Pyrimidine nucleotides with 4-alkyloxyimino and terminal tetraphosphate δ-ester modifications as selective agonists of the P2Y4 receptor

Journal of Medicinal Chemistry

Volumn 54, Issue 12, 2011, Pages 4018-4033

  Maruoka, Hiroshi ^a   Jayasekara, M P Suresh ^a   Barrett, Matthew O ^b   Franklin, Derek A ^b   De Castro, Sonia ^a   Kim, Nathaniel ^a   Costanzi, Stefano ^c   Harden, T Kendall ^b   Jacobson, Kenneth A ^a  

^a NATIONAL INSTITUTES OF HEALTH   (United States)

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

^c NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYTIDINE DERIVATIVE; N4 BENZYLOXYCYTIDINE 5' TRIPHOSPHATE TRIETHYLAMMONIUM; N4 ETHOXYCYTIDINE 5' TRIPHOSPHATE TRIETHYLAMMONIUM; N4 METHOXYCYTIDINE 5' TRIPHOSPHATE TRIETHYLAMMONIUM; N4 PHENYLETHOXYCYTIDINE 5' TRIPHOSPHATE TRIETHYLAMMONIUM; N4 PHENYLPROPOXYCYTIDINE 5' TRIPHOSPHATE TRIETHYLAMMONIUM; N4 TERT BUTYLOXYCYTIDINE 5' TRIPHOSPHATE TRIETHYLAMMONIUM; P1 (N4 BENZYLOXYCYTIDINE 5') P4 (3' DEOXY 3' FLUOROGLUCOSE 1') TETRAPHOSPHATE TRIETHYLAMMONIUM; P1 (N4 METHOXYCYTIDINE 5') P4 (3' DEOXY 3' FLUOROGLUCOSE 1') TETRAPHOSPHATE TRIETHYLAMMONIUM; P1 (URIDINE 5') P4 (2' DEOXY 2' ACETAMIDOGLUCOSE 1') TETRAPHOSPHATE TRIETHYLAMMONIUM; P1 (URIDINE 5') P4 (2' DEOXY 2' FLUOROGLUCOSE 1') TETRAPHOSPHATE TRIETHYLAMMONIUM; P1 (URIDINE 5') P4 (3' DEOXY 3' FLUOROGLUCOSE 1') TETRAPHOSPHATE TRIETHYLAMMONIUM; P1 (URIDINE 5') P4 (GLUCURONIC ACID 1') TETRAPHOSPHATE TRIETHYLAMMONIUM; PHOSPHOLIPASE C; PURINERGIC P2Y4 RECEPTOR; PURINERGIC RECEPTOR STIMULATING AGENT; PYRIMIDINE NUCLEOTIDE; UNCLASSIFIED DRUG; UNINDEXED DRUG; URIDINE; URIDINE 5' (3 CHLOROPHENYL)TETRAPHOSPHATE TRIETHYLAMMONIUM; URIDINE 5' (3 METHOXYPHENYL)TETRAPHOSPHATE TRIETHYLAMMONIUM; URIDINE 5' (3 NITROPHENYL)TETRAPHOSPHATE TRIETHYLAMMONIUM; URIDINE 5' (4 CHLOROPHENYL)TETRAPHOSPHATE TRIETHYLAMMONIUM; URIDINE 5' (4 METHOXYPHENYL)TETRAPHOSPHATE TRIETHYLAMMONIUM; URIDINE 5' (4 NITROPHENYL)TETRAPHOSPHATE TRIETHYLAMMONIUM; URIDINE 5' ALLOSE 1' TETRAPHOSPHATE TRIETHYLAMMONIUM; URIDINE 5' BETA,GAMMA DICHLOROMETHYLENE TRIPHOSPHATE AMMONIUM; URIDINE 5' GLUCOSE 1' BETA,GAMMA DICHLOROMETHYLENE TETRAPHOSPHATE TRIETHYLAMMONIUM; URIDINE 5' MANNOSE 1' TETRAPHOSPHATE TRIETHYLAMMONIUM; URIDINE 5' XYLOSE 1' TETRAPHOSPHATE TRIETHYLAMMONIUM;

ARTICLE; ASTROCYTOMA CELL; CHEMICAL MODIFICATION; DRUG ACTIVITY; DRUG SYNTHESIS; ENZYME STABILITY; HUMAN; HUMAN CELL; HYDROGEN BOND; MOLECULAR DOCKING; MOLECULAR MODEL;

