Synthesis and structure-activity relationship studies in a series of 2-substituted 1,3-dioxolanes modified at the cationic head.
To develop ligands that may be useful in exploring muscarinic receptor heterogeneity, we synthesized a series of analogues of 2,2-diphenyl-[1,3]-dioxolan-4-ylmethyl-dimethylamine oxalate and methiodide bearing a modified cationic head. These compounds, when tested on tissues containing the three subtypes M1, M2, and M3, behaved as muscarinic antagonists whose results showed that different substituents on the quaternary and tertiary nitrogen affect affinity and selectivity in different ways. In particular comparison of the affinities of these ligands with those of the reference compounds points out that compounds bearing an ethyl substituent improve the affinity of the molecule at the three subtypes while compounds bearing a phenethyl substituent are more selective for the M3 sites.
Angeli
P
P
Dipartimento di Scienze Chimiche, Università di Camerino, Italy.
Brasili
L
L
Cingolani
M L
ML
Marucci
G
G
Piergentili
A
A
Pigini
M
M
Quaglia
W
W
D000588:Amines / Q000138:chemical synthesis; D000818:Animals; D001667:Binding, Competitive; D002412:Cations; D004148:Dioxolanes / Q000737:chemistry* / Q000494:pharmacology; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D007454:Iodides / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D018727:Muscarinic Antagonists / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D009153:Mutagens / Q000737:chemistry* / Q000494:pharmacology; D010070:Oxalates / Q000737:chemistry; D011817:Rabbits; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014018:Tissue Distribution; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism; D014649:Vas Deferens / Q000187:drug effects / Q000378:metabolism
D000588:Amines; D002412:Cations; D004148:Dioxolanes; D007454:Iodides; D018727:Muscarinic Antagonists; D009153:Mutagens; D010070:Oxalates; D011976:Receptors, Muscarinic; C010962:formal glycol