Document Report Card

ID: ALA1134532

Journal: J Med Chem

Title: Reversible carnitine palmitoyltransferase inhibitors with broad chemical diversity as potential antidiabetic agents.

Authors: Giannessi F, Chiodi P, Marzi M, Minetti P, Pessotto P, De Angelis F, Tassoni E, Conti R, Giorgi F, Mabilia M, Dell'Uomo N, Muck S, Tinti MO, Carminati P, Arduini A.

Abstract: A series of carnitine related compounds of general formula XCH(2)CHZRCH(2)Y were evaluated as CPT I inhibitors in intact rat liver (L-CPT I) and heart mitochondria (M-CPT I). Derivative 27 (ZR = -HNSO(2)R, R = C(12), X = trimethylammonium, Y = carboxylate, (R) form) showed the highest activity (IC(50) = 0.7 microM) along with a good selectivity (M-CPT I/L-CPTI IC(50) ratio = 4.86). Diabetic db/db mice treated orally with 27 showed a significant reduction of serum glucose levels.

CiteXplore: 11448219

DOI: 10.1021/jm010889+