AMINO ACID SEQUENCE; CELL LINE, TUMOR; DRUG STABILITY; ESTERS; HUMANS; LIGANDS; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; PURINERGIC P2 RECEPTOR AGONISTS; RADIOLIGAND ASSAY; RECEPTORS, PURINERGIC P2; SEQUENCE HOMOLOGY, AMINO ACID; STRUCTURE-ACTIVITY RELATIONSHIP; URACIL NUCLEOTIDES;

EID: 79959465302     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm101591j     Document Type: Article

References (45)

1. Abbracchio, M. P.; Burnstock, G.; Boeynaems, J. M.; Barnard, E. A.; Boyer, J. L.; Kennedy, C.; Fumagalli, M.; King, B. F.; 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, 281-341 (Pubitemid 44394905)
2. Brunschweiger, A.; Müller, C. E. P2 Receptors activated by uracil nucleotides - An update Curr. Med. Chem. 2006, 13, 289-312
3. Nicholas, R. A.; Lazarowski, E. R.; Watt, W. C.; Li, Q.; Harden, T. K. Uridine nucleotide selectivity of three phospholipase C-activating P2 receptors: Identification of a UDP-selective, a UTP-selective, and an ATP- and UTP-specific receptor Mol. Pharmacol. 1996, 50, 224-229 (Pubitemid 26265124)
4. 4 receptor Eur. J. Pharmacol. 1996, 317, 383-389 (Pubitemid 27014046)
5. 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)
6. 2 receptor agonist for the treatment of cystic fibrosis J. Pharmacol. Exp. Ther. 2002, 302, 871-880 (Pubitemid 34920206)
7. 2 agonists that led to Phase 3 Pulm. Pharmacol. Ther. 2008, 21, 600-607 (Pubitemid 351970709)
8. 4 receptors Biochem. Pharmacol. 2006, 71, 540-549 (Pubitemid 43077087)
9. 2 agonists with enhanced stability over UTP Bioorg. Med. Chem. Lett. 2007, 17, 558-561 (Pubitemid 46098926)
10. Ivanov, A.; Ko, H.; Cosyn, L.; Maddileti, S.; Besada, P.; Fricks, I.; Costanzi, S.; Harden, T.; Calenbergh, S.; Jacobson, K. Molecular modeling of the human P2Y2 receptor and design of a selective agonist, 2′-amino-2′- deoxy-2-thiouridine 5′-triphosphate J. Med. Chem. 2007, 50, 1166-1176 (Pubitemid 46496317)
11. 6 receptors J. Med. Chem. 2002, 45, 208-218 (Pubitemid 34038555)
12. 6 Receptors J. Med. Chem. 2006, 49, 7076-7087 (Pubitemid 44885995)
13. 6 receptor agonists Bioorg. Med. Chem. 2008, 16, 6319-6332 (Pubitemid 351790765)
14. 2 receptor antagonists Bioorg. Med. Chem. 2009, 17, 5071-5079
15. 6 Receptor Agonists: Novel 4-Alkyloxyimino, (S)-Methanocarba, and 5′-Triphosphate γ-Ester Modifications J. Med. Chem. 2010, 53, 4488-4501
16. Wu, B.; Chien, E. Y.; Mol, C. D.; Fenalti, G.; Liu, W.; Katritch, V.; Abagyan, R.; Brooun, A.; Wells, P.; Bi, F. C.; Hamel, D. J.; Kuhn, P.; Handel, T. M.; Cherezov, V.; Stevens, R. C. Structures of the CXCR4 chemokine GPCR with small-molecule and cyclic peptide antagonists Science 2010, 330, 1066-1071
17. Kogo, S.; Yamada, K.; Iwai, Y.; Osawa, K.; Hayakawa, H. Process for Producing Di(pyrimidine nucleoside 5′-)polyphosphate. WO2008/012949 A1, 2008.
18. Heeres, A.; van Doren, H. A.; Gotlieb, K. F.; Bleeker, I. P. Synthesis of α- and β- D-glucopyranuronate 1-phosphate and α-D- glucopyranuronate 1-fluoride: Intermediates in the synthesis of D-glucuronic acid from starch Carbohydr. Res. 1997, 299, 221-227 (Pubitemid 27193259)
19. Bourdon, D. M.; Wing, M. R.; Edwards, E. B.; Sondek, J.; Harden, T. K. Quantification of isozyme-specific activation of phospholipase C-β 2 by Rac GTPases and phospholipase C-Iu by Rho GTPases in an intact cell assay system Methods Enzymol. 2006, 406, 489-499 (Pubitemid 43207462)
