title: 2-(Substituted)amino-2,8-diazaspiro[4,5]decan-1,3-diones as potential muscarinic agonists: synthesis, modeling and binding studies.
abstract: A series of 2-(acyl)amino-8-substituted-2,8-diazaspiro[4,5]decan-1,3-diones (5a-j), structurally related to the muscarinic agonist RS-86, was synthesized and compounds tested for their affinity towards muscarinic receptors. Though all compounds proved to be less active than the model in binding studies, only three derivatives (5a, b, c) being able to significantly displace 3H-QNB at mM concentration, their behaviour could be interpreted in terms of theoretical molecular descriptors computed on the basis of the suggestions coming from Molecular Dynamics simulations of ligand-receptor complexes.
authors.forename: D
authors.initials: D
authors.lastname: Barlocco
authors.forename: F
authors.initials: F
authors.lastname: Fanelli
authors.forename: G
authors.initials: G
authors.lastname: Cignarella
authors.forename: S
authors.initials: S
authors.lastname: Villa
authors.forename: F
authors.initials: F
authors.lastname: Cattabeni
authors.forename: W
authors.initials: W
authors.lastname: Balduini
authors.forename: M
authors.initials: M
authors.lastname: Cimino
authors.forename: P G
authors.initials: PG
authors.lastname: De Benedetti
mesh_terms: D000818:Animals; D002217:Carbachol / Q000737:chemistry; D002540:Cerebral Cortex / Q000378:metabolism; D003198:Computer Simulation; D008958:Models, Molecular; D018721:Muscarinic Agonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011487:Protein Conformation; D011813:Quinuclidinyl Benzilate / Q000494:pharmacology; D051381:Rats; D011976:Receptors, Muscarinic / Q000737:chemistry / Q000187:drug effects; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013388:Succinimides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D018721:Muscarinic Agonists; D011976:Receptors, Muscarinic; D013141:Spiro Compounds; D013388:Succinimides; D011813:Quinuclidinyl Benzilate; D002217:Carbachol