Bicyclic dioxolanes as potential antimuscarinic agents.
A series of rigid compounds--derivatives of 2,2-diphenyl-[1,3]-dioxolan-4-ylmethyl-dimethylamine methiodide (1b)--has been synthesized and tested to evaluate affinity and selectivity for M1, M2, and M3 muscarinic receptors. The stereochemistry of the annulation does not influence the activity; the optimal distance between nitrogen and the benzhydryl group seems to be that with the nitrogen in the rigid ring (2b) or the nitrogen directly bound at the cyclopentane nucleus (9b, 11b). The different structure-activity relationships between tertiary amines (a series) and the corresponding quartnerary salts (b series) suggest a different binding to the receptor sites.
Piergentili
A
A
Dipartimento di Scienze Chimiche, Università di Camerino, Italy.
Angeli
P
P
Giannella
M
M
Pigini
M
M
Quaglia
W
W
Tayebati
S K
SK
D000818:Animals; D004148:Dioxolanes / Q000138:chemical synthesis* / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008968:Molecular Conformation; D018727:Muscarinic Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D011817:Rabbits; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D004148:Dioxolanes; D018727:Muscarinic Antagonists