Pempidine is a ganglion-blocking drug, first reported in 1958 by two research groups working independently, and introduced as an oral treatment for hypertension. [1 ] [2 ]
Pharmacology [ edit ]
Reports on the "classical" pharmacology of pempidine have been published.
[3 ] The Spinks group, at [4 ] ICI, compared pempidine, its N-ethyl analogue, and mecamylamine in considerable detail, with additional data related to several structurally simpler compounds. [3 ]
Toxicology [ edit ]
50 for the HCl salt of pempidine in mice: 74 mg/kg (i.v.); 125 mg/kg (i.p.); 413 mg/kg (p.o.). [3 ]
Chemistry [ edit ]
Pempidine is an
aliphatic, sterically hindered, cyclic, tertiary amine, which is a weak base: in its protonated form it has a pK a of 11.25. [5 ]
Pempidine is a liquid, b.p. 187-188°; d = 0.858 g/cm
3. [3 ]
Two early syntheses of this compound are those of Leonard and Hauck,
and Hall. [6 ] These are very similar in principle: Leonard and Hauck reacted [5 ] phorone with ammonia, to produce 2,2,6,6-tetramethyl-4-piperidone, which was then reduced by means of the [7 ] Wolff-Kishner reaction to 2,2,6,6-tetramethylpiperidine; this secondary amine was then N-methylated using methyl iodide and potassium carbonate. [8 ]
Hall's method involved reacting
acetone with ammonia in the presence of calcium chloride to give 2,2,6,6-tetramethyl-4-piperidone, which was then reduced under Wolff-Kishner conditions, followed by N-methylation of the resulting 2,2,6,6-tetramethylpiperidine with methyl p-toluenesulfonate.
References [ edit ]
^ A. Spinks and E. H. P. Young (1958) Nat. 181 1397
^ G. E. Lee et al. (1958) Nat. 181 1717.
^ a b c d A. Spinks et al. (1958) Br. J. Pharmacol. Chemother. 13 501-520.
^ D. F. Muggleton and H. W.Reading (1959) Br. J. Pharmacol. Chemother. 14 202
^ a b H. K. Hall (1957) J. Am. Chem. Soc. 79 5447-5451.
^ N. J. Leonard and F. P. Hauck (1957) J. Am. Chem. Soc. 79 5279-5292.
^ The "trivial" name of this compound is triacetonamine.
^ The boiling point of 147° given by these authors for their N,2,2,6,6-pentamethylpiperidine (pempidine) is significantly below the range of ~ 182-188° reported by other chemists.
External links [ edit ]
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