Five–membered heterocycles with two heteroatoms – pyrazole and imidazole. Analgesic and other derivatives.
A group of heterocyclic aromatic compounds can be described as derived from pyrrole by replacing one of the ring carbons by second heteroatom. Such five-membered ring heterocycles with two heteroatoms, one of them nitrogen, are called azoles. The group name is retained as base for five-membered aromatic heterocycles with two nitrogen atoms. The combination of heteroatoms nitrogen–oxygen gives oxazole's, and nitrogen–sulfur – thiazoles. These compounds are aza-analogs of pyrrole, furan, and thiophene.
Chemical properties. Acid-base properties. Pyrazole is a weak base. As in pyridine, the nitrogen lone pair is on sp2-hybrid orbital. The greater s-character, in comparison to aliphatic amines, is associated with greater stability and lower basicity. This accounts for a decrease of basicity by several powers of ten. In pyrazole, the basicity is further reduced by the presence of adjacent electronegative nitrogen. In sharp contrast, imidazole appears as abnormally basic for a compound with sp 2-hybridized nitrogen.
Both pyrazole and imidazole behave as ampholites – they can react as proton donors and proton acceptors. Imidazole amphoteric properties are more pronounced due to greater distance between the nitrogen atoms.
Pyrazole derivatives.
Antipyrine (Phenazone, 2,3-dimethyl-1-phenyl-5-pyrazolone) is the first antipyretic drug. It reduces high body temperature in fevers. The compound has also analgesic action (painkiller, relieves pain).
Aminopyrine (Aminophenazone, pyramidone) has analgesic, anti-inflammatory and antipyretic properties. Its antirheumatic action is better than that of salicylate. Aminopyrine is more active than antipyrine and has a longer time of action.
Analgin (Metamizole sodium) is a non-steroidal anti-inflammatory drug (NSAID), commonly used in many countries as a powerful analgesic and antipyretic. Because of the sulfonic acid salt group in the molecule
Imidazole derivatives.
Histamine is derived from histidine by enzymatic decarboxylation. It is a biogenic amine, a powerful vasodilator, normally present in tissue. It is formed in excessive amounts in known as traumatic shock. Histamine is involved in local immune responses. Excess histamine in the synapses triggers an allergic reaction with pain, sneezing, and itching. Histamine is responsible for many of the symptoms associated with hay fever and other allergic states.