Scaffold decoration at positions 5 and 8 of 1,2,4-triazolo[1,5- c ]pyrimidines to explore the antagonist profiling on adenosine receptors: A preliminary structure-activity relationship study

Journal of Medicinal Chemistry

Volumn 57, Issue 14, 2014, Pages 6210-6225

  Federico, Stephanie ^a   Ciancetta, Antonella ^b   Porta, Nicola ^b   Redenti, Sara ^a   Pastorin, Giorgia ^c   Cacciari, Barbara ^d   Klotz, Karl Norbert ^e   Moro, Stefano ^b   Spalluto, Giampiero ^a  

^a UNIVERSITY OF TRIESTE   (Italy)

^b UNIVERSITY OF PADOVA   (Italy)

^c NATIONAL UNIVERSITY OF SINGAPORE   (Singapore)

^d UNIVERSITY OF FERRARA   (Italy)

^e UNIVERSITY OF WÜRZBURG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

1,2,4 TRIAZOLO[1,5 C]PYRIMIDINE; 2 FURAN 2 YL 5 (2 METHOXY ETHYLAMINO) [1,2,4]TRIAZOLO[1,5 C]PYRIMIDINE 8 CARBOXYLIC ACID ETHYL ESTER; 2 FURAN 2 YL 5 (4 METHOXY BENZYLAMINO) [1,2,4]TRIAZOLO[1,5 C] PYRIMIDINE 8 CARBOXYLIC ACID ETHYL ESTER; 2 FURAN 2 YL 5 (4 METHYL BENZYLAMINO) [1,2,4]TRIAZOLO[1,5 C] PYRIMIDINE 8 CARBOXYLIC ACID ETHYL ESTER; 2 FURAN 2 YL 5 (4 TRIFLUOROMETHYL BENZYLAMINO) [1,2,4]TRIAZOLO [1,5 C]PYRIMIDINE 8 CARBOXYLIC ACID ETHYL ESTER; 2 FURAN 2 YL 5 ISOPROPYLAMINO [1,2,4]TRIAZOLO[1,5 C]PYRIMIDINE 8 CARBOXYLIC ACID ETHYL ESTER; 2 FURAN 2 YL 5 METHYLAMINO [1,2,4]TRIAZOLO[1,5 C]PYRIMIDINE 8 CARBOXYLIC ACID ETHYL ESTER; 2 FURAN 2 YL 5 PENTYLAMINO [1,2,4]TRIAZOLO[1,5 C]PYRIMIDINE 8 CARBOXYLIC ACID ETHYL ESTER; 2 FURAN 2 YL 5 PIPERIDIN 1 YL [1,2,4]TRIAZOLO[1,5 C]PYRIMIDINE 8 CARBOXYLIC ACID ETHYL ESTER; 2 FURAN 2 YL 5 PYRROLIDIN 1 YL [1,2,4]TRIAZOLO[1,5 C]PYRIMIDINE 8 CARBOXYLIC ACID ETHYL ESTER; 4 HYDROXY 2 METHYLTHIO 5 CARBETHOXYPYRIMIDINE SODIUM SALT; 4 [N' (FURAN 2 CARBONYL) HYDRAZINO] 2 METHYLSULFANYL PYRIMIDINE 5 CARBOXYLIC ACID ETHYL ESTER; 5 (2 ETHYL HEXYLAMINO) 2 