1. The absolute configuration plays an important role in muscarinic activity of BGT-A and its analogs.
- Author
-
Niu YY, Zhu L, Cui YY, Liu HZ, Chen HZ, and Lu Y
- Subjects
- Animals, Female, Guinea Pigs, Male, Motor Activity drug effects, Motor Activity physiology, Muscarinic Agonists chemical synthesis, Muscle, Skeletal chemistry, Rabbits, Rats, Receptors, Muscarinic drug effects, Receptors, Muscarinic metabolism, Stereoisomerism, Submandibular Gland metabolism, Tropanes chemistry, Tropanes metabolism, Muscarinic Agonists chemistry, Muscarinic Agonists pharmacology, Tropanes chemical synthesis
- Abstract
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. more...
- Published
- 2008
- Full Text
- View/download PDF