Structural modifications of UMP, UDP, and UTP leading to subtype-selective agonists for P2Y2, P2Y4, and P2Y6 receptors

Journal of Medicinal Chemistry

Volumn 54, Issue 8, 2011, Pages 2878-2890

  El Tayeb, Ali ^a,c   Qi, Aidong ^b   Nicholas, Robert A ^b   Müller, Christa E ^a  

^a UNIVERSITY OF BONN   (Germany)

^b UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

^c AL AZHAR UNIVERSITY   (Egypt)

Author keywords

[No Author keywords available]

Indexed keywords

2 PHENYLTHIOURIDINE MONOPHOSPHATE; 3 PHENACYL 5' URIDYLIC ACID (1,1 CHLORO 1 PHOSPHONOMETHYL 1 PHOSPHONYL)ANHYDRIDE; 4 THIO 5' URIDYLIC ACID (1,1 DIFLUORO 1 PHOSPHONOMETHYL 1 PHOSPHONYL)ANHYDRIDE; ALKYL GROUP; CARBENE; FLUORINE DERIVATIVE; PURINERGIC P2Y2 RECEPTOR; PURINERGIC P2Y4 RECEPTOR; PURINERGIC P2Y6 RECEPTOR; PURINERGIC RECEPTOR STIMULATING AGENT; UNCLASSIFIED DRUG; URIDINE DIPHOSPHATE; URIDINE PHOSPHATE; URIDINE TRIPHOSPHATE;

ARTICLE; CHEMICAL MODIFICATION; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SCREENING; DRUG SELECTIVITY; DRUG SYNTHESIS; HUMAN; HUMAN CELL; STRUCTURE ACTIVITY RELATION;

CHROMATOGRAPHY, HIGH PRESSURE LIQUID; MAGNETIC RESONANCE SPECTROSCOPY; NUCLEIC ACID CONFORMATION; PURINERGIC AGONISTS; SPECTROMETRY, MASS, ELECTROSPRAY IONIZATION; URACIL NUCLEOTIDES;

EID: 79955450612     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm1016297     Document Type: Article

References (48)

