2-(Substituted)amino-2,8-diazaspiro[4,5] decan-1,3-diones as potential muscarinic agonists: Synthesis, modeling and binding studies

Drug Design and Discovery

Volumn 14, Issue 2, 1996, Pages 129-143

  Barlocco, Daniela ^a   Fanelli, Francesca ^a   Cignarella, Giorgio ^b   Villa, Stefania ^b   Cattabeni, Flaminio ^c   Balduini, Walter ^c   Cimino, Mauro ^c   De Benedetti, Piero G ^a  

^a UNIVERSITY OF MODENA AND REGGIO EMILIA   (Italy)

^b Istituto di Chimica Farmaceutica e Tossicologica   (Italy)

^c UNIVERSITY OF URBINO   (Italy)

Author keywords

2,8 disubstituted 2,8 diazaspiro 4,5 decan 1,3 diones; Molecular Dynamics; Muscarinic agonists; RS 86; Theoretical molecular descriptors

Indexed keywords

2 ETHYL 8 METHYL 2,8 DIAZASPIRO[4.5]DECANE 1,3 DIONE; CARBACHOL; MUSCARINIC AGENT; SPIRO COMPOUND; SPIRO[4.5]DECANE DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; BINDING AFFINITY; CONTROLLED STUDY; DRUG RECEPTOR BINDING; DRUG SYNTHESIS; MOLECULAR DYNAMICS; MOLECULAR MODEL; NONHUMAN;

ANIMALS; CARBACHOL; CEREBRAL CORTEX; COMPUTER SIMULATION; MODELS, MOLECULAR; MUSCARINIC AGONISTS; PROTEIN CONFORMATION; QUINUCLIDINYL BENZILATE; RATS; RECEPTORS, MUSCARINIC; SPIRO COMPOUNDS; SUCCINIMIDES;

EID: 0030447512     PISSN: 10559612     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (29)

