caa a22 4500 465765823 CHVBK 20180323111913.0 cr unu---uuuuu 170327e19900701xx s 000 0 eng 10.1007/BF02537982 doi (NATIONALLICENCE)springer-10.1007/BF02537982 Structure activity relationships of imido N -alkyl semicarbazones, thiosemicarbazones and acethydrazones as hypolipidemic agents in rodents [Elektronische Daten] [James Chapman Jr., Pierre DeLucy, Oi Wong, Iris Hall] A series of nitrogen substitutedN-butan-3-one derivatives of cyclic imides (phthalimide, substituted phthalimide,o-benzosulfimide, 1,8-naphthalimide, 2,3-dihydrophthalazine-1,4-dione and diphenimide) and their semicarbazone, thiosemicarbazone and acethydrazone derivatives were investigated for hypolipidemic activity in rodents. These compounds were generally potent hypolipidemic agents, lowering serum cholesterol levels on an average of 37% and serum triglyceride levels on an average of 29% after 16 days dosing at 20 mg/kg day intraperitoneally (I.P.) in mice. Several analogs, most notably the semicarbazone and acethydrazone derivatives of 1-N-(1,8-naphthalimido)-butan-3-one, demonstrated improved hypocholesterolemic activity relative to their ketone percursors. Similarly, the acethydrazone derivatives generally resulted in improved hypotriglyceridemic activity in each series of 2-(3-oxobutyl)-2,3-dihydrophthalazone-1,4-dione analogs tested. The thiosemicarbazones in mice generally resulted in a loss in hypolipidemic activity. Select compounds, 1-N-3-methylphthalimido butan-3-semicarbazone (Ig) and 1-(4-methoxyphthalazine-1(2H)-one)yl butan-3(N-acetyl)hydrazone (IVg), at 10 mg/kg/day orally administered to rats demonstrated potent hypolipidemic activity after 14 days. These compounds lowered liver, small intestine mucosa and aorta wall tissue lipids, e.g. cholesterol and triglycerides, and raised fecal excretion of cholesterol moderately and of triglyceride significantly. Rat serum lipoprotein fractions after treatment for 14 days showed that the two agents lowered VLDL cholesterol and raised HDL cholesterol content. American Oil Chemists' Society, 1990 Chapman Jr. James Department of Basic Pharmaceutical Sciences, College of Pharmacy, University of South Carolina, 29208, Columbia, SC aut DeLucy Pierre Department of Basic Pharmaceutical Sciences, College of Pharmacy, University of South Carolina, 29208, Columbia, SC aut Wong Oi Division of Medicinal Chemistry & Natural Products, School of Pharmacy, University of North Carolina, 27599, Chapel Hill, NC aut Hall Iris Division of Medicinal Chemistry & Natural Products, School of Pharmacy, University of North Carolina, 27599, Chapel Hill, NC aut Lipids Springer-Verlag 25/7(1990-07-01), 391-397 0024-4201 25:7<391 1990 25 11745 https://doi.org/10.1007/BF02537982 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF02537982 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Chapman Jr James Department of Basic Pharmaceutical Sciences, College of Pharmacy, University of South Carolina, 29208, Columbia, SC aut NATIONALLICENCE 700 1- DeLucy Pierre Department of Basic Pharmaceutical Sciences, College of Pharmacy, University of South Carolina, 29208, Columbia, SC aut NATIONALLICENCE 700 1- Wong Oi Division of Medicinal Chemistry & Natural Products, School of Pharmacy, University of North Carolina, 27599, Chapel Hill, NC aut NATIONALLICENCE 700 1- Hall Iris Division of Medicinal Chemistry & Natural Products, School of Pharmacy, University of North Carolina, 27599, Chapel Hill, NC aut NATIONALLICENCE 773 0- Lipids Springer-Verlag 25/7(1990-07-01), 391-397 0024-4201 25:7<391 1990 25 11745 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer