The bivalent ligand approach leads to highly potent and selective acylguanidine-type histamine H 2 receptor agonists

Journal of Medicinal Chemistry

Volumn 55, Issue 3, 2012, Pages 1147-1160

  Birnkammer, Tobias ^a   Spickenreither, Anja ^a   Brunskole, Irena ^a   Lopuch, Miroslaw ^a   Kagermeier, Nicole ^a   Bernhardt, Günther ^a   Dove, Stefan ^a   Seifert, Roland ^b   Elz, Sigurd ^a   Buschauer, Armin ^a  

^a UNIVERSITY OF REGENSBURG   (Germany)

^b HANNOVER MEDICAL SCHOOL   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

DIMER; GUANIDINE DERIVATIVE; GUANOSINE TRIPHOSPHATASE; HISTAMINE H1 RECEPTOR; HISTAMINE H2 RECEPTOR AGONIST; HISTAMINE H3 RECEPTOR; HISTAMINE H4 RECEPTOR; IMIDAZOLE DERIVATIVE; LIGAND; TERT BUTYL 5 [3 (2 TERT BUTOXYCARBONYLGUANIDINO)PROPYL] 4 METHYLTHIAZOL 2 YLCARBAMATE; UNCLASSIFIED DRUG;

ARTICLE; BINDING ASSAY; BINDING COMPETITION; BINDING SITE; CARBON NUCLEAR MAGNETIC RESONANCE; CHEMICAL INTERACTION; CONTROLLED STUDY; CRYSTAL STRUCTURE; DRUG POTENCY; DRUG SYNTHESIS; ENZYME ACTIVE SITE; ENZYME ACTIVITY; HEART RIGHT ATRIUM; NONHUMAN; PHARMACOPHORE; PROTON NUCLEAR MAGNETIC RESONANCE; REVERSED PHASE HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; STRUCTURE ACTIVITY RELATION; THIN LAYER CHROMATOGRAPHY;

ANIMALS; CELL MEMBRANE; GTP-BINDING PROTEIN ALPHA SUBUNITS, GS; GUANIDINES; GUINEA PIGS; HEART; HISTAMINE AGONISTS; HUMANS; LIGANDS; MUTATION; PROMOTER REGIONS, GENETIC; PROTEIN MULTIMERIZATION; RECEPTORS, HISTAMINE H2; RECOMBINANT FUSION PROTEINS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84856837790     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm201128q     Document Type: Article

References (76)

