Antihistamine precursor

Cyclodehydration has been used to prepare the antihistamine precursor 80 under... 

Histidine is characterized by a heterocyclic side chain known as imidazole. The imidazole group will bear a positive charge under physiological conditions. Histidine is the metabolic precursor to histamine, a potent inflammatory molecule. Antihistamines work by antagonizing the action of histamine. 

An important group of antihistamines, the pheniramines (92), use 2-chloropyridine as a basic feedstock. The activity of chlorpheniramine (92 X = Cl) as an H receptor blocker has recently been reported (79MI20906). Zimelidine (93), a relatively new compound of related structure, exhibits antidepressant activity with reduced subjective side-effects found with other antidepressants (79MI20907). 2-Halopyridines also function as precursors to another group of antihistamines exemplified by p-bromotripelennamine (94) (51USP2572569). 

The Chemical Diversion and Trafficking Act of 1988 defines precursor chemicals that can be used in the process of producing illicit drugs. Companies producing or supplying such chemicals must keep certain records and report orders that are suspicious or above a specified size prior to delivery. The Domestic Chemical Diversion Control Act of 1993 further e.xpanded these controls, dealing particularly with the diversion of ephedrine (found in over-the-counter antihistamines) to the production of methamphetamines ( speed ). 

We have already discussed the importance of heterocycKc systems in many biological compounds. The final group to consider is the amino acid family from which aU proteins are constmcted. Three heterocycKc compounds, of a simple but profoundly important stracture, are found in this family histidine, proKne, and tryptophan. Histidine on biological decarboxylation is the precursor of the notorious histamine, which is the cause of much human discomfort and of the creation of a vast family of pharmaceuticals called antihistamines. 

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