Takahashi_1982_J.Med.Chem_25_919

Reference

Title : (+\/-)-2-Depentylperhydrohistrionicotoxin: a new probe for a regulatory site on the nicotinic acetylcholine receptor-channel - Takahashi_1982_J.Med.Chem_25_919
Author(s) : Takahashi K , Jacobson AE , Mak CP , Witkop B , Brossi A , Albuquerque EX , Warnick JE , Maleque MA , Bavoso A , Silverton JV
Ref : Journal of Medicinal Chemistry , 25 :919 , 1982
Abstract :

(+/-)-2-Depentylperhydrohistrionicotoxin (4), several of its analogues, and N- and O-substituted derivatives were prepared and tested for their effects on the neuromuscular transmission of the frog sartorius muscle. Compound 4, its N-methyl derivative 5, the O-acetyl derivative 9, and the quaternary methiodides 19 and 20 blocked the indirectly elicited twitch. The oxidation of 4 and 5 to ketones 12 and 14 and their reduction to the epimeric alcohols 17 and 18 afforded materials with substantially reduced activity. N-Acetylation of 4 to 11 changed the course of the activity to a transient potentiation of muscle twitch. Both 4 and 5 were not very toxic to mice after subcutaneous administration. (+/-)-7-n-Butyl-1-azaspiro[5,5]undecan-8-one (12) epimerized readily at room temperature to afford the epimer 13, and preparation of the hydrochloride of its N-methylated derivative 14 was accompanied by a retro-Michael reaction, affording the 2-n-butyl-3-[4-(methylamino)butyl]cyclohexene-2-one (22). The strongly hydrogen-bonded alcohol 4 was analyzed as the hydrobromide by a single-crystal X-ray analysis, confirming its structure.

PubMedSearch : Takahashi_1982_J.Med.Chem_25_919
PubMedID: 6288946

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Citations formats

Takahashi K, Jacobson AE, Mak CP, Witkop B, Brossi A, Albuquerque EX, Warnick JE, Maleque MA, Bavoso A, Silverton JV (1982)
(+\/-)-2-Depentylperhydrohistrionicotoxin: a new probe for a regulatory site on the nicotinic acetylcholine receptor-channel
Journal of Medicinal Chemistry 25 :919

Takahashi K, Jacobson AE, Mak CP, Witkop B, Brossi A, Albuquerque EX, Warnick JE, Maleque MA, Bavoso A, Silverton JV (1982)
Journal of Medicinal Chemistry 25 :919