FURAN 2 YL [1,2,4]TRIAZOLO[1,5 C] PYRIMIDINE 8 CARBOXYLIC ACID ETHYL ESTER; 5 (4 CHLORO BENZYLAMINO) 2 FURAN 2 YL [1,2,4]TRIAZOLO[1,5 C] PYRIMIDINE 8 CARBOXYLIC ACID ETHYL ESTER; 5 (4 FLUORO BENZYLAMINO) 2 FURAN 2 YL [1,2,4]TRIAZOLO[1,5 C] PYRIMIDINE 8 CARBOXYLIC ACID ETHYL ESTER; 5 (BENZHYDRYL AMINO) 2 FURAN 2 YL [1,2,4]TRIAZOLO[1,5 C] PYRIMIDINE 8 CARBOXYLIC ACID ETHYL ESTER; 5 (CYCLOHEXYLMETHYLAMINO) 2 FURAN 2 YL [1,2,4]TRIAZOLO[1,5 C] PYRIMIDINE 8 CARBOXYLIC ACID ETHYL ESTER; 5 BENZYLAMINO 2 FURAN 2 YL [1,2,4]TRIAZOLO[1,5 C]PYRIMIDINE 8 CARBOXYLIC ACID ETHYL ESTER; 5 CYCLOBUTYLAMINO 2 FURAN 2 YL [1,2,4]TRIAZOLO[1,5 C]PYRIMIDINE 8 CARBOXYLIC ACID ETHYL ESTER; 5 CYCLOHEPTYLAMINO 2 FURAN 2 YL [1,2,4]TRIAZOLO[1,5 C]PYRIMIDINE 8 CARBOXYLIC ACID ETHYL ESTER; 5 CYCLOOCTYLAMINO 2 FURAN 2 YL [1,2,4]TRIAZOLO[1,5 C]PYRIMIDINE 8 CARBOXYLIC ACID ETHYL ESTER; 5 CYCLOPENTYLAMINO 2 FURAN 2 YL [1,2,4]TRIAZOLO[1,5 C] PYRIMIDINE 8 CARBOXYLIC ACID ETHYL ESTER; 5 CYCLOPROPYLAMINO 2 FURAN 2 YL [1,2,4]TRIAZOLO[1,5 C] PYRIMIDINE 8 CARBOXYLIC ACID ETHYL ESTER; 5 ETHYLAMINO 2 FURAN 2 YL [1,2,4]TRIAZOLO[1,5 C]PYRIMIDINE 8 CARBOXYLIC ACID ETHYL ESTER; 5 [(3,4 DIMETHOXYBENZYL)AMINO] 2 (FURAN 2 YL) [1,2,4]TRIAZOLO [1,5 C]PYRIMIDINE 8 CARBOXYLIC ACID ETHYL ESTER; 5 [(BIPHENYL 4 YLMETHYL) AMINO] 2 FURAN 2 YL [1,2,4]TRIAZOLO[1,5 C]PYRIMIDINE 8 CARBOXYLIC ACID ETHYL ESTER; ADENOSINE RECEPTOR BLOCKING AGENT; ETHYL 2 (FURAN 2 YL) 5 (METHYLTHIO) [1,2,4]TRIAZOLO[1,5 C] PYRIMIDINE 8 CARBOXYLATE; PYRIMIDINE DERIVATIVE; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ARTICLE; BINDING SITE; DRUG SYNTHESIS; HUMAN; HUMAN CELL; HYDROGEN BOND; ISOELECTRIC FOCUSING; MOLECULAR DOCKING; MOLECULAR MODEL; NUCLEOPHILICITY; PROTON NUCLEAR MAGNETIC RESONANCE; STATIC ELECTRICITY; STEREOSPECIFICITY; STRUCTURE ACTIVITY RELATION;

