Thienocycloheptapyridazines as new muscarinic agents.
A series of thienocycloheptapyridazines (3aa-dd), structurally related to Minaprine, was synthesized and compounds tested for their affinity towards muscarinic receptors. All of them showed Ki values in the micromolar range towards both the antagonist 3H-QNB and the agonist 3H-OXO-M, thus indicating that they act as antagonists at the muscarinic receptors. Moreover a theoretical study was performed on their interaction behaviour with a three dimensional (3-D) model of the human m1 muscarinic receptor.
Barlocco
D
D
Ist. Chimica Farmaceutica e Tossicologica, Milano, Italy.
Cignarella
G
G
Fanelli
F
F
Vitalis
B
B
Matyus
P
P
De Benedetti
P G
PG
D000818:Animals; D006801:Humans; D008297:Male; D018721:Muscarinic Agonists / Q000138:chemical synthesis* / Q000378:metabolism; D018727:Muscarinic Antagonists / Q000138:chemical synthesis* / Q000378:metabolism; D011724:Pyridazines / Q000138:chemical synthesis* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000378:metabolism; D013329:Structure-Activity Relationship
D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D011724:Pyridazines; D011976:Receptors, Muscarinic; C006149:minaprine