1. 2-receptors Nature 1972, 236, 385-390
2. Hill, S. J.; Ganellin, C. R.; Timmerman, H.; Schwartz, J. C.; Shankley, N. P.; Young, J. M.; Schunack, W.; Levi, R.; Haas, H. L. International Union of Pharmacology. XIII. Classification of histamine receptors Pharmacol. Rev. 1997, 49, 253-278 (Pubitemid 27414915)
3. 2-receptor agonist. Part 2. Structure-activity considerations Inflammation Res. 1977, 7, 39-43 (Pubitemid 8070778)
4. Durant, G. J.; Ganellin, C. R.; Hills, D. W.; Miles, P. D.; Parsons, M. E.; Pepper, E. S.; White, G. R. The histamine H2 receptor agonist impromidine: synthesis and structure-activity considerations J. Med. Chem. 1985, 28, 1414-1422 (Pubitemid 16229727)
5. Buschauer, A. Synthesis and in vitro pharmacology of arpromidine and related phenyl(pyridylalkyl)guanidines, a potential new class of positive inotropic drugs J. Med. Chem. 1989, 32, 1963-1970 (Pubitemid 19204387)
6. 2 agonistic activity of arpromidine analogues: replacement of the pheniramine-like moiety by non-heterocyclic groups Eur. J. Med. Chem. 1992, 27, 321-330
7. 4 receptor agonist J. Pharmacol. Exp. Ther. 2005, 314, 1310-1321 (Pubitemid 41205997)
8. Igel, P.; Schneider, E.; Schnell, D.; Elz, S.; Seifert, R.; Buschauer, A. N(G)-acylated imidazolylpropylguanidines as potent histamine H4 receptor agonists: selectivity by variation of the N(G)-substituent J. Med. Chem. 2009, 52, 2623-2627
9. Igel, P.; Dove, S.; Buschauer, A. Histamine H4 receptor agonists Bioorg. Med. Chem. Lett. 2010, 20, 7191-7199
10. 2 receptor agonists ChemMedChem 2009, 4, 232-240
11. Ghorai, P.; Kraus, A.; Keller, M.; Gotte, C.; Igel, P.; Schneider, E.; Schnell, D.; Bernhardt, G.; Dove, S.; Zabel, M.; Elz, S.; Seifert, R.; Buschauer, A. Acylguanidines as bioisosteres of guanidines: NG-acylated imidazolylpropylguanidines, a new class of histamine H2 receptor agonists J. Med. Chem. 2008, 51, 7193-7204
12. 2-receptor agonists. Synthesis, in vitro pharmacology, and qualitative structure-activity relationships of substituted 4- and 5-(2-aminoethyl)thiazoles J. Med. Chem. 1992, 35, 3239-3246
13. Houston, C.; Wenzel-Seifert, K.; Bürckstümmer, T.; Seifert, R. The human histamine H2-receptor couples more efficiently to Sf9 insect cell Gs-proteins than to insect cell Gq-proteins: limitations of Sf9 cells for the analysis of receptor/Gq-protein coupling J. Neurochem. 2002, 80, 678-696 (Pubitemid 34809976)
14. George, S. R.; O'Dowd, B. F.; Lee, S. P. G-Protein-coupled receptor oligomerization and its potential for drug discovery Nat. Rev. Drug Discovery 2002, 1, 808-820 (Pubitemid 37361564)
15. Nikbin, N.; Edwards, C.; Reynolds, C. A. G-Protein coupled receptor dimerization Iran. J. Pharmacol. Ther. 2003, 2, 1-11
16. Terrillon, S.; Bouvier, M. Roles of G-protein-coupled receptor dimerization EMBO Rep. 2004, 5, 30-34 (Pubitemid 38228524)
17. Smith, N. J.; Milligan, G. Allostery at G protein-coupled receptor homo- and heteromers: uncharted pharmacological landscapes Pharmacol. Rev. 2010, 62, 701-725
18. McVey, M.; Ramsay, D.; Kellett, E.; Rees, S.; Wilson, S.; Pope, A. J.; Milligan, G. Monitoring receptor oligomerization using time-resolved fluorescence resonance energy transfer and bioluminescence resonance energy transfer J. Biol. Chem. 2001, 276, 14092-14099
19. Cvejic, S.; Devi, L. A. Dimerization of the delta opioid receptor: implication for a role in receptor internalization J. Biol. Chem. 1997, 272, 26959-26964 (Pubitemid 27452648)
20. Jordan, B. A.; Devi, L. A. G-Protein-coupled receptor heterodimerization modulates receptor function Nature 1999, 399, 697-700 (Pubitemid 29289066)
21. 2-adrenergic receptor dimerization in living cells using bioluminescence resonance energy transfer (BRET) Proc. Natl. Acad. Sci. U.S.A. 2000, 97, 3684-3689 (Pubitemid 30183363)
