Structure-activity relationships and molecular modeling of 3,5-diacyl- 2,4-dialkylpyridine derivatives as selective A3 adenosine receptor antagonists

Journal of Medicinal Chemistry

Volumn 41, Issue 17, 1998, Pages 3186-3201

  Li, An Hu ^a   Moro, Stefano ^a   Melman, Neli ^a   Ji, Xiao Duo ^a   Jacobson, Kenneth A ^a  

^a NATIONAL INSTITUTES OF HEALTH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 PROPYL 2,4 DIETHYL 3 (ETHYLSULFANYLCARBONYL) 6 PHENYLPYRIDINE 5 CARBOXYLATE; 5 ETHYL 2,4 DIETHYL 3 (ETHYLSULFANYLCARBONYL) 6 PHENYLPYRIDINE 5 CARBOXYLATE; ADENOSINE A3 RECEPTOR ANTAGONIST; ADENOSINE RECEPTOR BLOCKING AGENT; UNCLASSIFIED DRUG;

ARTICLE; DRUG ACTIVITY; DRUG RECEPTOR BINDING; DRUG SELECTIVITY; DRUG STRUCTURE; DRUG SYNTHESIS; HYDROPHOBICITY; MOLECULAR MODEL; RECEPTOR AFFINITY; STRUCTURE ACTIVITY RELATION;

ADENOSINE; ANIMALS; BINDING, COMPETITIVE; BRAIN; DIHYDROPYRIDINES; DRUG DESIGN; HUMANS; IODINE RADIOISOTOPES; KINETICS; MODELS, MOLECULAR; MOLECULAR CONFORMATION; MOLECULAR STRUCTURE; PYRIDINES; RADIOLIGAND ASSAY; RATS; RECEPTOR, ADENOSINE A2A; RECEPTOR, ADENOSINE A3; RECEPTORS, PURINERGIC P1; RECOMBINANT PROTEINS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0032514382     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm980093j     Document Type: Article

References (42)

