Pempidine is a ganglion-blocking drug, first reported in 1958 by two research groups working independently, and introduced as an oral treatment for hypertension.

Pharmacology

Reports on the "classical" pharmacology of pempidine have been published. The Spinks group, at ICI, compared pempidine, its ''N''-ethyl analogue, and

mecamylamine Mecamylamine ( INN, BAN; or mecamylamine hydrochloride (USAN); brand names Inversine, Vecamyl) is a non-selective, non-competitive antagonist of the nicotinic acetylcholine receptors (nAChRs) that was introduced in the 1950s as an antihypertensi ...

in considerable detail, with additional data related to several structurally simpler compounds.

Toxicology

LD₅₀ for the HCl salt of pempidine in mice: 74 mg/kg (i.v.); 125 mg/kg (i.p.); 413 mg/kg (p.o.).

Chemistry

Pempidine is an

aliphatic In organic chemistry, hydrocarbons ( compounds composed solely of carbon and hydrogen) are divided into two classes: aromatic compounds and aliphatic compounds (; G. ''aleiphar'', fat, oil). Aliphatic compounds can be saturated, like hexane, ...

, sterically hindered, cyclic,

tertiary Tertiary ( ) is a widely used but obsolete term for the geologic period from 66 million to 2.6 million years ago. The period began with the demise of the non-avian dinosaurs in the Cretaceous–Paleogene extinction event, at the start ...

amine In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen Hydrogen is the chemical element wi ...

, which is a

weak base A weak base is a base that, upon dissolution in water, does not dissociate completely, so that the resulting aqueous solution contains only a small proportion of hydroxide ions and the concerned basic radical, and a large proportion of undissociat ...

: in its

protonated In chemistry, protonation (or hydronation) is the adding of a proton (or hydron, or hydrogen cation), (H+) to an atom, molecule, or ion, forming a conjugate acid. (The complementary process, when a proton is removed from a Brønsted–Lowry acid, ...

form it has a p''K''_a of 11.25. Pempidine is a liquid with a boiling point of 187–188 °C and a density of 0.858 g/cm³. Two early syntheses of this compound are those of Leonard and Hauck, and Hall. These are very similar in principle: Leonard and Hauck reacted

phorone Phorone, or diisopropylidene acetone, is a yellow crystalline substance with a geranium odor, with formula or . Preparation It was first obtained in 1837 in impure form by the French chemist Auguste Laurent, who called it "camphoryle". In 1849, ...

with

ammonia Ammonia is an inorganic compound of nitrogen and hydrogen with the formula . A stable binary hydride, and the simplest pnictogen hydride, ammonia is a colourless gas with a distinct pungent smell. Biologically, it is a common nitrogenous wa ...

, to produce 2,2,6,6-tetramethyl-4-piperidone, which was then reduced by means of the

Wolff–Kishner reduction The Wolff–Kishner reduction is a reaction used in organic chemistry to convert carbonyl functionalities into methylene groups. In the context of complex molecule synthesis, it is most frequently employed to remove a carbonyl group after it has se ...

to 2,2,6,6-tetramethylpiperidine; this secondary amine was then ''N''-methylated using methyl iodide and

potassium carbonate Potassium carbonate is the inorganic compound with the formula K2 CO3. It is a white salt, which is soluble in water. It is deliquescent, often appearing as a damp or wet solid. Potassium carbonate is mainly used in the production of soap and gl ...

.The boiling point of 147 °C given by these authors for their ''N'',2,2,6,6-pentamethylpiperidine (pempidine) is significantly below the range of ~182–188 °C reported by other chemists. Hall's method involved reacting

acetone Acetone (2-propanone or dimethyl ketone), is an organic compound with the formula . It is the simplest and smallest ketone (). It is a colorless, highly volatile and flammable liquid with a characteristic pungent odour. Acetone is miscib ...

with ammonia in the presence of

calcium chloride Calcium chloride is an inorganic compound, a salt with the chemical formula . It is a white crystalline solid at room temperature, and it is highly soluble in water. It can be created by neutralising hydrochloric acid with calcium hydroxide. Ca ...

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

External links

* {{Nicotinic acetylcholine receptor modulators Nicotinic antagonists Piperidines Reagents for organic chemistry