22. Grant, M.; Kumar, U. The role of G-proteins in the dimerisation of human somatostatin receptor types 2 and 5 Regul. Pept. 2010, 159, 3-8
23. Duran-Prado, M.; Malagon, M. M.; Gracia-Navarro, F.; Castano, J. P. Dimerization of G protein-coupled receptors: new avenues for somatostatin receptor signalling, control and functioning Mol. Cell. Endocrinol. 2008, 286, 63-68
24. Scarselli, M.; Novi, F.; Schallmach, E.; Lin, R.; Baragli, A.; Colzi, A.; Griffon, N.; Corsini, G. U.; Sokoloff, P.; Levenson, R.; Vogel, Z.; Maggio, R. D2/D3 dopamine receptor heterodimers exhibit unique functional properties J. Biol. Chem. 2001, 276, 30308-30314
25. Lee, S. P.; So, C. H.; Rashid, A. J.; Varghese, G.; Cheng, R.; Lanca, A. J.; O'Dowd, B. F.; George, S. R. Dopamine D1 and D2 receptor co-activation generates a novel phospholipase C-mediated calcium signal J. Biol. Chem. 2004, 279, 35671-35678 (Pubitemid 39100570)
26. Lukasiewicz, S.; Polit, A.; Kedracka-Krok, S.; Wedzony, K.; Mackowiak, M.; Dziedzicka-Wasylewska, M. Hetero-dimerization of serotonin 5-HT(2A) and dopamine D(2) receptors Biochim. Biophys. Acta 2010, 1803, 1347-1358
27. Zeng, F.; Wess, J. Molecular aspects of muscarinic receptor dimerization Neuropsychopharmacology 2000, 23, S19-S31
28. Hern, J. A.; Baig, A. H.; Mashanov, G. I.; Birdsall, B.; Corrie, J. E.; Lazareno, S.; Molloy, J. E.; Birdsall, N. J. Formation and dissociation of M1 muscarinic receptor dimers seen by total internal reflection fluorescence imaging of single molecules Proc. Natl. Acad. Sci. U.S.A. 2010, 107, 2693-2698
29. 1 receptor J. Pharmacol. Exp. Ther. 2004, 311, 131-138 (Pubitemid 39287792)
30. 4 receptors Mol. Pharmacol. 2006, 70, 604-615 (Pubitemid 44092321)
31. Carrillo, J. J.; Pediani, J.; Milligan, G. Dimers of class A G protein-coupled receptors function via agonist-mediated trans-activation of associated G proteins J. Biol. Chem. 2003, 278, 42578-42587 (Pubitemid 37310531)
32. 2 receptor signaling, desensitization, and agonist-induced internalization J. Biol. Chem. 1997, 272, 19464-19470 (Pubitemid 27337745)
33. Nguyen, T.; Shapiro, D. A.; George, S. R.; Setola, V.; Lee, D. K.; Cheng, R.; Rauser, L.; Lee, S. P.; Lynch, K. R.; Roth, B. L.; O'Dowd, B. F. Discovery of a novel member of the histamine receptor family Mol. Pharmacol. 2001, 59, 427-433 (Pubitemid 32179919)
34. 3 histamine receptor higher oligomers Inflammation Res. 2005, 54, S48-S49
35. Portoghese, P. S. From models to molecules: opioid receptor dimers, bivalent ligands, and selective opioid receptor probes J. Med. Chem. 2001, 44, 2259-2269 (Pubitemid 32867394)
36. Portoghese, P. S. Bivalent ligands and the message-address concept in the design of selective opioid receptor antagonists Trends Pharmacol. Sci. 1989, 10, 230-235 (Pubitemid 19146395)
37. Shonberg, J.; Scammells, P. J.; Capuano, B. Design strategies for bivalent ligands targeting GPCRs ChemMedChem 2011, 6, 963-974
38. Erez, M.; Takemori, A. E.; Portoghese, P. S. Narcotic antagonistic potency of bivalent ligands which contain β-naltrexamine. Evidence for simultaneous occupation of proximal recognition sites J. Med. Chem. 1982, 25, 847-849 (Pubitemid 12056967)
39. Decker, M.; Lehmann, J. Agonistic and antagonistic bivalent ligands for serotonin and dopamine receptors including their transporters Curr. Top. Med. Chem. 2007, 7, 347-353 (Pubitemid 46358647)
40. Halazy, S.; Perez, M.; Fourrier, C.; Pallard, I.; Pauwels, P. J.; Palmier, C.; John, G. W.; Valentin, J. P.; Bonnafous, R.; Martinez, J. Serotonin dimers: application of the bivalent ligand approach to the design of new potent and selective 5-HT(1B/1D) agonists J. Med. Chem. 1996, 39, 4920-4927 (Pubitemid 26422506)
