Adenosine A 2A receptor agonists: CoMFA-based selection of the most predictive conformation

SAR and QSAR in Environmental Research

Volumn 13, Issue 2, 2002, Pages 227-235

  Doytchinova, I ^a   Valkova, I ^a   Natcheva, R ^a  

^a MEDICAL UNIVERSITY OF SOFIA   (Bulgaria)

Author keywords

2 Alkyloxy , 2 aryloxy And 2 aralkyloxy adenosines; 3d QSAR; Adenosine A 2A Receptor Agonists; Comfa; Most Predictive Conformation

Indexed keywords

ALKYNES; CONFORMATIONS;

2-ALKYLOXY-, 2-ARYLOXY- AND 2-ARALKYLOXY-ADENOSINE; 3D-QSAR; ADENOSINE A 2A RECEPTOR AGONIST; ADENOSINE RECEPTOR; ARYLOXY; COMFUM; COMPARATIVE MOLECULAR FIELD ANALYSIS; MOST PREDICTIVE CONFORMATION; PREDICTIVE POWER; PREDICTIVITY;

ADENOSINE; ADENOSINE A2A RECEPTOR; ADENOSINE RECEPTOR; LIGAND;

ARTICLE; CHEMICAL MODEL; CHEMISTRY; CONFORMATION; DRUG POTENTIATION; FORECASTING; HUMAN; PHYSIOLOGY; SOLUBILITY;

ADENOSINE; FORECASTING; HUMANS; LIGANDS; MODELS, CHEMICAL; MOLECULAR CONFORMATION; RECEPTOR, ADENOSINE A2A; RECEPTORS, PURINERGIC P1; SOLUBILITY;

EID: 0036490889     PISSN: 1062936X     EISSN: 1029046X     Source Type: Journal    
DOI: 10.1080/10629360290002712     Document Type: Article

References (17)

1. Collis, M.G., and Hourani, S.M.O., 1993. “Adenosine receptor subtypes”. Trends Pharmacol. Sci., 14: 360–366.
2. Linden, J., 1994. “Cloned adenosine A 3 receptors: Pharmacological properties, species differences and receptor functions”. Trends Pharmacol. Sci., 15: 298–306.
3. Müller, C.E., and Scior, T., 1993. “Adenosine receptors and their modulators”. Pharm. Acta Helv., 68: 77–111.
4. IJzerman, A.P., van der Wenden, E.M., van Galen, P.J.M., and Jacobson, K.A., 1994. “Molecular modelling of adenosine receptors. The ligand binding site on the rat adenosine A 2a receptor”. Eur. J. Pharmacol., 268: 95–104.
5. Ijzerman, A.P., van Galen, P.J.M., and Jacobson, K.A., 1992. “Molecular modelling of adenosine receptors. I. The ligand binding site on the A 1 receptor”. Drug Des. Discov., 9: 49–67.
6. Mager, P.P., Richter, M., and Reinhardt, R., 1995. “Molecular simulation applied to 2-(N′-alkylidenhydrazino)- and 2-(N′-aralkylidenhydrazino)adenosine A 2 agonists”. Eur. J. Med. Chem., 30: 15–25.
7. Kim, J., Wess, J., van Rhee, A.M., Schoneberg, T., and Jacobson, K.A., 1995. “Site-directed mutagenesis identifies residues involved in ligand recognition in the human A 2a adenosine receptor”. J. Biol. Chem., 270: 13987–13997.
8. Cramer, R.D, III, Patterson, D.E., and Bunce, J.D., 1988. “Comparative molecular field analysis (CoMFA). 1.Effect of shape on binding of steroids to carrier proteins”. J. Am. Chem. Soc., 110: 5959–5967.
9. Daly, J.W., Padgett, W.L., Secunda, S.I., Thompson, R.D., and Olsson, R.A., 1993. “Structure-activity relationships for 2-substituted adenosines at A 1 and A 2 adenosine receptors”. Pharmacology, 46: 91–100.
10. Matova, M., Nacheva, R., and Boicheva, S., 1997. “QSAR analisis of 2-alkyloxy and 2-aralkyloxy adenosine A 1 - and A 2 -agonists”. Eur. J. Med. Chem., 32: 505–513.
11. Chem-X ® July 1999. Chemical Design Ltd., Roundway House, Cromwell Park, Chipping Norton, Oxfordshire OX7 5SR, UK.
12. Allen, F.H., Bellard, S., Brice, M.D., Cartwright, B.A., Doubleday, A., Higgs, H., Hummelink, T., Hummelink-Peters, B.G., Kennard, O., Montherwell, W.D.S., Rodgers, J.R., and Watson, D.G., 1979. “The Cambridge crystallographic data centre: computer-based search, retrieval, analysis and display of information”. Acta Crystallogr., B35: 2331–2339.
13. Burkert, U., and Allinger, N.L., 1982. Molecular Mechanics, 339Washington, DC: American Chemical Society.
14. Dewar, M.J.S., Zoebisch, E.G., Healy, E.F., and Stewart, J.J.P., 1985. “AM1: a new general purpose quantum mechanical molecular model”. J. Am. Chem. Soc., 107: 3902–3909.
15. Dunn, W.J., III, Wold, S., Edlund, U., Hellberg, S., and Gasteiger, J., 1984. “Multivariate structure-activity relationship between date from a battery of biological tests and an ensemble of chemical descriptors: the PLS method”. Quant. Struct.-Act. Relat., 3: 131–137.
16. Cristalli, G., Eleuteri, A., Vittori, S., Volpini, R., Lohse, M.J., and Klotz, K.-N., 1992. “2-Alkynyl derivatives of adenosine and adenosine-5′-N-ethyluronamide as selective agonists at A 2 adenosine receptors”. J. Med. Chem., 35: 2363–2368.
17. Cristalli, G., Volpini, R., Vittori, S., Camaioni, E., Monopoli, A., Conti, A., Dionisotti, S., Zocchi, C., and Ongini, E., 1994. “2-Alkynyl derivatives of adenosine-5′-N-ethyluronamide: selective A2 adenosine receptor agonists with potent inhibitory activity on platelet aggregation”. J. Med. Chem., 37: 1720–1726.