Synthesis of 1-methyl-5-(pyrazol-3- and -5-yl- and 1, 2, 4-triazol-3- and 5-yl)-1, 2, 3, 6-tetrahydropyridine derivatives and their evaluation as muscarinic receptor ligands.
A series of 1-methyl-5-(pyrazol-3- and -5-yl- and 1, 2, 4-triazol-3- and 5-yl)-1, 2, 3, 6-tetrahydropyridine derivatives structurally related to arecoline were synthesized and evaluated on M(1), M(2), and M(3) muscarinic receptors using [(3)H] pirenzepine and [(3)H] NMS as ligands. The binding affinity depended on the position and size of the substituents. The most interesting compounds were further evaluated in functional studies on isolated organs and in vivo for cholinergic side effects. Compounds 5 l and 6 i good M(1) and M(3) antagonistic properties in vitro and were devoid of cholinergic side effects in vivo.
Del Giudice
Maria Rosaria
MR
Laboratorio di Chimica del Far maco, Istituto Superiore di Sanità, Rome, Italy. mr.delgiudice@iss.it
Mustazza
Carlo
C
Borioni
Anna
A
Gatta
Franco
F
Tayebati
Khosrow
K
Amenta
Francesco
F
Tucci
Paolo
P
Pieretti
Stefano
S
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001667:Binding, Competitive; D018678:Cholinergic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008024:Ligands; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009928:Organ Specificity; D010095:Oxotremorine / Q000494:pharmacology; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011817:Rabbits; D011976:Receptors, Muscarinic / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013552:Swine; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects; D014649:Vas Deferens / Q000187:drug effects
D018678:Cholinergic Agents; D008024:Ligands; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D011720:Pyrazoles; D011725:Pyridines; D011976:Receptors, Muscarinic; D014230:Triazoles; D010095:Oxotremorine; D001285:Atropine