A series of 1,3-dicarbonyl compounds having 2(3H)-benzazolonic heterocycles has been synthesized and tested for PPARgamma agonist activity. SAR were developed and revealed that 6-acyl-2(3H)-benzothiazolone derivatives with 1,3-dicarbonyl group were the most potent. IP administration of compound 22 exhibited comparable levels of glucose and triglyceride correction to PO administration of rosiglitazone in the ob/ob mouse studies.
View Article and Find Full Text PDFWith a view to specifying structure-activity relationships we have synthesised a new series of analogues of the Rho-kinase inhibitor 1-(5-isoquinolinesulfonyl)-homopiperazine (Fasudil). The structural modifications concerned the isoquinolinyl heterocycle and the sulfonyl group which are the two main features of this lead compound. These analogues were evaluated on the actin cytoskeleton and on the enzymatic activity of Rho-kinase.
View Article and Find Full Text PDFJ Enzyme Inhib Med Chem
December 2002
In order to specify structure-activity relationships we have synthesized new series of analogues of the Rho-kinase inhibitor (R)-(+)-N-(4-pyridyl)-4-(1-aminoethyl)benzamide (Y-32885). The structural modifications concerned the 1-aminoethyl, the pyridyl and the amide groups which are the main features of this lead compound. Our analogue derivatives were evaluated on GTPgammaS-induced contraction in permeabilized smooth-muscle and on the actin cytoskeleton.
View Article and Find Full Text PDFA series of N-(2-phenylbenzofuran-3-yl) ethyl amide and N-(2-arylalkylbenzofuran-3-yl) ethyl amide derivatives were synthesized and evaluated as melatonin receptor ligands. The affinity of each compound for the two MT(1) and MT(2) melatonin receptor subtypes was determined by binding studies using 2-[(125)I]iodomelatonin on human embryonic kidney cell line HEK293 membrane homogenates. The intrinsic activity of the most interesting compounds was evaluated on the [(35)S]GTPgammaS binding assay.
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