Novel pyrimidine and 1,3,5-triazine hypolipidemic agents

Area of Science:

• Medicinal Chemistry
• Pharmacology

Background:

• Trisubstituted pyrimidines show promise as hypolipidemic agents.
• A known compound, [[4-chloro-6-[(2,3-dimethylphenyl)amino]-2-pyrimidinyl]thio] acetic acid, effectively lowers lipids but causes significant hepatomegaly.

Purpose of the Study:

• To synthesize novel trisubstituted pyrimidine derivatives.
• To mitigate the hepatomegaly-inducing effect while preserving hypolipidemic activity.

Main Methods:

• Chemical synthesis of new pyrimidine compounds by altering substituents.
• In vivo evaluation of hypolipidemic effects and liver health.

Main Results:

• Compound 14b (4-chloro-2-(dimethylamino)-6-[(2,3-dimethylphenyl)amino]pyrimidine) eliminated hepatomegaly and reduced triglycerides.
• Compound 18b ([[4-chloro-6-[(2,3-dimethylphenyl)amino]-2-pyrimidinyl]amino] acetic acid) reduced hepatomegaly and significantly lowered both cholesterol and triglycerides.
• Both compounds retained significant hypolipidemic properties.

Conclusions:

• Structural modification of trisubstituted pyrimidines can successfully reduce hepatotoxicity.
• Novel derivatives offer a potentially improved therapeutic profile for managing dyslipidemia.