45 research outputs found
ChemInform Abstract: A New Concise Synthesis of 2,3‐Dihydroquinazolin‐4(1H)‐one Derivatives.
No full textA microwave-assisted, propylphosphonic anhydride (T3P®) mediated one-pot Fischer indole synthesis
No full textA rapid, mild, and high yielding protocol for the Fischer indolization of arylhydrazines with T3P (R) under microwave irradiation is described. Significant features of this method include short reaction times and preparative ease.</p
ChemInform Abstract: A Microwave-Assisted, Propylphosphonic Anhydride (T3P®) Mediated One-Pot Fischer Indole Synthesis.
No full textCrystal structure of human MTH1 and the 8-oxo-dGMP product complex
No full textMTH1 hydrolyzes oxidized nucleotide triphosphates, thereby preventing them from being incorporated into DNA. We here present the structures of human MTH1 (1.9 angstrom) and its complex with the product 8-oxo-dGMP (1.8 angstrom). Unexpectedly MTH1 binds the nucleotide in the anti conformation with no direct interaction between the 8-oxo group and the protein. We suggest that the specificity depends on the stabilization of an enol tautomer of the 8-oxo form of dGTP. The binding of the product induces no major structural changes. The structures reveal the mode of nucleotide binding in MTH1 and provide the structural basis for inhibitor design.authorCount :7</p
Validating Signal Transducer and Activator of Transcription (STAT) ProteinInhibitor Interactions Using Biochemical and Cellular Thermal Shift Assays
No full textStructure–metabolism-relationships in the microsomal clearance of piperazin-1-ylpyridazines
No full textIn this study, we provide insight into the metabolic profile of a series of piperazin-1-ylpyridazines suffering from rapid in vitro intrinsic clearance in a metabolic stability assay using liver microsomes.</p
Exploring drug target flexibility using in situ click chemistry: Application to a mycobacterial transcriptional regulator
No full textIn situ click chemistry has been successfully applied to probe the ligand binding domain of EthR, a mycobacterial transcriptional regulator known to control the sensitivity of Mycobacterium tuberculosis to several antibiotics. Specific protein-templated ligands were generated in situ from one azide and six clusters of 10 acetylenic fragments. Comparative X-ray structures of EthR complexed with either clicked ligand BDM14950 or its azide precursor showed ligand-dependent conformational impacts on the protein architecture. This approach revealed two mobile phenylalanine residues that control the access to a previously hidden hydrophobic pocket that can be further exploited for the development of structurally diverse EthR inhibitors. This report shows that protein-directed in situ chemistry allows medicinal chemists to explore the conformational space of a ligand-binding pocket and is thus a valuable tool to guide drug design in the complex path of hit-to-lead processes. © 2010 American Chemical Society.SCOPUS: ar.jinfo:eu-repo/semantics/publishe
ChemInform Abstract: A Convenient Microwave‐Assisted Propylphosphonic Anhydride (T3P®) Mediated One‐Pot Pyrazolone Synthesis.
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