1. Moos, W., Davis, R.E., Schwarz, R.D. and Gamzu, E.R. (1988) Cognition activators, Med Res. Rev., 8, 353-391.
2. John, V., Lieberburg, I. and Thorsett, E.D. (1993) Alzheimer's disease: current therapeutic approaches, Ann. Rep. Med. Chem., 28, 197-206.
3. Cignarella, G., Villa, S., Cattabeni, F., Reno', F., Cimino, M., De Benedetti, P.G. and Barlocco, D. (1994) Synthesis of a new series of 2,8-disubstituted-2,8-diazaspiro[4,5]decan-1-ones as potential muscarinic agonists, Eur. J. Med Chem., 29, 955-961.
4. Cignarella, G., Villa, S. and Barlocco, D. (1993) Synthesis of a new series of 8-substituted-2,8-diazaspiro[4,5]decan-3-ones, J. Heterocyclic Chem., 30, 1357-1359.
5. Cignarella, G., Villa, S. and Barlocco, D. (1993) Synthesis of a new series of N-substituted-3-[1-alkyl(aryl)4-piperidyl]azetidin-2-ones as possible muscarinic agents, J Heterocyclic Chem., 30, 1337-1339.
6. Cignarella, G., Villa, S. and Barlocco, D. (1993) Synthesis and pharmacological evaluation of a new class of 2-oxo-8-azaspiro[4,5]decan-1-ones as analogues of the muscarinic agonist RS-86, Il Farmaco, 48, 1439-1445.
7. Mouradian, M.M., Mohr, E., Williams, J A. and Chase, T.N. (1988) No response to high dose muscarinic agonist therapy in Alzheimer's disease, Neurology, 38, 606-608.
8. 1B-adrenergic and m3-muscarinic receptors. Protein Engineering, 8, 557-564.
9. Fanelli, F., Menziani, M.C. and De Benedetti, P.G. (1995) Molecular Dynamic simulations of m3-muscarinic receptor activation and QSAR analysis. Bioorg. & Med. Chem., 3, 1465-1477.
10. Zhu, S.Z., Wang, S.Z., Hu, J. and El-Fakahany, E. (1994) An arginine residue conserved in most G Protein-Coupled receptors is essential for the function of the m1-muscarinic receptor, Mol. Pharmacol., 45, 517-523.
11. Jones, P.O., Curtis, C.A.M. and Hulme, C. (1995) The function of a highly-conserved arginine residue in activation of the muscarinic M1 receptor, Eur. J. Pharmacol., 288, 251-257.
12. Wess, J. (1993) Mutational Analysis of muscarinic acetyacholine receptors: structural basis of ligand/ receptor/G protein interactions, Life Sci., 53, 1447-1463.
13. Fanelli, F., Menziani, M.C., Carotti, A. and De Benedetti. P.G. (1994) Theoretical Quantitative Structure-Activity Relationship Analysis on three dimensional models of ligand-m1 muscarinic receptor complexes, Bioorg. & Med. Chem., 2, 195-211.
14. Hibert, M., Hoflack. J., Trumpp-Kallmeyer S., Paquet, J-L., Leppik, R., Barberis, C., Mouillac B., Chini, B. and Jard S., (1995) 3D models of hormone receptors: experimental validation, Eur. J. Med. Chem., 30. 189s-199s.
15. Saunders, J., Cassidy, M., Freedman, S.B., Harley, E.A., Iversen, L.L., Kneen, C., MacLeod, A.M., Merchant, K.J., Snow, R.J. and Baker, R. (1990) Novel quinuclidine-based ligands for the muscarinic cholinergic receptor, J Med Chem, 33, 1128-1138.
16. Fanelli, F., Menziani, M.C., Carotti, A. and De Benedetti, P.G. (1993) Theoretical Quantitative Structure Activity Analysis of quinuclidine-based muscarinic cholinergic receptor ligands, J. Mol. Struct. (Theochem), 283, 63-71.
17. De Benedetti, P.G., Menziani, M C., Cocchi, M. and Fanelli, F. (1995) Prototropic molecular forms and theoretical descriptors in QSAR analysis, J. Mol Struct. (Theochem), 333, 1-17.
18. Yamamura, H.I. and Snyder, S.H (1974) Muscarinic cholinergic binding in rat brain, Proc. Natl. Acad. Sci USA, 71, 1725-1729.
19. Balduini, W., Murphy, D.S. and Costa, L.G. (1987) Developmental changes in muscarinic receptor-stimulated phosphoinositide metabolism in rat brain, J. Pharmacol Exp. Therap. 241, 421-427.
20. Costa, L.G., Kaylor, G. and Murphy, S.D (1986) Carbachol- and norepinephrine-stimulated phosphoinositide metabolism in rat brain: effect of chronic cholinesterase inhibition, J Pharmacol. Exp. Ther., 239, 32-37.
21. Glowinski, J. and Iversen, L.L (1966) Regional studies of catecholamines in the brain, J. Neurochem., 13, 655-662.
22. Fanelli, F., Menziani, M.C., Cocchi, M. and De Benedetti, P.G. (1995) Comparative molecular dynamics study of the seven-helix bundle arrangement of G-protein coupled receptors, J. Mol. Struct. (Theochem), 333, 49-69.
23. Baldwin, J.M. (1993) The probable arrangement of the helices in G protein- coupled receptors. EMBO J., 12, 1693-1703.
24. Schertler, G.F.X., Villa, C. and Henderson, R. (1993) Projection structure of rhodopsin, Nature, 362, 770-772.
25. Henderson, R., Baldwin, J.M. and Ceska, T.A. (1990) Model for the structure of bacteriorhodopsin based on high-resolution electron cryo-microscopy, J. Mol Biol., 213, 899-929.
26. QUANTA/CHARMm, 1990, Molecular Simulations, 200 Fifth Avenue, Waltham, MA 02254.
27. Brooks, B.R , Bruccoleri, R.E., Olafson, B.D., States, D.J., Swaminathan, S. and Karplus, M. (1983) CHARMM: a program for macromolecular energy minimization, and dynamics calculations, J. Comput. Chem., 4, 187-217.
28. van Gunsteren, W.F. and Berendsen, J.C.(1987) Algorithms for macromolecular dynamics and constraint dynamics, Mol. Phys., 34, 1311.
29. Dewar, M.J.S., Zoebisch, E.G., Healey, E.F. and Stewart, J.J.P. (1985) AMI: a new general purpose quantum mechanical molecular model, J. Am. Chem. Soc., 107, 3902.