| Autor: |
Orlek BS; SmithKline Beecham Pharmaceuticals, Medicinal Research Centre, Harlow, Essex, England., Blaney FE, Brown F, Clark MS, Hadley MS, Hatcher J, Riley GJ, Rosenberg HE, Wadsworth HJ, Wyman P |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of medicinal chemistry [J Med Chem] 1991 Sep; Vol. 34 (9), pp. 2726-35. |
| DOI: |
10.1021/jm00113a009 |
| Abstrakt: |
The link between the cognitive deficit associated with Alzheimer type dementia and the loss of cholinergic function in the disease provides a basis for examining muscarinic agonists as potential therapeutic agents. This paper describes the design and synthesis of novel azabicyclic methyl esters as ligands for the muscarinic receptor. Replacement of the methyl ester by a 3-methyl-1,2,4-oxadiazole ring produces potent metabolically more stable muscarinic agonists capable of penetrating the central nervous system. These compounds generally show improved affinity relative to the corresponding methyl esters. 3-Methyl-1,2,4-oxadiazole 7b has an affinity 4 times that of acetylcholine. Receptor affinity is discussed in relation to the size and geometry of the azabicyclic ring and the electronic properties of the heteroaromatic ring. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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