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Influence of various central moieties on the hypolipidemic properties of long hydrocarbon chain diols and diacids.
Oniciu, Daniela C; Dasseux, Jean-Louis H; Yang, Jing; Mueller, Ralf; Pop, Emil; Denysenko, Anna; Duan, Caiming; Huang, Tian-Bao; Zhang, Lianhao; Krause, Brian R; Drake, Sandra L; Lalwani, Narendra; Cramer, Clay T; Goetz, Brian; Pape, Michael E; McKee, Andrew; Fici, Gregory J; Lutostanski, Janell M; Brown, Stephen C; Bisgaier, Charles L.
Afiliación
  • Oniciu DC; Esperion Therapeutics, A Division of Pfizer Global Research and Development, 3621 South State Street, 695 KMS Place, Ann Arbor, Michigan 48108, USA. oniciu@yahoo.com
J Med Chem ; 49(1): 334-48, 2006 Jan 12.
Article en En | MEDLINE | ID: mdl-16392818
A series of long (11-15) hydrocarbon chain diols and diacids with various central functional groups and terminal gem-dimethyl or -methyl/aryl substituents was synthesized and evaluated in both in vivo and in vitro assays for its potential to favorably alter lipid disorders including metabolic syndrome. Compounds were assessed for their effects on the de novo incorporation of radiolabeled acetate into lipids in primary cultures of rat hepatocytes, as well as for their effects on lipid and glycemic variables in obese female Zucker fatty rats, Crl:(ZUC)-faBR. The most active compounds were hydroxyl-substituted symmetrical diacids and diols with a 13-atom chain and terminal gem-dimethyl substituents. Furthermore, biological activity was enhanced by central substitution with O, C=O, S, S=O compared to the methylene analogues and was diminished for compounds with central functional groups such as carbamate, ester, urea, acetylmethylene, and hydroxymethylene.
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Diabetes Mellitus Experimental / Ácidos Dicarboxílicos / Alcoholes / Hidrocarburos / Hiperlipidemias / Hipolipemiantes Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: J Med Chem Asunto de la revista: QUIMICA Año: 2006 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Diabetes Mellitus Experimental / Ácidos Dicarboxílicos / Alcoholes / Hidrocarburos / Hiperlipidemias / Hipolipemiantes Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: J Med Chem Asunto de la revista: QUIMICA Año: 2006 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos