Both enantiomers of 2, 3, and 4, three bioactive analogs of muscarinic agonist BGT-A were prepared respectively and underwent functional studies and radioreceptor binding assays. 6S enantiomers of 2, 3, and 4 showed obvious muscarinic activity, while 6R ones elicited little muscarinic activity by functional studies. Besides, the affinity of 6S enantiomers of 2, 3, and 4 was greatly larger than that of their 6R enantiomers respectively. All these pharmacological results indicated the 6S configuration was beneficial for the active BGT-A analogs to bind with the muscarinic receptors. The finding was in good agreement with our previous SAR study to BGT-A and its active analogs by computational approach. The understanding to the relationship between muscarinic activity and absolute configuration will provide the basis for successive screening of BGT-A analogs as effective muscarinic agonists or antagonists in clinical use.
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