; Lamberti, C.; Ghelardini, C.; Giotti, A.; Bartolini, A. Role of histamine in rodent antinociception Br. J. Pharmacol. 1994, 111, 1269-1279
10. Medhurst, S. J.; Collins, S. D.; Billinton, A.; Bingham, S.; Dalziel, R. G.; Brass, A.; Roberts, J. C.; Medhurst, A. D.; Chessell, I. P. Novel histamine H3 receptor antagonists GSK189254 and GSK334429 are efficacious in surgically-induced and virally-induced rat models of neuropathic pain Pain 2008, 138, 61-69
11. http://www.clinicaltrials.gov.
12. Benarroch, E. E. Descending monoaminergic pain modulation: bidirectional control and clinical relevance Neurology 2008, 71, 217-221
13. Giovannoni, M. P.; Ghelardini, C.; Vergelli, C.; Dal Piaz, V. α2-Agonists as analgesic agents Med. Res. Rev. 2009, 29, 339-368
14. Zhou, Jia. Norepinephrine transporter inhibitors and their therapeutic potential Drugs Future 2004, 29, 1235-1244
15. Koch, S.; Hemrick-Luecke, S. K.; Thompson, L. K.; Evans, D. C.; Threlkeld, P. G.; Nelson, D. L.; Perry, K. W.; Bymaster, F. P. Comparison of effects of dual transporter inhibitors on monoamine transporters and extracellular levels in rats Neuropharmacology 2003, 45, 935-944
16. Fishbain, D.; Berman, K.; Kajdasz, D. K. Duloxetine for neuropathic pain based on recent clinical trials Curr. Pain Headache Rep. 2006, 10, 199-204
17. Leventhal, L.; Smith, V; Hornby, G.; Andree, T. H.; Brandt, M. R.; Rogers, K. E. Differential and synergistic effects of selective norepinephrine and serotonin reuptake inhibitors in rodent models of pain J. Pharmacol. Exp. Ther. 2007, 320, 1178-1185
18. Krell, H. V.; Leuchter, A. F.; Cook, I. A.; Abrams, M. Evaluation of reboxetine, a noradrenergic antidepressant, for the treatment of fibromyalgia and chronic low back pain Psychosomatics 2005, 46, 379-384
19. McCleane, G. Antidepressants as analgesics CNS Drugs 2008, 22, 139-156
20. Keith, J. M.; Gomez, L. A.; Letavic, M. A.; Ly, K. S.; Jablonowski, J. A.; Seierstad, M.; Barbier, A. J.; Wilson, S. J.; Boggs, J. D.; Fraser, I. C.; Mazur, C.; Lovenberg, T. W.; Carruthers, N. I. Dual serotonin transporter/histamine H3 ligands: optimization of the H3 pharmacophore Bioorg. Med. Chem. Lett. 2007, 17, 702-706
21. Apelt, J.; Ligneau, X.; Pertz, H. H.; Arrang, J.-M.; Ganellin, C. R.; Schwartz, J.-C.; Schunack, W.; Stark, H. Development of a new class of nonimidazole histamine H3 receptor ligands with combined inhibitory histamine N -methyltransferase activity J. Med. Chem. 2002, 45, 1128-1141
22. Bymaster, F. P.; Beedle, E. E.; Findlay, J.; Gallagher, P. T.; Krushinski, J. H.; Mitchell, S.; Robertson, D. W.; Thompson, D. C.; Wallace, L.; Wong, D. T. Duloxetine (Cymbalta), a dual inhibitor of serotonin and norepinephrine reuptake Bioorg. Med. Chem. Lett. 2003, 13, 4477-4480
23. Asakawa, M.; Ashton, P. R.; Boyd, S. E.; Brown, C. L.; Gillard, R. E.; Kocian, O.; Raymo, F. M.; Stoddart, J. F.; Tolley, M. S.; White, A. J. P.; Williams, D. J. Recognition of bipyridinium-based derivatives by hydroquinone- and/or dioxynaphthalene-based macrocyclic polyethers: from inclusion complexes to the self-assembly of [2]catenanes J. Org. Chem. 1997, 62, 26-37
24. Miyata, S.; Kumamoto, T.; Ishikawa, T. Practical enzymatic desymmetrization of 2-(ethoxycarbonyl)propane-1,3-diyl dihexanoate and model cyclization for the A-D ring system of lysergic acid Helv. Chim. Acta 2007, 90, 1420-1438
25. Le Bihan, G.; Rondu, F.; Pele-Tounian, A.; Wang, X.; Lidy, S.; Touboul, E.; Lamouri, A.; Dive, G.; Huet, J.; Pfeiffer, B.; Renard, P.; Guardiola-Lemaitre, B.; Manechez, D.; Penicaud, L.; Ktorza, A.; Godfroid, J.-J. Design and Synthesis of imidazoline derivatives active on glucose homeostasis in a rat model of type II diabetes. 2. Syntheses and biological activities of 1,4-dialkyl-, 1,4-dibenzyl, and 1-benzyl-4-alkyl-2-(4',5'-dihydro-1' H -imidazol-2'-yl)piperazines and isosteric analogs of imidazoline J. Med. Chem. 1999, 42, 1587-1603
26. Bergel, F.; Haworth, J. W.; Morrison, A. L.; Rinderknecht, H. Synthetic analgesics. I. Synthesis of basic benzofuran derivatives and certain 4-phenylpiperidine compounds J. Chem. Soc. 1944, 261-265