41. Kühhorn, J.; Hübner, H.; Gmeiner, P. Bivalent dopamine D2 receptor ligands: synthesis and binding properties J. Med. Chem. 2011, 54, 4896-4903
42. Perez, M.; Jorand-Lebrun, C.; Pauwels, P. J.; Pallard, I.; Halazy, S. Dimers of 5HT1 ligands preferentially bind to 5HT1B/1D receptor subtypes Bioorg. Med. Chem. Lett. 1998, 8, 1407-1412 (Pubitemid 28261311)
43. Halazy, S. G-Protein coupled receptors bivalent ligands and drug design Expert Opin. Ther. Pat. 1999, 9, 431-446 (Pubitemid 29164348)
44. Kraus, A. Highly Potent, Selective Acylguanidine-Type Histamine H2 Receptor Agonists: Synthesis and Structure-Activity Relationships. Doctoral Thesis. University of Regensburg, Regensburg, Germany, 2007; http://epub.uni-regensburg.de/10699/.
45. 4R Agonists. Doctoral Thesis, University of Regensburg, Regensburg, Germany, 2008; http://epub.uni-regensburg.de/12093/.
46. sα J. Pharmacol. Exp. Ther. 2001, 299, 1013-1020 (Pubitemid 33104973)
47. Seifert, R.; Wenzel-Seifert, K.; Kobilka, B. K. GPCR-Galpha fusion proteins: molecular analysis of receptor-G-protein coupling Trends Pharmacol. Sci. 1999, 20, 383-389 (Pubitemid 29421620)
48. Schneider, E. H.; Seifert, R. Sf9 cells: a versatile model system to investigate the pharmacological properties of G protein-coupled receptors Pharmacol. Ther. 2010, 128, 387-418
49. Wenzel-Seifert, K.; Seifert, R. Molecular analysis of beta(2)-adrenoceptor coupling to G(s)-, G(i)-, and G(q)-proteins Mol. Pharmacol. 2000, 58, 954-966
50. 2-receptor with guanidine-type agonists Mol. Pharmacol. 2001, 60, 1210-1225 (Pubitemid 33144892)
51. 2 receptor determine the species selectivity of guanidine-type agonists and increase constitutive activity J. Pharmacol. Exp. Ther. 2007, 321, 975-982 (Pubitemid 46762690)
52. 2 receptor do not affect the species-selective activity of guanidine-type agonists Naunyn-Schmiedeberg's Arch. Pharmacol. 2007, 376, 253-264 (Pubitemid 50002453)
53. Neubig, R. R.; Spedding, M.; Kenakin, T.; Christopoulos, A. International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification. XXXVIII. Update on terms and symbols in quantitative pharmacology Pharmacol. Rev. 2003, 55, 597-606 (Pubitemid 37500521)
54. Cheng, Y.; Prusoff, W. H. Relationship between the inhibition constant (K1) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction Biochem. Pharmacol. 1973, 22, 3099-3108
55. 2-receptors J. Pharmacol. Exp. Ther. 2006, 317, 1262-1268 (Pubitemid 43764132)
56. Klinker, J. F.; Hagelüken, A.; Grünbaum, L.; Heilmann, I.; Nürnberg, B.; Harhammer, R.; Offermanns, S.; Schwaner, I.; Ervens, J.; Wenzel-Seifert, K.; Müller, T.; Seifert, R. Mastoparan may activate GTP hydrolysis by Gi-proteins in HL-60 membranes indirectly through interaction with nucleoside diphosphate kinase Biochem. J. 1994, 304 (Part 2) 377-383 (Pubitemid 24368214)
57. Hagelüken, A. G., L.; Klinker, J. F.; Nürnberg, B.; Harhammer, R.; Schultz, G.; Leschke, C.; Schunack, W.; Seifert, R. Histamine receptor-dependent and/or -independent activation of guanine nucleotide-binding by histamine and 2-substituted histamine derivatives in human leukemia (HL-60) and human erythroleukemia (HEL) cells Biochem. Pharmacol. 1995, 49, 901-914
58. Seifert, R.; Hagelüken, A.; Hoer, A.; Hoer, D.; Grünbaum, L.; Offermanns, S.; Schwaner, I.; Zingel, V.; Schunack, W.; Schultz, G. The H1 receptor agonist 2-(3-chlorophenyl)histamine activates Gi proteins in HL-60 cells through a mechanism that is independent of known histamine receptor subtypes Mol. Pharmacol. 1994, 45, 578-586
59. 2 receptors J. Pharmacol. Exp. Ther. 2007, 321, 983-995 (Pubitemid 46762691)