1. Burnstock, G. Purine and pyrimidine receptors Cell. Mol. Life Sci. 2007, 12, 1471-1483 (Pubitemid 46954150)
2. Borrmann, T.; Abdelrahman, A.; Volpini, R.; Lambertucci, C.; Alksnis, E.; Gorzalka, S.; Knospe, M.; Schiedel, A. C.; Cristalli, G.; Müller, C. E. Structure-activity relationships of adenine and deazaadenine derivatives as ligands for adenine receptors, a new purinergic receptor family J. Med. Chem. 2009, 52, 5974-5989
3. i protein-coupled receptor for adenine from mouse brain Mol. Pharmacol. 2008, 73, 469-477 (Pubitemid 351159217)
4. Abbracchio, M. P.; Burnstock, G.; Boeynaems, J. M.; Barnard, E. A.; Boyer, J. L.; Kennedy, C.; Knight, G. E.; Fumagalli, M.; Gachet, C.; Jacobson, K. A.; Weisman, G. A. International Union of Pharmacology LVIII: update on the P2Y G protein-coupled nucleotide receptors: From molecular mechanisms and pathophysiology to therapy Pharmacol. Rev. 2006, 58, 281
5. von Kügelgen, I.; Wetter, A. Molecular pharmacology of P2Y-receptors Naunyn Schmiedeberg's Arch. Pharmacol. 2000, 362, 310-323
6. Brunschweiger, A.; Müller, C. E. P2 Receptors activated by uracil nucleotides-An update Curr. Med. Chem. 2006, 13, 289-312
7. 2 purinergic receptor Drug Dev. Res. 1996, 37, 133 abstract
8. Jacobson, K. A.; Ivanov, A. A.; de Castro, S.; Harden, T. K.; Ko, H. Development of selective agonists and antagonists of P2Y receptors Purinergic Signalling 2009, 5, 75-89
9. Burnstock, G. Pathophysiology and therapeutical potential of purinergic signaling Pharmacol. Rev. 2006, 58, 58-86
10. Ueno, M.; Ferreiro, J. L.; Angiolillo, D. J. Update on the clinical development of cangrelor Expert Rev. Cardiovasc. Ther. 2010, 8, 1069-1077
11. 2 receptor agonist for the treatment of cystic fibrosis J. Pharmacol. Exp. Ther. 2002, 302, 871-880 (Pubitemid 34920206)
12. Pendergast, W.; Yerxa, B. R.; Douglass, J. G.; Shaver, S. R.; Dougherty, R. W.; Redick, C. C.; Sims, I. F.; Rideout, J. L. Synthesis and P2Y receptor activity of a series of uridine dinucleoside 5′-Polyphosphates Bioorg. Med. Chem. Lett. 2001, 11, 157-160 (Pubitemid 32099630)
13. Shaver, S. R.; Rideout, J. L.; Pendergast, W.; Douglass, J. G.; Brown, E. G.; Boyer, J. L.; Patel, R. I.; Redick, C. C.; Jones, A. C.; Picher, M.; Yerxa, B. R. Structure-activity relationships of dinucleotides: Potent and selective agonists of P2Y receptors Purinergic Signalling 2005, 1, 183-191 (Pubitemid 40466903)
14. 2 receptor agonist: results of a phase 1/phase 2 multicenter study in mild to moderate cystic fibrosis Pediatr. Pulmonol. 2005, 39, 339-348 (Pubitemid 40411534)
15. Tauber, J.; Davitt, W. F.; Bokosky, J. E.; Nichols, K. K.; Yerxa, B. R.; Schaberg, A. E.; LaVange, L. M.; Mills-Wilson, M. C.; Kellerman, D. J. Double-masked, placebo-controlled safety and efficacy trial of diquafosol tetrasodium (INS365) ophthalmic solution for the treatment of dry eye Cornea 2004, 23, 784-792 (Pubitemid 39447308)
16. 2 receptor agonist for the treatment of cystic fibrosis. (Abstract in Purines 2010: Adenine Nucleosides and Nucleotides in Biomedicine) Purinergic Signalling 2010, 16.
17. Santen and Inspire Announce Approval of DIQUAS for Dry Eye Treatment in Japan, http://ir.inspirepharm.com and www.santen.com. April 16, 2010.
18. 2 receptor antagonists Bioorg. Med. Chem. 2009, 17, 5071-5079
19. Cosyn, L.; Van Calenbergh, S.; Joshi, B. V.; Ko, H.; Carter, R. L.; Harden, T. K.; Jacobson, K. A. Synthesis and P2Y receptor activity of nucleoside 5′-phosphonate derivatives Bioorg. Med. Chem. Lett. 2009, 19, 3002-3005
20. 6 receptors J. Med. Chem. 2006, 49, 7076-7087 (Pubitemid 44885995)
21. 6 receptor: molecular modeling leads to the rational design of a novel agonist based on a unique conformational preference J. Med. Chem. 2005, 48, 8108-8111 (Pubitemid 43032518)
22. 2 receptor agonists Eur. J. Med. Chem. 1999, 34, 809-824 (Pubitemid 29533849)
23. 4 receptors Biochem. Pharmacol. 2006, 71, 540-549 (Pubitemid 43077087)
24. 6-receptor agonist J. Med. Chem. 2010, 53, 1673-1685
25. Maruoka, H.; Barrett, M. O.; Ko, H.; Tosh, D. K.; Melman, A.; Burianek, L. E.; Balasubramanian, R.; Berk, B.; Costanzi, S.; Harden, T. K.; Jacobson, K. A. Pyrimidine ribonucleotides with enhanced selectivity as P2Y(6) receptor agonists: novel 4-alkyloxyimino, (S)-methanocarba, and 5′-triphosphate gamma-ester modifications J. Med. Chem. 2010, 53, 4488-4501