DOSE-RESPONSE RELATIONSHIP, DRUG; HUMANS; MODELS, MOLECULAR; MOLECULAR STRUCTURE; PURINERGIC P1 RECEPTOR ANTAGONISTS; PYRIMIDINES; RECEPTOR, ADENOSINE A2A; RECEPTOR, ADENOSINE A3; STRUCTURE-ACTIVITY RELATIONSHIP; TRIAZOLES;

EID: 84905053909     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm500752h     Document Type: Article

References (48)

1. Mustafa, S. J.; Morrison, R. R.; Teng, B.; Pelleg, A. Adenosine receptors and the heart: role in regulation of coronary blood flow and cardiac electrophysiology Handb. Exp. Pharmacol. 2009, 193, 161-188
2. Headrick, J. P.; Ashton, K. J.; Rosemeyer, R. B.; Peart, J. N. Cardiovascular adenosine receptors: expression, actions and interactions Pharmacol. Ther. 2013, 140, 92-111
3. Gomes, C. V.; Kaster, M. P.; Tomé, A. R.; Agostinho, P. M.; Cunha, R. A. Adenosine receptors and brain diseases: neuroprotection and neurodegeneration Biochim. Biophys. Acta 2011, 1808, 1380-1399
4. Stone, T. W.; Ceruti, S.; Abbracchio, M. P. Adenosine receptors and neurological disease: neuroprotection and neurodegeneration Handb. Exp. Pharmacol. 2009, 193, 535-587
5. Polosa, R.; Blackburn, M. R. Adenosine receptors as targets for therapeutic intervention in asthma and chronic obstructive pulmonary disease Trends Pharmacol. Sci. 2009, 30, 528-535
6. Wilson, C. N. Adenosine receptors and asthma in humans Br. J. Pharmacol. 2008, 155, 475-486
7. 2A receptors as drug target in Parkinson's disease CNS Neurol. Disord.: Drug Targets 2011, 10, 659-669
8. Chen, J. F.; Eltzschig, H. K.; Fredholm, B. B. Adenosine receptors as drug targets - what are the challenges? Nat. Rev. Drug Discovery 2013, 12, 265-286
9. Yan, L.; Burbiel, J. C.; Maass, A.; Muller, C. E. Adenosine receptor agonists: from basic medicinal chemistry to clinical development Expert Opin. Emerg. Drugs 2003, 8, 537-576
10. Fredholm, B. B. Adenosine receptors as targets for drug development Drug News Perspect. 2003, 16, 283-289
11. 3 adenosine receptor: a review of novel patented ligands Expert Opin. Ther. Pat. 2012, 22, 369-390
12. 2B receptor ligands: past, present and future trends Curr. Top. Med. Chem. 2010, 10, 923-940
13. 1 receptors ligands: past, present and future trends Curr. Top. Med. Chem. 2010, 10, 878-901
14. 1 modulators: a patent update (2008 to present) Expert Opin. Ther. Pat. 2013, 23, 355-367
15. 2A receptor as a drug discovery target J. Med. Chem. 2014, 57, 3623-3650
16. 3 adenosine receptor as multifaceted therapeutic target: pharmacology, medicinal chemistry, and in silico approaches Med. Res. Rev. 2013, 33, 235-335
17. Muller, C. E.; Jacobson, K. A. Recent developments in adenosine receptor ligands and their potential as novel drugs Biochim. Biophys. Acta 2011, 1808, 1290-159
18. 2A receptor system using positron emission tomography J. Med. Chem. 2000, 43, 4359-4362
19. 2A receptor antagonists preladenant and SCH 412348 [7-[2-[4-2,4-difluorophenyl]-1-piperazinyl]ethyl]-2-(2-furanyl)-7 H -pyrazolo[4,3- e ][1,2,4]triazolo[1,5- c ]pyrimidin-5-amine] in rodent models of movement disorders and depression J. Pharmacol. Exp. Ther. 2009, 330, 294-303
20. 2A adenosine antagonists J. Med. Chem. 1996, 39, 1164-1171
21. 2A receptor antagonists: arylpiperazine derivatives of pyrazolo[4,3- e ]-1,2,4-triazolo[1,5- c ] Bioorg. Med. Chem. Lett. 2007, 17, 1376-1380
22. 8 pyrazole nitrogen J. Med. Chem. 2000, 43, 4768-4780
23. 3 adenosine receptor antagonists J. Med. Chem. 2002, 45, 770-780
24. 3 adenosine receptor antagonist J. Med. Chem. 2002, 45, 3579-3582
25. 3 adenosine receptor antagonists. Influence of the heteroaryl substituent on binding affinity and molecular modeling investigation J. Med. Chem. 2006, 49, 1720-1729
