Quinuclidin-2-ene-based muscarinic antagonists.
A series of achiral 3-heteroaryl substituted quinuclidin-2-ene derivatives and related compounds have been synthesized by facile methods. The compounds were evaluated for muscarinic and antimuscarinic properties in receptor binding studies using (-)-[3H]-QNB as the radioligand and in a functional assay using isolated guinea pig urinary bladder. 3-(2-Benzofuranyl)-quinuclidin-2-ene (15) displayed the highest M1-receptor affinity in the present series (Ki = 9.6 nM).
Hacksell
U
U
Department of Organic Pharmaceutical Chemistry, Uppsala Biomedical Center, Uppsala University, Sweden.
Nilsson
B M
BM
Nordvall
G
G
Johansson
G
G
Sundquist
S
S
Nilvebrant
L
L
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D015394:Molecular Structure; D018727:Muscarinic Antagonists / Q000737:chemistry / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009206:Myocardium / Q000378:metabolism; D010306:Parotid Gland / Q000187:drug effects / Q000378:metabolism; D011812:Quinuclidines / Q000737:chemistry / Q000494:pharmacology*; D011869:Radioligand Assay; D011976:Receptors, Muscarinic / Q000378:metabolism*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D001743:Urinary Bladder / Q000187:drug effects* / Q000378:metabolism
D018727:Muscarinic Antagonists; D011812:Quinuclidines; D011976:Receptors, Muscarinic