26. 2 receptor and design of a selective agonist, 2′-amino-2′-deoxy-2-thiouridine 5′-triphosphate J. Med. Chem. 2007, 50, 1166-1176 (Pubitemid 46496317)
27. Hilbert, G. E.; Johnson, T. B. Research on pyrimidines CXVII. A method for the synthesis of nucleosides J. Am. Chem. Soc. 1930, 4489-4494
28. Dunkel, M.; Cook, D.; Acevedo, L. O. Synthesis of novel C-2 substituted pyrimidine nucleoside analogs J. Heterocycl. Chem. 1993, 30, 1421-1430 (Pubitemid 24035853)
29. Abdel-Rahman, A. A.-H.; Zahran, M. A.; Abdel-Megeid, A. E.-S.; Pedersen, E. B.; Nielsen, C. Synthesis of S2-alkyl-2-thiouridines Synthesis 1996, 2, 237-241
30. 5S Z. Kristallogr.-New Cryst. Struct. 2009, 224, 107-108
31. Laduree, D.; Fossey, C.; Delbederi, Z.; Sugeac, E.; Schmidt, S.; Laumond, G.; Aubertin, A.-M. Synthesis and antiviral activity of aryl phosphoramidate derivatives of β- d-and β- l -C-5-substituted 2′,3′- didehydro-2′,3′-dideoxy-uridine bearing linker arms J. Enzyme Inhib. Med. Chem. 2005, 20, 533-549 (Pubitemid 43994751)
32. Griffon, J.-F.; Mathe, C.; Faraj, A.; Aubertin, A.-M.; De Clercq, E.; Balzarini, J.; Sommadossi, J.-P.; Gosselin, G. Stereospecific synthesis and biological evaluations of β- l -pentofuranonucleoside derivatives of 5-fluorouracil and 5-fluorocytosine Eur. J. Med. Chem. 2001, 36, 447-460 (Pubitemid 32635216)
33. Kimura, T.; Miki, M.; Watanabe, K.; Kondo, S.; Ho, I. K.; Yamamoto, I. Metabolism of a novel hypnotic, N3-phenacyluridine, and hypnotic and sedative activities of its enantiomer metabolites in mouse Xenobiotica 2000, 30, 643-653 (Pubitemid 30449573)
34. Ludwig, J. A new route to nucleoside 5′-triphosphates Acta Biochim. Biophys. Acad. Sci. Hung. 1981, 16, 131-133
35. 12 receptors Bioorg. Med. Chem. Lett. 2005, 15, 5450-5452 (Pubitemid 41562968)
36. Wang, G.; Boyle, N.; Chen, F.; Rajappan, V.; Fagan, P.; Brooks, J. L.; Hurd, T.; Leeds, J. M.; Rajwanshi, V. R.; Jin, Y.; Prhavc, M.; Bruice, T. W.; Cook, P. D. Synthesis of AZT 5′-triphosphate mimics and their inhibitory effects on HIV-1 reverse transcriptase J. Med. Chem. 2004, 47, 6902-6913 (Pubitemid 40053778)
37. Ingall, A. H.; Dixon, J.; Bailey, A.; Coombs, M. E.; Cox, D.; McInally, I. J.; Hunt, S. F.; Kindon, N. D.; Teobald, B. J.; Willis, P. A.; Humphries, R. G.; Leff, P.; Clegg, J. A.; Smith, J. A.; Tomlinson, W. Antagonists of the platelet P2T receptor: A novel approach to antithrombotic therapy J. Med. Chem. 1999, 42, 213-220 (Pubitemid 29069856)
38. 1 receptor agonists Eur. J. Med. Chem. 2009, 44, 1525-1536
39. Brandish, P. E.; Hill, L. A.; Zheng, W.; Scolnick, E. M. Scintillation proximity assay of inositol phosphates in cell extracts: high-throughput measurement of G-protein-coupled receptor activation Anal. Biochem. 2003, 33, 311-318 (Pubitemid 36259956)
40. Lazarowski, E. R.; Watt, W. C.; Stutts, M. J.; Boucher, R. C.; Harden, T. K. Pharmacological selectivity of the cloned human P2U-purinoceptor: Potent activation by diadenosine tetraphosphate Br. J. Pharmacol. 1995, 116, 1619-1627
41. Nguyen, T.; Erb, L.; Weisman, G. A.; Marchese, A.; Heng, H. H.; Garrad, R. C.; George, S. R.; Turner, J. T.; O'Dowd, B. F. Cloning, expression, and chromosomal localization of the human uridine nucleotide receptor gene J. Biol. Chem. 1995, 270, 30845-30848 (Pubitemid 26012163)
42. 6 receptor agonists Bioorg. Med. Chem. 2008, 16, 6319-6332 (Pubitemid 351790765)
43. 6 receptor Biochem. Biophys. Res. Commun. 1996, 222, 303-308 (Pubitemid 26335011)
44. Guile, S. D.; Ince, F.; Ingall, A. H.; Kindon, N. D.; Meghani, P.; Mortimore, M. P. The medicinal chemistry of the P2 receptor family Prog. Med. Chem. 2001, 38, 115-187
45. Hillmann, P.; Ko, G. Y.; Spinrath, A.; Raulf, A.; von Kügelgen, I.; Wolff, S. C.; Nicholas, R. A.; Kostenis, E.; Höltje, H. D.; Müller, C. E. Key determinants of nucleotide-activated G protein-coupled P2Y(2) receptor function revealed by chemical and pharmacological experiments, mutagenesis and homology modeling J. Med. Chem. 2009, 52, 2762-2775
46. Doerr, I. L.; Cushley, R. J.; Fox, J. J. Nucleosides. L. Synthesis of 2,3′-imino-1-(2-deoxy-β- d -threo-pentofuranosyl)thymine and related derivatives J. Org. Chem. 1968, 33, 1592-1599
47. Abdel-Rahman, A. A. H.; Pedersen, E. B.; Nielsen, C. Synthesis of 5-methylisocytidine derivatives Monatsh. Chem. 1996, 127, 455-459
48. Skaric, V.; Gaspert, B.; Hohnjec, M.; Lacan, G. Some dihydro-cytidines and isocytidines J. Chem. Soc., Perkin 1 1974, 2, 267-271