10.1021/jm00097a008
The study investigates the synthesis and biological activity of a series of 3-isoxazolol amino acids, specifically focusing on compounds structurally related to homoibotenic acid. The researchers synthesized several analogues, including 4-butylhomoibotenic acid (4c), 4-octylhomoibotenic acid (4d), and 4-(2-hydroxyethyl)homoibotenic acid (4e), to explore their interactions with excitatory amino acid receptors, particularly the AMPA subtype. The study also attempted the synthesis of 4-(bromomethyl)homoibotenic acid (4f) but was unsuccessful. The synthesized compounds were evaluated for their receptor binding affinities and excitatory activities in a rat cortical slice preparation. Key findings include the equipotency of 4c and 4e as inhibitors of [3H]AMPA binding and their similar excitatory activities, while 4d exhibited weak NMDA receptor antagonism and high selectivity for calcium chloride-dependent [3H]glutamic acid binding. These results provide insights into the structure-activity relationships of these compounds and their potential as tools for studying the physiological relevance and pharmacological importance of excitatory amino acid receptors.
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