Molecular modulation of muscarinic antagonists. Synthesis and affinity profile of 2,2-diphenyl-2-ethylthio-acetic acid esters designed to probe the binding site cavity.
The synthesis and preliminary pharmacological profile of a new series of muscarinic antagonists, derived from previously studied 2,2-diphenyl-2-ethylthio-acetic acid esters, are reported. The parent molecules were decorated with linkers of different length, carrying an amino group to catch a putative anionic function outside the recognition site of the receptor. It was hoped that the interception of this function would give molecules with higher potency and selectivity. The attempt has not been successful, but a new series of compounds with a peculiar pharmacological profile has been identified.
Scapecchi
Serena
S
Dipartimento di Scienze Farmaceutiche, Università di Firenze, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Florence, Italy. serena.scapecchi@unifi.it
Martini
Elisabetta
E
Bellucci
Cristina
C
Buccioni
Michela
M
Dei
Silvia
S
Guandalini
Luca
L
Manetti
Dina
D
Martelli
Cecilia
C
Marucci
Gabriella
G
Matucci
Rosanna
R
D019342:Acetic Acid / Q000138:chemical synthesis* / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites / Q000502:physiology; D016466:CHO Cells; D006224:Cricetinae; D015195:Drug Design; D004952:Esters; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008968:Molecular Conformation; D018727:Muscarinic Antagonists / Q000138:chemical synthesis* / Q000378:metabolism*; D011817:Rabbits
D004952:Esters; D018727:Muscarinic Antagonists; D019342:Acetic Acid