256397-07-6Relevant academic research and scientific papers
Amino-benzocycloalkane derivatives
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, (2008/06/13)
Compounds of the formula I wherein R2—C, R3—C, R4—C or R5—C may be replaced by N; and wherein n is 1, 2 or 3; R1is aryl, cycloalkyl or heterocyclyl; R2, R3, R4and R5are independently hydrogen, optionally substituted alkyl, halo, amino, substituted amino, trifluoromethyl, cyano, carboxyl, alkoxycarbonyl, aralkoxycarbonyl, (alkyl, aryl or aralkyl)-thio, (alkyl, aryl or aralkyl)-oxy, acyloxy, (alkyl, aryl or aralkyl)-aminocarbonyloxy; or any two of R2, R3, R4and R5at adjacent positions are alkylenedioxy; R6is hydrogen, optionally substituted alkyl, amino, substituted amino, acylamino, wherein Rais hydrogen or optionally substituted alkyl, Rband Rcare independently hydrogen, optionally substituted alkyl, cycloalkyl, aryl or heterocyclyl; or Rband Rctogether represent lower alkylene or lower alkylene interrupted by O, S, or N—(H, alkyl or aralkyl); Rdis optionally substituted alkyl, cycloalkyl, aryl or heterocyclyl; and Reis optionally substituted alkyl, aryl, heterocyclyl, cycloalkyl, amino or substituted amino; and pharmaceutically acceptable salts thereof; and enantiomers thereof; which are useful as inhibitors of microsomal triglyceride transfer protein (MTP) and of apolipoprotein B (ApoB) secretion.
Diaminoindanes as microsomal triglyceride transfer protein inhibitors
Ksander,DeJesus,Yuan,Fink,Moskal,Carlson,Kukkola,Bilci,Wallace,Neubert,Feldman,Mogelesky,Poirier,Jeune,Steele,Wasvery,Stephan,Cahill,Webb,Navarrete,Lee,Gibson,Alexander,Sharif,Hospattankar
, p. 4677 - 4687 (2007/10/03)
The synthesis and biological activities of biarylamide-substituted diaminoindanes as microsomal triglyceride transfer protein (MTP) inhibitors are described. One of the more potent compounds, 8aR, inhibited both the secretion of apoB from Hep G2 cells and the MTP-mediated transfer of triglycerides between synthetic acceptor and donor liposomes with IC50 values of 0.7 and 70 nM, respectively. In normolipidemic rats and dogs, oral administration of 8aR dose-dependently reduced both plasma triglycerides and total cholesterol. Moreover, in rats and dogs, 8aR also prevented the postprandial rise in plasma triglycerides following a bolus administration of a fat load. Because MTP inhibitors decrease very low density lipoprotein assembly in the liver, the potential for hepatic lipid accumulation was evaluated. In normolipidemic rats, hepatic cholesterol and triglyceride contents were dose-dependently increased by 8aR. However, hepatic lipid accumulation resulted in negligible change in total liver weight and was reversible after withdrawal of the compound.
