Hybrid ortho/allosteric ligands for the adenosine A1 receptor

Journal of Medicinal Chemistry

Volumn 53, Issue 8, 2010, Pages 3028-3037

  Narlawar, Rajeshwar ^a   Lane, J Robert ^a   Doddareddy, Munikumar ^a   Lin, Judy ^a   Brussee, Johannes ^a   Ijzerman, Adriaan P ^a  

^a LEIDEN UNIVERSITY   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

2 AMINO 4,5 DIMETHYL 3 (3 TRIFLUOROMETHYLBENZOYL)THIOPHENE; ADENOSINE A1 RECEPTOR; ADENOSINE A1 RECEPTOR AGONIST; G PROTEIN COUPLED RECEPTOR; LUF 6258; N6 [2 AMINO 3 (3,4 DICHLOROBENZOYL) 4,5,6,7 TETRAHYDROTHIENO[2,3 C]PYRIDIN 6 YL 9 NONYLOXY 4 PHENYL]ADENOSINE; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; CONTROLLED STUDY; DRUG POTENCY; DRUG SYNTHESIS; HUMAN; MOLECULAR MODEL; NONHUMAN; RECEPTOR AFFINITY;

ADENOSINE; ALLOSTERIC SITE; ANIMALS; BINDING, COMPETITIVE; CHO CELLS; CRICETINAE; CRICETULUS; HUMANS; LIGANDS; MITOGEN-ACTIVATED PROTEIN KINASE 1; MITOGEN-ACTIVATED PROTEIN KINASE 3; MODELS, MOLECULAR; PHOSPHORYLATION; RADIOLIGAND ASSAY; RECEPTOR, ADENOSINE A1; STRUCTURE-ACTIVITY RELATIONSHIP; THIOPHENES;

EID: 77951136172     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm901252a     Document Type: Article

References (41)

