0000000000624807

AUTHOR

Pekka Poutiainen

showing 3 related works from this author

Discovery of 5-benzyl-3-phenyl-4,5-dihydroisoxazoles and 5-benzyl-3-phenyl-1,4,2-dioxazoles as potent firefly luciferase inhibitors.

2013

Luciferase reporter assays are commonly used in high-throughput screening methods. Here, we report new firefly luciferase (FLuc) inhibitors based on 5-benzyl-3-phenyl-4,5-dihydroisoxazoles and 5-benzyl-3-phenyl-1,4,2-dioxazoles, which showed up as "false positives" in a luciferase reporter gene-based assay for nuclear receptor antagonists. The inhibition was shown to be noncompetitive for both natural enzyme substrates (d-luciferin and ATP) and selective to FLuc and proven to arise from a direct interaction between the enzyme and the inhibitor. Of the 63 evaluated compounds, 28 showed significantly better inhibition potency than the well-known inhibitor resveratrol (IC(50) = 59 nM), with fi…

AzolesModels MolecularMagnetic Resonance SpectroscopyStereochemistryDrug Evaluation PreclinicalResveratrolCell Linechemistry.chemical_compoundInhibitory Concentration 50Drug DiscoveryScreening methodIc50 valuesPotencyAnimalsLuciferaseEnzyme InhibitorsLuciferasesIC50ta116chemistry.chemical_classificationFirefliesEnzymechemistryNuclear receptorBiochemistryMolecular MedicineJournal of medicinal chemistry
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Design, synthesis, and biological evaluation of nonsteroidal cycloalkane[d]isoxazole-containing androgen receptor modulators.

2012

We report here the design, preparation, and systematic evaluation of a novel cycloalkane[d]isoxazole pharmacophoric fragment-containing androgen receptor (AR) modulators. Cycloalkane[d]isoxazoles form new core structures that interact with the hydrophobic region of the AR ligand-binding domain. To systematize and rationalize the structure-activity relationship of the new fragment, we used molecular modeling to design a molecular library containing over 40 cycloalkane[d]isoxazole derivatives. The most potent compound, 4-(3a,4,5,6,7,7a-hexahydrobenzo[d]isoxazol-3-yl)-2-(trifluoromethyl)benzonitrile (6a), exhibits antiandrogenic activity significantly greater than that of the most widely used …

Models MolecularBicalutamideMolecular modelStereochemistryProtein ConformationChemistry Techniques Syntheticchemistry.chemical_compoundStructure-Activity RelationshipDrug DiscoveryChlorocebus aethiopsmedicineAnimalsIsoxazoleNonsteroidal Anti-AndrogensTrifluoromethylta1182CycloparaffinsIsoxazolesAndrogen receptorCycloalkaneBenzonitrilechemistryReceptors AndrogenDrug DesignCOS CellsMolecular MedicineHydroxyflutamidemedicine.drugJournal of medicinal chemistry
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Comprehensive Strategy for Proton Chemical Shift Prediction: Linear Prediction with Nonlinear Corrections

2014

A fast 3D/4D structure-sensitive procedure was developed and assessed for the chemical shift prediction of protons bonded to sp3carbons, which poses the maybe greatest challenge in the NMR spectral parameter prediction. The LPNC (Linear Prediction with Nonlinear Corrections) approach combines three well-established multivariate methods viz. the principal component regression (PCR), the random forest (RF) algorithm, and the k nearest neighbors (kNN) method. The role of RF is to find nonlinear corrections for the PCR predicted shifts, while kNN is used to take full advantage of similar chemical environments. Two basic molecular models were also compared and discussed: in the MC model the desc…

business.industryComputer scienceGeneral Chemical EngineeringMonte Carlo methodLinear predictionGeneral ChemistryLibrary and Information SciencesMachine learningcomputer.software_genreComputer Science ApplicationsRandom forestk-nearest neighbors algorithmMolecular dynamicsNonlinear systemPrincipal component regressionArtificial intelligenceStatistical physicsbusinessConformational isomerismcomputerta116Journal of Chemical Information and Modeling
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