Showing papers in "Bioorganic & Medicinal Chemistry Letters in 1998"

TL;DR: Potent and selective dipeptidyl boronic acid proteasome inhibitors are described, which are promising new therapeutics for treatment of cancer and inflammatory diseases.

TL;DR: In search of antiinflammatory drugs with a new mechanism of action, U0126 was found to functionally antagonize AP-1 transcriptional activity via noncompetitive inhibition of the dual specificity kinase MEK with an IC50 of 0.07 microM.

TL;DR: A 9-mer phosphorothioate-LNA containing three LNA thymine monomers were able to recognize both complementary DNA and RNA with thermal affinities comparable to those of parent LNA.

TL;DR: A series of substituted chalcones was synthesised and screened for cytotoxic activity against the K562 human leukaemia cell line and (E)-3-(3"-Hydroxy-4"-methoxyphenyl)-2-methyl-1-(3',4',5'- trimethoxyl)-prop-2-en-1-one [IC50 (K562) 0.21 nM] was found to be the most active.

TL;DR: Calophyllum cerasiferum contained (-)-calanolide B as its major coumarin constituent in significant amount and thus constitute a renewable source of this compound.

TL;DR: 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO) was 400 times more potent than previous compounds made as an inhibitor of production of nitric oxide induced by interferon-gamma in mouse macrophages.

TL;DR: A series of novel substituted 2-cyanoquinolines have been synthesized and the structure activity relationships were evaluated with respect to their ability to inhibit the formation of leukotrienes via the 5-lipoxygenase enzyme.

TL;DR: Structural-activity studies on Ac-DDIVPC-OH revealed that side chains of the P4, P3 and P1 residues contribute the most to binding and that the introduction of a D-amino acid at the P5 position improves potency considerably.

TL;DR: A series of lysosomal protease-sensitive peptides attached to doxorubicin was prepared as model substrates for internalizing anticancer immunoconjugates and potential antimetastasis prodrugs.

TL;DR: A series of cis-restricted combretastatin analogues with 5-membered heterocycles were synthesized and their inhibitory activity against microtubule assembly and cytotoxic activity against the colon 26 adenocarcinoma cancer cell line were evaluated.

TL;DR: Design and synthesis of a series of very potent nonpeptide HIV protease inhibitors are described, derived from novel high affinity P2-ligands and (R)-(hydroxyethylamino)sulfonamide isostere.

TL;DR: Two new fluorinated fluorescent dyes, 6,8-difluoro-7-hydroxy-4-methylcoumarin (Marina Blue) and 3-carboxy-6,8 -diffluoro- 7-Hydroxycou marin (Pacific Blue), exhibit excellent photophysical properties among a series of novel fluorinated 7-hydroxylated coumarins, making them superior fluorescent dye for use as reporter molecules in biological systems.

TL;DR: Investigations led to the discovery of a series of isoindolinones having D4 affinity that were identified as a potent dopamine D4 ligand and replaced the benzylic alcohol with a metabolically more stable moiety.

TL;DR: The majority of chalcones synthesized and evaluated showed anti-inflammatory effects in the mouse air pouch model and only four compounds inhibited cyclo-oxygenase-2 activity.

TL;DR: Hepatoprotective sesquiterpenes were isolated from the aqueous acetone extract of Zedoariae Rhizoma, the rhizome of Curcuma zedoaria ROSCOE and found to show potent protective effect on D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced acute liver injury in mice.

TL;DR: Substrates containing doxorubicin, paclitaxel, and mitomycin C attached to the cathepsin B-sensitive dipeptide Phe-Lys via a self-immolative spacer were prepared as model compounds for internalizing anticancer immunoconjugates.

TL;DR: N-Phthaloyl 3-amino-3-arylpropionic acid analogs of thalidomide that are potent inhibitors of tumor necrosis factor-alpha are reported.

TL;DR: SAR in a series of monocyclic beta-lactam N-ureas, has defined the size and relative stereochemistry of the C-3 substituent producing a low micromolar inhibitor 17b with good aqueous stability and selectivity over the mammalian serine proteases.

TL;DR: This preliminary investigation demonstrates that simple modifications of the parent structure of betulinic acid can produce potentially important derivatives, which may be developed as antitumor drugs.

TL;DR: Investigation of furans, pyrroles and pyrazolones identified 3-pyridyl-2,5-diaryl-p Pyrroles as potent, orally bioavailable inhibitors of p38 kinase.

TL;DR: Evidence is provided that resveratrol is capable of binding to DNA, and that the Cu(2+)-dependent DNA damage is more likely caused by a copper-peroxide complex rather than by a freely diffusible oxygen species.

TL;DR: 5- Chloro-3-(4-methylsulfonyl)phenyl-2-(2-methyl-5-pyridinyl)pyridine 33 was identified as the optimum compound in this series and observed to inhibit COX-2 activity by introducing a substituent at C5 of the central pyridine.

TL;DR: Pyrimidine analogs of the pyrimidinylimidazole class of CSBP/p38 kinase inhibitors were prepared in an effort to reduce the potent inhibition of hepatic cytochrome P450 observed for the pyridinyl compounds.

TL;DR: The 3-dimensional structure of one of the most potent analogs in this series, 10d, was determined by X-ray crystallography and suggests the spatial requirements for potent CRF-1 receptor binding affinity in thisseries of 3-phenylpyrazolo[1,5-a]pyrimidines.

TL;DR: A series of 2(1H)-pyrrolidino[3,2-g]quinolinones was prepared and tested for the ability to modulate the transcriptional activity of the human androgen receptor (hAR), and more substituted analogues, particularly 6,7-disubstituted compounds, were potent hAR agonists in vitro.

TL;DR: An efficient method for solid-phase synthesis of pyrroles is described and pyrrole-3-carboxamides are obtained in excellent purity.

TL;DR: The synthesis and biological activity of a series of 3,6-substituted quinazolinediones and quinzolinones demonstrates the utility of these structures as central templates for nonpeptide RGD mimics.

TL;DR: Norvaline was identified as a chemically stable replacement for the P1 residue of Ac-DDIVPC-OH which was also compatible with activated carbonyl functionalities.

TL;DR: Synthesis and biological evaluation of new chrysene derivatives aimed at the development of anticancer agents were carried out.

TL;DR: It is shown, that 4( 5)-carboxyfluorescein is much more efficient than the hitherto predominantly utilized reagents 4(5)-car boxyfluorscein-N-succinimidylester and 4(4)-fluorescesceinisothiocyanate.