20. Costanzi, S.; Mamedova, L.; Gao, Z.; Jacobson, K. Architecture of P2Y nucleotide receptors: structural comparison based on sequence analysis, mutagenesis, and homology modeling J. Med. Chem. 2004, 47, 5393-5404 (Pubitemid 39382789)
21. 1 receptor antagonists: 2-alkynyl (N)-methanocarba 2′-deoxyadenosine 3′,5′-bisphosphate analogues and conjugation to a polyamidoamine (PAMAM) dendrimer carrier Bioconjugate Chem. 2010, 21, 1190-205
22. 1 receptor in surface expression and activation processes J. Biol. Chem. 1999, 274, 14639-14647
23. 1 receptor Biochemistry 1999, 38, 3498-3507
24. 2 receptor function revealed by chemical and pharmacological experiments, mutagenesis and homology modeling J. Med. Chem. 2009, 52, 2762-2775
25. 1 receptor: molecular modeling and site-directed mutagenesis as tools to identify agonist and antagonist recognition sites J. Med. Chem. 1998, 41, 1456-66 (Pubitemid 28198975)
26. 1 receptor Mol. Pharmacol. 1997, 52, 499-507 (Pubitemid 27412976)
27. 4-methoxycytosine Acta Crystallogr. 1991, C47, 2635-2637
28. Ballesteros, J. A.; Weinstein, H. Integrated methods for the construction of three-dimensional models and computational probing of structure-function relations in G protein-coupled receptors. In Methods in Neurosciences; Stuart, C. S., Ed.; Academic Press: San Diego, 1995; Vol. 25, pp 366-428.
29. van Rhee, A. M.; Jacobson, K. A. Molecular architecture of G protein-coupled receptors Drug Dev. Res. 1996, 37, 1-38 (Pubitemid 26106319)
30. 1 antagonists: Combining receptor-based modeling and QSAR for a quantitative prediction of the biological activity based on consensus scoring J. Med. Chem. 2007, 50, 3229-3241 (Pubitemid 47065972)
31. Yitzhaki, S.; Shneyvais, V.; Jacobson, K. A.; Shainberg, A. Involvement of uracil nucleotides in protection of cardiomyocytes from hypoxic stress Biochem. Pharmacol. 2005, 69, 1215-1223 (Pubitemid 40417493)
32. 2+ ions Br. J. Pharmacol. 2003, 140, 1177-1186 (Pubitemid 38117421)
33. 4-null mice Mol. Pharmacol. 2003, 63, 777-783 (Pubitemid 36368983)
34. 4 receptors in the regulation of intestinal chloride secretion Br. J. Pharmacol. 2005, 146, 364-369 (Pubitemid 41486678)
35. 2 receptors Pflugers Arch. 2007, 454, 977-987 (Pubitemid 47338455)
36. Cosentino, S.; Barcella, S.; Lo, H.; Burbiel, J. C.; Müller, C. E.; Tremoli, E.; Banfi, C.; Abbracchio, M. P. Role of P2 receptors in a cardiomyocyte ischemic hypoxia model. Purines2010, Tarragona, Spain. May 30-June 2, 2010. Abstract P10-11.
37. 4 receptor in inflammation and angiogenesis. Purines 2008 Meeting June 29-July 2, 2008, Copenhagen, Denmark. Purinergic Signalling 2008, 4 (Suppl. 1), 118.
38. 2 receptor regulates VCAM-1 membrane and soluble forms and eosinophil accumulation during lung inflammation J. Immunol. 2010, 185, 3702-3707
39. MacDonald, D. L. [11] Chemical synthesis of aldose 1-phosphates Methods Enzymol. 1966, 8, 121-125
40. The Molecular Operating Environment (MOE); Chemical Computing Group, Inc.: Montreal, Canada, 2009; Vol. 10; www.ccg.com.
41. 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
42. Maestro, 9.1; Schrodinger, LLC: New York, NY; www.schrodinger.com.
43. MacroModel, 9.8; Schrodinger, LLC: New York, NY; www.schrodinger.com.
44. SiteMap, 2.4; Schrödinger, LLC: New York, NY; www.schrodinger.com.
45. Bradford, M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein dye binding Anal. Biochem. 1976, 76, 248-254