27. See Supporting Information for GTPγS data on 4 - 7 and 9.
28. See Supporting Information for analogues of 4, 5, and 8.
29. Esbenshade, T. A.; Krueger, K. M.; Miller, T. R.; Kang, C. H.; Denny, L. I.; Witte, D. G.; Yao, B. B.; Fox, G. B.; Faghih, R.; Bennani, Y. L.; Williams, M.; Hancock, A. A. Two novel and selective nonimidazole histamine H3 receptor antagonists A-304121 and A-317920: I. In vitro pharmacological effects J. Pharmacol. Exp. Ther. 2003, 305, 887-896 (Pubitemid 36617965)
30. Diarylmethane compounds had been previously known as monoamine inhibitors: Manning, J. R.; Sexton, T.; Childers, S. R.; Davies, H. M. L. 1-Naphthyl and 4-indolyl arylalkylamines as selective monoamine reuptake inhibitors Bioorg. Med. Chem. Lett. 2009, 19, 58-61
31. Lucas, M. C.; Carter, D. S.; Cai, H.-Y.; Lee, E. K.; Schoenfeld, R. C.; Steiner, S.; Villa, M.; Weikert, R. J.; Iyer, P. S. Novel, achiral aminoheterocycles as selective monoamine reuptake inhibitors Bioorg. Med. Chem. Lett. 2009, 19, 4630-4633
32. Hsieh, G. C.; Honore, P.; Pai, M.; Wensink, E. J.; Chandran, P.; Salyers, A. K.; Wetter, J. M.; Zhao, C.; Liu, H.; Decker, M. W.; Esbenshade, T. A.; Cowart, M. D.; Brioni, J. D. Antinociceptive effects of histamine H3 receptor antagonist in the preclinical models of pain in rats and the involvement of central noradrenergic systems Brain Res. 2010, 1354, 74-84
33. Chandran, P.; Pai, M.; Blomme, E. A.; Hsieh, G. C.; Decker, M. W.; Honore, P. Pharmacological modulation of movement-evoked pain in a rat model of osteoarthritis Eur. J. Pharmacol. 2009, 613, 39-45
34. Wensink, E. J.; Salyers, A. K.; Pai, M.; Lewis, L.; Decker, M. W.; Jacobson, P. B.; Hsieh, G. C.; Brioni, J. D. Duloxetine Relieves Osteoarthritic Pain in a Preclinical Rat Model. Presented at Neuroscience 2009, Chicago, IL, Oct 17-21, 2009; BB11 268.5.
35. Chappell, A. S.; Ossanna, M. J.; Liu-Seifert, H.; Iyengar, S.; Skljarevski, V.; Li, L. C.; Bennett, R. M.; Collins, H. Duloxetine, a centrally acting analgesic, in the treatment of patients with osteoarthritis knee pain: a 13-week, randomized, placebo-controlled trial Pain 2009, 146, 253-260
36. Trainor, G. L. The importance of plasma protein binding in drug discovery Expert Opin. Drug Discovery 2007, 2, 51-64
37. See Supporting Information for estimation of receptor occupancy of 5.
38. Augustine, R. L.; Pinto, F. G. Ring-opening reactions of 2-benzoylcyclopropane isocyanate J. Org. Chem. 1975, 40, 115-117
39. Method for NET binding can be found in the Supporting Information.
40. See Supporting Information section for alternate synthesis and salt formation of compounds 8 and 9.