BORON ANALOGS OF AMINO-ACIDS .6. SYNTHESIS AND CHARACTERIZATION OF DIPEPTIDE AND TRIPEPTIDE ANALOGS AS ANTINEOPLASTIC, ANTIINFLAMMATORY AND HYPOLIPIDEMIC AGENTS

A number of boron-containing dipeptides with the general formulation Me3NBH2C(O)NHCH(R)COOR′ and a tripeptide, Me3NBH2C(O)NHCH2C(O)NHCH2COOEt were synthesized by condensation of Me3NBH2COOH with the corresponding NH2CH(R)COOR′ (NH2CH2C(O)NHCH2COOEt in case of tripeptide) in the presence of PPh3 and CCl4. Further reaction with liquid NH3 afforded NH3BH2C(O)NHCH(R)CONH2 (NH3BH2C(O)NHCH2C(O)NHCH2C(O)NH2 in the case of tripeptide) or NH3BH2C(O)NHCH(R)COOMe. These peptides proved to have antineoplastic, anti-inflammatory and hypolipidemic activity in mice. The antineoplastic activity was weak. The anti-inflammatory activity was similar to that of phenylbutazone, although at a lower dosage, ie 8 mg/kg × 2 was required for activity. IC50 values were in the range of 7.0-29.0 mg/kg × 2. The compounds were most effective as hypolipidemic agents, significantly lowering both serum cholesterol and triglyceride levels at a dose of 8 mg/kg per day. After 16 days administration, this activity was far superior to known clinical therapeutic agents used to treat atherosclerosis. © 1990.