Synthesis of spiro[isobenzofuran-1(3H),4'-piperidines] as potential central nervous system agents. 2. Compounds containing a heteroatom attached to nitrogen.
The synthesis and antitetrabenazine activity of a series of N-heteroatom derivatives of 3-phenylspiro[isobenzofuran-1,4'-piperidines] are reported. Optimal antitetrabenazine activity is associated with compounds containing a sterically unhindered, basic nitrogen. Hydroxylamines 6, 11, 12, and 13 possess the most significant activity with ED50's of 1.4, 3.5, 4.7, and 4.0, respectively.
D000818:Animals; D000928:Antidepressive Agents / Q000138:chemical synthesis* / Q000627:therapeutic use; D001572:Benzofurans / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D001763:Blepharoptosis / Q000139:chemically induced / Q000188:drug therapy; D008722:Methods; D051379:Mice; D010880:Piperidines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D013329:Structure-Activity Relationship; D013747:Tetrabenazine / Q000037:antagonists & inhibitors / Q000494:pharmacology
D000928:Antidepressive Agents; D001572:Benzofurans; D010880:Piperidines; D013747:Tetrabenazine