Synthesis of spiro[tetralin-2,2'-pyrrolidine] and spiro[indan-2,2'-pyrrolidine] derivatives as potential analgesics.
Spiro[tetralin-2,2'-pyrrolidine] (13) and spiro[6-methoxytetralin-2,2'-pyrrolidine] (17) were prepared by initial Michael condensation of 2-nitrotetralin and 6-methoxy-2-nitrotetralin, respectively, with methyl acrylate to give 7 and 8, both of which could be reductively cyclized to 10 and 11, followed by LiAlH4 reduction. Spiro[indan-2,2'-pyrrolidine] (15) was prepared in an analogous manner form 2-nitroindan, and spiro[6-hydroxytetralin-2,2'-pyrrolidine] (19) was prepared by O-demethylation of 17. Compound 13 and its N-methyl derivative, 14, both showed good analgesic activity. Compounds 13-16 all possessed weak antidepressant properties, but neither 19 nor its N-methyl derivative 20 had any significant CNS activity.
D000085:Acetates / Q000037:antagonists & inhibitors; D000700:Analgesics / Q000138:chemical synthesis*; D000818:Animals; D000928:Antidepressive Agents / Q000138:chemical synthesis; D007035:Hypothermia / Q000139:chemically induced / Q000517:prevention & control; D007189:Indans / Q000138:chemical synthesis* / Q000494:pharmacology; D007192:Indenes / Q000138:chemical synthesis*; D051379:Mice; D009281:Naphthalenes / Q000138:chemical synthesis*; D011759:Pyrrolidines / Q000138:chemical synthesis / Q000494:pharmacology; D012110:Reserpine / Q000037:antagonists & inhibitors; D013035:Spasm / Q000139:chemically induced / Q000517:prevention & control; D013141:Spiro Compounds / Q000138:chemical synthesis / Q000494:pharmacology; D013764:Tetrahydronaphthalenes / Q000138:chemical synthesis* / Q000494:pharmacology
D000085:Acetates; D000700:Analgesics; D000928:Antidepressive Agents; D007189:Indans; D007192:Indenes; D009281:Naphthalenes; D011759:Pyrrolidines; D013141:Spiro Compounds; D013764:Tetrahydronaphthalenes; D012110:Reserpine