Synthesis and biological evaluation of ester prodrugs of Benzafibrate as orally active hypolipidemic agents.
A series of bezafibrate ester prodrugs 1-7 were synthesized and evaluated for hypolipidemic activity in Swiss Albino mice (SAM). Bezafibrate (1a), a hypolipidemic drug was used as a reference compound for data comparison. Among the synthesized compounds, prodrug 7 showed superior activities in decreasing triglyceride up to 30% in mice plasma after oral administration of 50mg/kg/day for 8 days. Prodrugs 2, 3, 5, 6, and 7 were found to be more lipophilic than bezafibrate (1a), indicated by partition coefficients measured in octanol-buffer system at pH 7.4. On the basis of in vivo studies, prodrug 7 emerged as new potent hypolipidemic agent.
Medicinal Chemistry Research Laboratory, School of Chemical Sciences, Solapur University, Solapur 413 255, Maharashtra, India. bandgar_bp@yahoo.com
Babasaheb P
BP
Bandgar
Rajendra J
RJ
Sarangdhar
Khan
K
Fruthous
Jeyamurugan
J
Mookkan
Shilpee
S
Chaudhary
Hemant V
HV
Chavan
Sunil B
SB
Bandgar
Vinayak Y
VY
Kshirsagar
D000284:Administration, Oral; D000818:Animals; D001629:Bezafibrate / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D004334:Drug Administration Schedule; D004355:Drug Stability; D004952:Esters; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D000960:Hypolipidemic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D008297:Male; D051379:Mice; D000442:Octanols; D011355:Prodrugs / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014280:Triglycerides / Q000097:blood; D014867:Water
D004952:Esters; D000960:Hypolipidemic Agents; D000442:Octanols; D011355:Prodrugs; D014280:Triglycerides; D014867:Water; D001629:Bezafibrate