논문 초록

Isoxazoline, Isoxazole, and Oxadiazole Derivatives as M1 Muscarinic Acetylcholine Receptor Agonists
Insertion of a methylene linker between the 2-pyrrolidinone substituent and the isoxazoline core of the lead compound 1 previously reported resulted in the loss of its agonistic activity. One exception was the compound 6f having oxadiazole core and 2-azabicyclo[2.2.1]heptane substituent. Of the two isomers of 6f, exo-isomer (EC50 0.013 μM) was five- to six-fold more effective than endo-isomer (EC50 0.30 μM), and ca. two-fold active than the mother compound 1 (EC50 0.031 μM) in stimulating the M1 mAChR. Both isomers were moderately selective agonists for M1 mAChR over the rest four subtypes, and it could be explained by docking study on active conformation allosteric binding sites of M1–M5 mAChRs and calculating their binding energies.
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