Structure
Chemical Formula - C19H23ClN2
Mode of action
To the histamine H1 receptor, triprolidine binds. The negative feelings caused by histamine are momentarily reduced because of this blocking, the activity of endogenous histamine.
Structure-Activity Relationship (SAR) of Triprolidine Hydrochloride
Triprolidine hydrochloride is a first-generation antihistamine known for its effectiveness in treating allergic symptoms.
The SAR of triprolidine can be dissected as follows:
1. Pyrrolidine Ring:
Triprolidine contains a pyrrolidine ring, a five-membered nitrogen-containing ring. This ring structure is crucial for the histamine H1 receptor antagonistic activity. The pyrrolidine ring imparts a higher degree of selectivity and potency compared to other ring structures in antihistamines.
2. Phenyl Ring Substitution:
The presence of two phenyl rings directly attached to the central nitrogen of the pyrrolidine ring is essential for its antihistaminic activity. The specific orientation and spacing of these rings contribute significantly to the drug's affinity for the H1 receptor.
3. Substitution on Phenyl Rings:
The substitution pattern on the phenyl rings, particularly the presence of a chloro group, influences the potency and selectivity of the drug. Chlorine atoms increase the lipophilicity and hence the ability to cross the blood-brain barrier, contributing to sedative effects.
4. Hydrochloride Salt Form:
As with many similar drugs, the hydrochloride (HCl) salt form of triprolidine enhances its water solubility, making it more amenable for oral administration and rapid absorption.
5. Tertiary Amine:
The tertiary amine (part of the pyrrolidine ring) is key to the anticholinergic activity, contributing to the side effects commonly associated with first-generation antihistamines.
Synthesis of Triprolidine Hydrochloride
The synthesis of triprolidine hydrochloride involves several steps, starting from basic organic compounds. A simplified version of this synthesis can be described as follows:
1. Formation of the Pyrrolidine Ring:
The synthesis often starts with the formation of a pyrrolidine ring, which can be derived from pyrrolidine itself or other precursors.
2. Arylation:
The pyrrolidine ring is then arylated with a phenyl or substituted phenyl compound. This can involve a Friedel-Crafts acylation or other types of aromatic substitution reactions.
3. Introduction of Chlorine:
If not already present in the aromatic precursor, a chlorine atom is introduced into the aromatic ring through halogenation reactions.
4. Formation of Triprolidine:
The resulting compound, after proper functional group manipulations and ring closures, yields triprolidine.
5. Formation of the Hydrochloride Salt:
Finally, the free base form of triprolidine is converted into its hydrochloride salt, typically by treatment with hydrochloric acid.
Triprolidine (free base) + HCl → Triprolidine hydrochloride
The synthesis of triprolidine hydrochloride can vary in complexity and specific reagents used, depending on the starting materials and desired yield and purity. The synthesis is characterized by its focus on creating the specific ring structure and substituents that confer triprolidine's antihistaminic properties.
Uses
Triprolidine is used to treat watery eyes, hay fever, the common cold, and allergies, whimpering and sneezing.