title: Vicinal diaryl azole-based urea derivatives as potential cholesterol lowering agents acting through inhibition of SOAT enzymes.
abstract: A novel series of vicinal diaryl azole-urea derivatives were synthesized and evaluated for their potential to inhibit SOAT enzyme. Among the reported compounds, compound (12d) emerged as the most potent compound with an IC50value of 2.43 μM. In polaxamer-407 induced lipoprotein lipase inhibition model, compound (12d) reduced triglyceride turnover in vivo. Compound (12d) also showed dose-dependent prevention of serum total cholesterol and prevention of LDL-C elevation at a dose of 30 mg/kg. Furthermore, compound (12d) showed potential to stop falling levels of serum HDL-C dose-dependently and improved the atherogenic index. Effect of 12d on body weight, plaque formation and development of atherogenic lesions were studied. Toxicological study of compound (12d) indicated that at a dose of 2000 mg/kg, 12d was devoid of any signs of toxicity or mortality.
authors.affiliation: Faculty of Pharmacy, Kalabhavan Campus, The Maharaja Sayajirao University of Baroda, Vadodara, 390001, India.
authors.forename: Palash
authors.initials: P
authors.lastname: Pal
authors.affiliation: Faculty of Pharmacy, Kalabhavan Campus, The Maharaja Sayajirao University of Baroda, Vadodara, 390001, India.
authors.forename: Hardik P
authors.initials: HP
authors.lastname: Gandhi
authors.affiliation: Faculty of Pharmacy, Kalabhavan Campus, The Maharaja Sayajirao University of Baroda, Vadodara, 390001, India.
authors.forename: Ashish M
authors.initials: AM
authors.lastname: Kanhed
authors.affiliation: Faculty of Pharmacy, Kalabhavan Campus, The Maharaja Sayajirao University of Baroda, Vadodara, 390001, India.
authors.forename: Nirali R
authors.initials: NR
authors.lastname: Patel
authors.affiliation: Faculty of Pharmacy, Kalabhavan Campus, The Maharaja Sayajirao University of Baroda, Vadodara, 390001, India.
authors.forename: Niraj N
authors.initials: NN
authors.lastname: Mankadia
authors.affiliation: Faculty of Pharmacy, Kalabhavan Campus, The Maharaja Sayajirao University of Baroda, Vadodara, 390001, India.
authors.forename: Satish N
authors.initials: SN
authors.lastname: Baldha
authors.affiliation: Faculty of Pharmacy, Kalabhavan Campus, The Maharaja Sayajirao University of Baroda, Vadodara, 390001, India.
authors.forename: Mahesh A
authors.initials: MA
authors.lastname: Barmade
authors.affiliation: Faculty of Pharmacy, Kalabhavan Campus, The Maharaja Sayajirao University of Baroda, Vadodara, 390001, India.
authors.forename: Prashant R
authors.initials: PR
authors.lastname: Murumkar
authors.affiliation: Faculty of Pharmacy, Kalabhavan Campus, The Maharaja Sayajirao University of Baroda, Vadodara, 390001, India. Electronic address: mryadav11@yahoo.co.in.
authors.forename: Mange Ram
authors.initials: MR
authors.lastname: Yadav
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000737:chemistry* / Q000494:pharmacology; D050197:Atherosclerosis / Q000517:prevention & control; D001393:Azoles / Q000737:chemistry / Q000494:pharmacology*; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology; D008071:Lipoprotein Lipase / Q000037:antagonists & inhibitors; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors*; D014280:Triglycerides / Q000097:blood; D014508:Urea / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000924:Anticholesteremic Agents; D001393:Azoles; D008078:Cholesterol, LDL; D004791:Enzyme Inhibitors; D000960:Hypolipidemic Agents; D014280:Triglycerides; D014508:Urea; D002784:Cholesterol; D002785:Sterol O-Acyltransferase; D008071:Lipoprotein Lipase
keywords: Atherosclerosis; Cholesterol lowering agents; SOAT inhibitors; Vicinal diaryl compounds