60. 2 receptor. I. Theoretical investigations of histamine binding to an oligopeptide mimicking a part of the fifth transmembrane α-helix J. Comput.-Aided Mol. Des. 1996, 10, 461-478 (Pubitemid 126712441)
61. Messer, W. S., Jr. Bivalent ligands for G protein-coupled receptors Curr. Pharm. Des. 2004, 10, 2015-2020
62. Perez, M.; Pauwels, P. J.; Fourrier, C.; Chopin, P.; Valentin, J. P.; John, G. W.; Marien, M.; Halazy, S. Dimerization of sumatriptan as an efficient way to design a potent, centrally and orally active 5-HT1B agonist Bioorg. Med. Chem. Lett. 1998, 8, 675-680 (Pubitemid 28122373)
63. Shi, L.; Javitch, J. A. The binding site of aminergic G protein-coupled receptors: the transmembrane segments and second extracellular loop Annu. Rev. Pharmacol. Toxicol. 2002, 42, 437-467 (Pubitemid 34162546)
64. Kim, J.; Jiang, Q.; Glashofer, M.; Yehle, S.; Wess, J.; Jacobson, K. A. Glutamate residues in the second extracellular loop of the human A2a adenosine receptor are required for ligand recognition Mol. Pharmacol. 1996, 49, 683-691
65. 3 muscarinic acetylcholine receptor activation J. Biol. Chem. 2007, 282, 7385-7396 (Pubitemid 47093690)
66. Rasmussen, S. G. F.; Choi, H. J.; Fung, J. J.; Pardon, E.; Casarosa, P.; Chae, P. S.; DeVree, B. T.; Rosenbaum, D. M.; Thian, F. S.; Kobilka, T. S.; Schnapp, A.; Konetzki, I.; Sunahara, R. K.; Gellman, S. H.; Pautsch, A.; Steyaert, J.; Weis, W. I.; Kobilka, B. K. Structure of a nanobody-stabilized active state of the beta(2) adrenoceptor Nature 2011, 469, 175-180
67. Rasmussen, S. G. F.; Choi, H.-J.; Rosenbaum, D. M.; Kobilka, T. S.; Thian, F. S.; Edwards, P. C.; Burghammer, M.; Ratnala, V. R. P.; Sanishvili, R.; Fischetti, R. F.; Schertler, G. F. X.; Weis, W. I.; Kobilka, B. K. Crystal structure of the human β2 adrenergic G-protein-coupled receptor Nature 2007, 450, 383-387 (Pubitemid 350126755)
68. Warne, T.; Moukhametzianov, R.; Baker, J. G.; Nehme, R.; Edwards, P. C.; Leslie, A. G. W.; Schertler, G. F. X.; Tate, C. G. The structural basis for agonist and partial agonist action on a beta(1)-adrenergic receptor Nature 2011, 469, 241-244
69. Ghorai, P.; Kraus, A.; Birnkammer, T.; Geyer, R.; Bernhardt, G.; Dove, S.; Seifert, R.; Elz, S.; Buschauer, A. Chiral NG-acylated hetarylpropylguanidine-type histamine H2 receptor agonists do not show significant stereoselectivity Bioorg. Med. Chem. Lett. 2010, 20, 3173-3176
70. Igel, P.; Schnell, D.; Bernhardt, G.; Seifert, R.; Buschauer, A. Tritium-labeled N (1)-[3-(1 H -imidazol-4-yl)propyl]- N (2)-propionylguanidine ([(3) H ]UR-PI294), a high-affinity histamine H(3) and H(4) receptor radioligand ChemMedChem 2009, 4, 225-231
71. Iso, Y.; Shindo, H.; Hamana, H. Efficient synthesis of resin-bound a-TMSdiazoketones and their use in solid-phase organic synthesis Tetrahedron 2000, 56, 5353-5361 (Pubitemid 30637422)
72. Walseth, T. F.; Johnson, R. A. The enzymatic preparation of [alpha-(32)P]nucleoside triphosphates, cyclic [32P] AMP, and cyclic [32P] GMP Biochim. Biophys. Acta 1979, 562, 11-31
73. Seifert, R. L., T. W.; Lam, V. T.; Kobilka, B. K. Eur. J. Biochem. 1998, 255, 369-382
74. G-acylated imidazolylpropylguanidines J. Pharmacol. Exp. Ther. 2006, 317, 139-146
75. Asano, T.; Pedersen, S. E.; Scott, C. W.; Ross, E. M. Reconstitution of catecholamine-stimulated binding of guanosine 5′- O -(3-thiotriphosphate) to the stimulatory GTP-binding protein of adenylate cyclase Biochemistry 1984, 23, 5460-5467 (Pubitemid 15179576)
76. Hilf, G.; Gierschik, P.; Jakobs, K. H. Muscarinic acetylcholine receptor-stimulated binding of guanosine 5′- O -(3-thiotriphosphate) to guanine-nucleotide-binding proteins in cardiac membranes Eur. J. Biochem. 1989, 186, 725-731 (Pubitemid 20030128)