478363-91-6Relevant academic research and scientific papers
DIACYLGLYCEROL ACYLTRANSFERASE INHIBITORS
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, (2009/01/20)
Provided herein are compounds of the formula (I) as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of diseases such as, for example, obesity, type II diabetes mellitus and metabolic syndrome.
Structure activity relationships of new inhibitors of mammalian 2,3-oxidosqualene cyclase designed from isoquinoline derivatives
Binet, Jean,Thomas, Didier,Benmbarek, Abdellah,De Fornel, Daniel,Renaut, Patrice
, p. 316 - 329 (2007/10/03)
We have designed more potent inhibitors from the previously reported LF 05-0038, a 6-isoquinolinol based inhibitor of 2,3-oxidosqualene cyclase (IC 50: 1.1 μM). Replacement of the 3-OH group by various 3-substituted amino groups, and modification of the alkyl chain borne by the endocyclic nitrogen led to inhibitors with IC50 in the range of 0.15 to 1 μM. In a second step, opening of the bicyclic ring system afforded the corresponding aminoalkylpiperidines which were slightly more potent. Finally, introduction of suitable aromatic containing moieties on the piperidine nitrogen yielded very potent inhibitors such as 20x (IC50=18 nM) easy to synthesize and achiral. The recent availability of the crystal structure of squalene-hopene cyclase allowed us to construct a three-dimensional (3D) model of the related 2,3-oxidosqualene cyclase (OSC) which was tentatively used to describe the possible mode of binding of our compounds and which can be useful for designing new inhibitors.
