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Die Position 5 im Oxotremorin‐Gerüst: Eine zentrale Stelle für die Steuerung der Aktivität am muscarinischen Rezeptor
Author(s) -
Amstutz René,
Closse Annemarie,
Gmelin Gernot
Publication year - 1987
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19870700827
Subject(s) - chemistry , oxotremorine , muscarinic acetylcholine receptor , pirenzepine , muscarine , stereochemistry , receptor , biochemistry
Position 5 at the Oxotremorine Skeleton as the Stearing Position for Activity at the Muscarinic Receptors Substitution of the Ch 2 group at position 5 of oxotremorine ( 2 ) by electronegative atoms like O‐ or N‐atom, or by sterically bulkier groups like methyl, N ‐formyl, or N ‐acetyl Changes the pharmacological profile of oxotremorine drastically. The O‐ and N‐analogues were potent but unselective (M 1 /M 2 ) muscarinic agonists. The methyl analogue ((R)‐BOK‐1) is a muscarine antagonist which is 10 times more potent on the ganglion cervical superius (pA 2 = 9.3) than pirenzepine and is able to distinguish between the ileal and ganglion receptor by a factor of 100. The N ‐formyl derivative differentiates between the two receptors by a factor of 500 with a potency comparable to pirenzepine. The two M 1 ‐selective antagonists have higher affinity to the rat‐ganglion receptors compared to the affinity to rat‐cortex homogenate. The synthesis and the pharmacological activity of several new oxotremorine analogues are discussed.