1. Jacobson, K. A.; van Rhee, A. M. In Purinergic Approaches in Experimental Therapeutics; Jacobson, K. A., Jarvis, M. F., Eds.; Wiley: New York, 1997; Development of selective purinoceptor agonists and antagonists, Chapter 6, pp 101-128.
2. 3 adenosine receptor is the unique adenosine receptor which facilitates release of allergic mediators in mast cells. J. Biol. Chem. 1993, 268, 16887-16890.
3. 2+-ionophore-induced secretion in a rat mast-cell line. J. Pharmacol. Exp. Ther. 1996, 276, 837-845.
4. 3 adenosine receptors: Novel ligands and paradoxical effects. Trends Pharmacol. Sci. 1998, 19, 184-191.
5. 3 receptor stimulation and cerebral ischemia. Eur. J. Pharmacol. 1994, 263, 59-67.
6. 3 receptor antagonists and protection cerebral ischemic damage in gerbils. Soc. Neurosci. 1997, Abstr. 745.16, 23, 1924.
7. 3 receptors in mast-cells. Trends Pharmacol. Sci. 1994, 15, 13-14.
8. 3 receptor stimulation inhibits migration of human eosinophils. J. Leukoc. Biol. 1997, 62, 465-468.
9. 3 adenosine receptor. Proc. Natl. Acad. Sci. U.S.A. 1992, 89, 7432-7436.
10. 3 adenosine receptor. Proc. Natl. Acad. Sci. U.S.A 1993, 90, 10365-10369.
11. 3 receptors. J. Med. Chem. 1996, 39, 2980-2989.
12. 3 adenosine receptor antagonists. J. Med. Chem. 1996, 39, 4667-4675.
13. 3 adenosine receptor antagonists. J. Med. Chem. 1997, 40, 2596-2608.
14. 3 receptor subtype. J. Med. Chem. 1996, 39, 4142-4148.
15. Karton, Y.; Jiang, J. L.; Ji, X. D.; Melman, N.; Olah, M. E.; Stiles, G. L.; Jacobson, K. A. Synthesis and biological-activities of flavonoid derivatives as as adenosine receptor antagonists. J. Med. Chem. 1996, 39, 2293-2301.
16. 3 adenosine receptor antagonists. Drug Dev. Res. 1996, 37, 131.
17. 3-adenosine receptors. J. Med. Chem. 1994, 37, 636-646.
18. 3 receptors. J. Clin. Invest. 1996, 98, 1773-1779.
19. 1 receptor mediated responses in rat hippocampus. J. Neurosci. 1997, 17, 607-614.
20. Macek, T. A.; Conn, P. J. PKC Inhibition of Group II mGlu Autoreceptor Function at Medial and Lateral Performant Path Synapses. Soc. Neurosci. 1997, 23, Abstr. 685.17, 1754.
21. Jacobson, K. A. Molecular probes for adenosine receptors. In Purines in Cellular Signalling: Targets for New Drugs; Jacobson, K. A., Daly, J. W., Manganiello, V., Eds.; Springer: New York, 1990; pp 54-64.
22. Chang, L.; et al. Bioconjugate Chem. 1998, submitted.
23. Rathke, M. W.; Deitch, J. the reaction of lithium ester enolates with acid chlorides. A convenient procedure for the preparation of β-keto esters. Tetrahedron Lett. 1971, 31, 2953-2956.
24. Nakabeppu, H.; Asada, M.; Oda, T.; Shinozaki, Y.; Yajima, T. Plasma and urinary metabolites of efonidipine hydrochloride in man. Xenobiotica 1996, 26, 229-239.
25. Kearsley, S. K.; Smith, G. M. an Alternative Method for the Alignment of Molecular Structures: Maximizing Electrostatic and Steric Overlap. Tetrahedron Comput. Methodol. 1990, 3, 615-633.
26. The program SYBYL 6.3 is available from TRIPOS Associates, St. Louis, MO, 1993.
27. MOPAC 6.0 available from Quantum Chemistry Program Exchange.
28. Dewar, M. J. S. E.; Zoebisch, G.; Healy, E. F. AM1: A New General Purpose Quantum Mechanical Molecular Model. J. Am. Chem. Soc. 1985, 107, 3902-3909.
29. Dobbs, K. D.; Hehre, W. J. Molecular orbital theory of the properties of inorganic and organometallic compounds 5. Extended basis sets for first-row transition metals. J. Comput. Chem. 1987, 8, 861-879.
30. Gaussian 94, Revision C.2; Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Gill, P. M. W.; Johnson, B. G.; Robb, M. A.; Cheeseman, J. R.; Keith, T.; Petersson, G. A.; Montgomery, J. A.; Raghavachari, K.; Al-Laham, M. A.; Zakrzewski, V. G.; Ortiz, J. V.; Foresman, J. B.; Cioslowski, J.; Stefanov, B. B.; Nanayakkara, A.; Challacombe, M.; Peng, C. Y.; Ayala, P. Y.; Chen, W.; Wong, M. W.; Andres, J. L.; Replogle, E. S.; Gomperts, R.; Martin, R. L.; Fox, D. J.; Binkley, J. S.; Defrees, D.; Baker, J. J.; Stewart, J. P.; Head-Gordon, M.; Gonzalez, C.; Pople, J. A. Gaussian, Inc., Pittsburgh, 1995.
31. Chirlian, L. E.; Francl, M. M. Atomic Charges Derived from Electrostatic Potentials: a Detailed Study. J. Comput. Chem. 1987, 8, 894-905.
32. The program PowerFit v.1.0 is available from MicroSimulations, 478 Green Mountain Road, Mahwah, NJ 07430, 1996.
33. Ghose, A. K.; Crippen, M. Atomic Physicochemical Parameters for three-Dimensional Structure-Directed Quantitative Structure-Activity Relationships I. Partition Coefficients as a Measure of Hydrophobicity. J. Comput. Chem. 1986, 7, 565-577.
34. The programs HyperChem release 4.5 and Chem Plus v.1.0 are avaiable from Hypercube Inc., 419 Phillip Street, Waterloo, Ontario N2L 3X2 Canada, 1995.
35. 6-phenylisopropyladenosine. Naunyn-Schmiedeberg's Arch. Pharmacol. 1980, 373, 179-187.
36. 2 receptors in rat brain tissue. J. Pharmacol. Exp. Ther. 1989, 251, 888-893.
37. 3 adenosine receptor. Mol. Pharmacol. 1994, 45, 978-982.
38. 50) of an enzyme reaction. Biochem. Pharmacol. 1973, 22, 3099-3108.
39. 3 adenosine receptor-selective antagonists. Neuropharmacology 1997, 36, 1157-1165.
40. - = thiolate). J. Med. Chem. 1996, 39, 1253-1261.
41. Witzemann, E. J.; Evans, W. L.; Hass, H.; Schroeder, E. F. dl-Glyceraldehyde diethyl acetal. Organic Syntheses; Wiley: New York, 1943; Collect. Vol. II, pp 307-308.
42. Oikawa, Y.; Sugano, K.; Yonemitsu, O. Meldrum's acid in Organic Synthesis. 2. General and Versatile Synthesis of β-Keto Esters. J. Org. Chem. 1978, 43, 2087-2088.