Synthesis of pyrazolone derivatives. XXXVI. Synthetic and pharmacological studies on (4S,7R)-4,7-methano-1H(or 2H)-indazoles and indazolium compounds.

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Abstract
(4S,7R)-1 and 2-substituted-4,7-methanoindazoles were synthesized. The nucleophilic reaction of substituted hydrazines with (1R,4S)-3-hydroxymethyleneborane-2-one (1) gave corresponding (4S,7R)-1-substituted-4,7-methano-1H-indazoles (3). Attempts to synthesize 2-substituted-4,7-methanoindazoles starting from (1R,4S)-3-acetoxymethylenebornane-2-one (5a) were unsuccessful. Quarternization of (4S,7R)-4,7-methanoindazole (3a) afforded (4S,7R)-4,7-methano-1H-indazolium compounds (8, 9 and 10a, b). (4S,7R)-2-substituted-4,7-methanoindazoles were successfully obtained by the reaction of 3a with acetic anhydride and hydroxylamine-O-sulfonic acid. The structure assignments of the 1 and 2-substituted compounds were made on the basis of their NMR spectra. Pharmacological profiles of newly synthesized compounds were studied in vivo and in vitro. The behavioral symptoms of mice treated with compounds 10a and 10b were serious abnormal gait and catalepsy. The in vitro studies on isolated ileum preparation and isolated heart preparation suggested that compound 10b has effective anticholinergic and antihistaminergic actions.

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