26. 3 adenosine receptor antagonists: new insight into structure activity relationship and receptor antagonist recognition J. Med. Chem. 2010, 53, 3361-3375
27. 2A receptor antagonists Bioorg. Med. Chem. Lett. 2004, 14, 4835-4838
28. 2A receptor antagonists J. Med. Chem. 2004, 47, 6218-6229
29. 2A receptor antagonists J. Med. Chem. 2005, 48, 2009-2018
30. 2A selective adenosine receptor antagonist Br. J. Pharmacol. 1995, 115, 1096-1102
31. 2B receptor. Derivatives of the triazolotriazine adenosine receptor antagonist ZM241385 with high affinity Drug Dev. Res. 1999, 48, 95-103
32. 2B adenosine receptors Drug Des. Discovery 1999, 16, 217-226
33. 2B adenosine receptor subtypes: a molecular modeling investigation J. Med. Chem. 2003, 46, 4287-4296
34. Pastorin, G.; Federico, S.; Paoletta, S.; Corradino, M.; Cateni, F.; Cacciari, B.; Klotz, K. N.; Gao, Z. G.; Jacobson, K. A.; Spalluto, G.; Moro, S. Synthesis and pharmacological characterization of a new series of 5,7-disubstituted [1,2,4]triazolo[1,5- a ][1,3,5]triazine derivatives as adenosine receptor antagonists: a preliminary inspection of ligand-receptor recognition process Bioorg. Med. Chem. 2010, 18, 2524-2536
35. Peters, E.; Holland, J. F.; Bryant, B.; Minnemeyer, H. J.; Hohenstein, C.; Tieckelmann, H. Synthesis and tumor-inhibitory properties of 2-methylthio-4-(substituted-anilino)-5-carbethoxypyrimidines Cancer Res. 1959, 19, 729-737
36. Tsumoki, H.; Shimada, J.; Imma, H.; Nakamura, A.; Nonaka, H.; Shiozaki, S.; Ichiwara, S.; Kanda, T.; Kuwana, Y.; Ichimura, M.; Suzuki, F. [1,2,4]Triazolo[1,5- c ]pyrimidine derivatives. Patent No. WO98/42711, EP0976753A1, January 2, 2004.
37. Klotz, K. N.; Hessling, J.; Hegler, J.; Owman, C.; Kull, B.; Fredholm, B. B.; Lohse, M. J. Comparative pharmacology of human adenosine receptor subtypes-Characterization of stably transfected receptors in CHO cells Naunyn-Schmiedeberg's Arch. Pharmacol. 1998, 357, 1-9
38. 3 adenosine receptors antagonists J. Med. Chem. 2012, 55, 9654-9668
39. De Lean, A.; Hancock, A. A.; Lefkowitz, R. J. Validation and statistical analysis of a computer modeling method for quantitative analysis of radioligand binding data for mixtures of pharmacological receptor subtypes Mol. Pharmacol. 1982, 21, 5-16
40. 1 -adenosine receptors J. Biol. Chem. 1985, 260, 14659-14664
41. Cheng, Y. C.; Prusoff, H. R. Relationships between the inhibition constant (Ki) and the concentration of inhibitor which causes 50% inhibition (IC50) of an enzymatic reaction Biochem. Pharmacol. 1973, 22, 3099-3108
42. Molecular Operating Environment (MOE), 2013.08; Chemical Computing Group, Inc., 1010 Sherbooke St. West, Suite #910, Montreal, QC, Canada, H3A 2R7, 2012.
43. Stewart, J. J. P.. MOPAC 7; Fujitsu Limited: Tokyo, Japan, 1993.
44. GOLD suite, version 5.1; Cambridge Crystallographic Data Centre: Cambridge, U. K.
45. Liu Liu, W.; Chun, E.; Thompson, A. A.; Chubukov, P.; Xu, F.; Katritch, V.; Han, G. W.; Heitman, L. H.; Ijzerman, A. P.; Cherezov, V.; Stevens, R. C. Structural basis for allosteric regulation of GPCRs by sodium ions Science 2012, 337, 232-236
46. Floris, M.; Sabbadin, D.; Medda, R.; Bulfone, A.; Moro, S. Adenosiland: Walking through adenosine receptors landscape Eur. J. Med. Chem. 2012, 58, 248-257
47. Ballesteros, J. A.; Weinstein, H. Integrated methods for the construction of three dimensional models and computational probing of structure-function relationships in G-protein coupled receptors Methods Neurosci. 1995, 25, 366-428
48. 2A receptor as a case study J. Chem. Inf. Model 2014, 10.1021/ci5002857