A series of 1-substituted 2,3-polymethyleneindoles was prepared and examined for central nervous system activity. A number of these compounds wrere found to be active as antidepressants. The required 2,3-polymethyleneindoles were prepared by suitable modifications of the Fischer indole synthesis from arylhydrazines and alicyclic ketones. These were converted to N-substituted derivatives by various methods.

Anal. (C15H22C1N0) C, , N [sample dried at 120°(0.5 mm) prior to analysis]. pKa Measurement The p values were determined potentiometrically as described by Albert and Serjeant19 by titration of of the HC1 salts (0.25 mmol) in 50% EtOH-H20 (47.5 ml) against 0.05 N KOH at 25°.

A series of tetrahydropyrrolo[1,2-a]quinoxalines and tetrahydropyrrolo[1,2-a]pyrido[3,2-a]pyrazines were synthesized and tested for their ability to relax K+-depolarized aortic smooth muscle and antihypertensive activity. It was shown that compounds producing the most relaxation of aortic smooth muscle (5-[2,6-dimethoxyphenyl)methyl]-1,2,3,3a-tetrahydropyrrolo[1,2-a] quinoxalin-4(5H)-one and 5-[(2,6-dimethoxyphenyl)methyl]-5,6,6a,7,8,9-hexahydropyrrolo[1,2- a] pyrazine, 10 and 19, respectively) demonstrated the least hypotensive activity. Those compounds that were the most effective hypotensive agents (6a,7,8,9-tetrahydro-5-(phenylmethyl)pyrido[3,2-a]pyrrolo[1,2-a]++ +pyrazin- 6(5H)-one and 6a,7,8,9-tetrahydro-5-(4-pyridinylmethyl)pyrido[3,2-e]pyrrolo [1,2-a]pyrazin-6(5H)-one, 12 and 13, respectively) displayed little vascular smooth muscle relaxant activity.

A new synthesis for 1,4-diazabicyclo [4.4.0 Jdecane has been developed. The synthesis of a series of 1,4-diazabicyclo [4.3.01nonanes has been accomplished for the first time. The 1,8-diazabicyclo [4.3.0 Jnonane system has also been synthesized for the first time. A new method for the preparation of 2-aminomethylpiperidines is also reported.

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