1. Ma, P.; Zemmel, R. Value of novelty? Nat. Rev. Drug Discovery 2002, 1, 571-572
2. Overington, J. P.; Al-Lazikani, B.; Hopkins, A. L. How many drug targets are there? Nat. Rev. Drug Discovery 2006, 5, 993-996
3. Ralevic, V.; Burnstock, G. Receptors for purines and pyrimidines Pharmacol. Rev. 1998, 50, 413-492
4. Fredholm, B. B.; IJzerman, A. P.; Jacobson, K. A.; Klotz, K. N.; Linden, J. International Union of Pharmacology. XXV. Nomenclature and classification of adenosine receptors Pharmacol. Rev. 2001, 53, 527-552
5. May, L. T.; Leach, K.; Sexton, P. M.; Christopoulos, A. Allosteric modulation of G protein-coupled receptors Annu. Rev. Pharmacol. Toxicol. 2007, 47, 1-51
6. Christopoulos, A. Allosteric binding sites on cell-surface receptors: novel targets for drug discovery Nat. Rev. Drug Discovery 2002, 1, 198-210
7. Soudijn, W.; Van Wijngaarden, I.; IJzerman, A. P. Allosteric modulation of G protein-coupled receptors: perspectives and recent developments Drug Discovery Today 2004, 9, 752-758
8. Gao, Z. G.; Jacobson, K. A. Allosterism in membrane receptors Drug Discovery Today 2006, 11, 191-202
9. Valant, C.; Sexton, P. M.; Christopoulos, A. Orthosteric/allosteric bitopic ligands: going hybrid at GPCRs Mol. Interv. 2009, 9, 125-135
10. Valant, C.; Gregory, K. J.; Hall, N. E.; Scammells, P. J.; Lew, M. J.; Sexton, P. M.; Christopoulos, A. A novel mechanism of G protein-coupled receptor functional selectivity. Muscarinic partial agonist McN-A-343 as a bitopic orthosteric/allosteric ligand J. Biol. Chem. 2008, 283, 29312-29321
11. 2 muscarinic receptor Mol. Pharmacol. 2007, 72, 291-302
12. Antony, J.; Kellershohn, K.; Mohr-Andra, M.; Kebig, A.; Prilla, S.; Muth, M.; Heller, E.; Disingrini, T.; Dallanoce, C.; Bertoni, S.; Schrobang, J.; Trankle, C.; Kostenis, E.; Christopoulos, A.; Holtje, H. D.; Barocelli, E.; De Amici, M.; Holzgrabe, U.; Mohr, K. Dualsteric GPCR targeting: a novel route to binding and signaling pathway selectivity FASEB J. 2009, 23, 442-450
13. Disingrini, T.; Muth, M.; Dallanoce, C.; Barocelli, E.; Bertoni, S.; Kellershohn, K.; Mohr, K.; De Amici, M.; Holzgrabe, U. Design, synthesis, and action of oxotremorine-related hybrid-type allosteric modulators of muscarinic acetylcholine receptors J. Med. Chem. 2006, 49, 366-372
14. Portoghese, P. S.; Larson, D. L.; Sayre, L. M.; Yim, C. B.; Ronsisvalle, G.; Tam, S. W.; Takemori, A. E. Opioid agonist and antagonist bivalent ligands. The relationship between spacer length and selectivity at multiple opioid receptors J. Med. Chem. 1986, 29, 1855-1861
15. 1B/1D receptor subtypes Bioorg. Med. Chem. Lett. 1998, 8, 1407-1412
16. 1B/1D agonists J. Med. Chem. 1996, 39, 4920-4927
17. Bhushan, R. G.; Sharma, S. K.; Xie, Z.; Daniels, D. J.; Portoghese, P. S. A bivalent ligand (KDN-21) reveals spinal delta and kappa opioid receptors are organized as heterodimers that give rise to delta(1) and kappa(2) phenotypes. Selective targeting of delta-kappa heterodimers J. Med. Chem. 2004, 47, 2969-2972
18. Portoghese, P. S.; Larson, D. L.; Yim, C. B.; Sayre, L. M.; Ronsisvalle, G.; Lipkowski, A. W.; Takemori, A. E.; Rice, K. C.; Tam, S. W. Stereostructure-activity relationship of opioid agonist and antagonist bivalent ligands. Evidence for bridging between vicinal opioid receptors J. Med. Chem. 1985, 28, 1140-1141
19. Kramer, R. H.; Karpen, J. W. Spanning binding sites on allosteric proteins with polymer-linked ligand dimers Nature 1998, 395, 710-713
20. 3 adenosine receptor agonists J. Biol. Chem. 2000, 275, 30272-30279
21. s Biochem. J. 2006, 396, 139-146
22. 1 receptor Eur. J. Pharmacol. 2005, 510, 1-8
23. 1 receptor Biochem. Pharmacol. 2001, 61, 137-144
24. 1 adenosine receptor: influences of acidic and hydroxy residues in the first four transmembrane domains on ligand binding Mol. Pharmacol. 1996, 50, 1635-1642
25. 1 receptor allosteric modulators and antagonists J. Med. Chem. 2008, 51, 6165-6172
26. 1-receptor agonists that allow quantification of ligand-receptor interactions in microdomains of single living cells J. Med. Chem. 2007, 50, 782-793
27. 1 adenosine receptor J. Med. Chem. 1991, 34, 2877-2882
28. 1 receptor binding and function by 2-amino-3-benzoylthiophenes Mol. Pharmacol. 1990, 38, 939-949
29. 1 receptor binding by 2-amino-3- benzoylthiophenes Mol. Pharmacol. 1990, 38, 950-958
30. 1 receptor. Synthesis and biological evaluation of novel 2-amino-3-benzoylthiophenes as allosteric enhancers of agonist binding J. Med. Chem. 1999, 42, 3629-3635
31. 1 receptor ligands J. Med. Chem. 2008, 51, 6128-6137
32. Xie, Z.; Bhushan, R. G.; Daniels, D. J.; Portoghese, P. S. Interaction of bivalent ligand KDN21 with heterodimeric delta-kappa opioid receptors in human embryonic kidney 293 cells Mol. Pharmacol. 2005, 68, 1079-1086
33. 1 receptor coupling to G-proteins in brain J. Neurochem. 2005, 93, 715-723
34. 1 adenosine receptors increase receptor-G protein coupling and counteract Guanine nucleotide effects on agonist binding Mol. Pharmacol. 2003, 64, 1557-1564
35. 1 receptor J. Pharmacol. Exp. Ther. 1997, 281, 761-768
36. Avlani, V. A.; Gregory, K. J.; Morton, C. J.; Parker, M. W.; Sexton, P. M.; Christopoulos, A. Critical role for the second extracellular loop in the binding of both orthosteric and allosteric G protein-coupled receptor ligands J. Biol. Chem. 2007, 282, 25677-25686
37. 2A adenosine receptor bound to an antagonist Science 2008, 322, 1211-1217
38. Molecular Operating Environment (MOE 2008.10); Chemical Computing Group, Inc.; Quebec, Canada.
39. Wang, J. M.; Cieplak, P.; Kollman, P. A. How well does a restrained electrostatic potential (RESP) model perform in calculating conformational energies of organic and biological molecules? J. Comput. Chem. 2000, 21, 1049-1074
40. Labute, P. The generalized Born/volume integral implicit solvent model: Estimation of the free energy of hydration using London dispersion instead of atomic surface area J. Comput. Chem. 2008, 29, 1693-1698
41. Lovell, S. C.; Davis, I. W.; Adrendall, W. B.; de Bakker, P. I. W.; Word, J. M.; Prisant, M. G.; Richardson, J. S.; Richardson, D. C. Structure validation by C alpha geometry: phi,psi and C beta deviation Proteins: Struct. Funct. Bioinf. 2003, 50, 437-450