1. Conversion of substituted 5-aryloxypyrazolecarbaldehydes into reduced 3,4'-bipyrazoles: synthesis and characterization, and the structures of four precursors and two products, and their supramolecular assembly in zero, one and two dimensions
Haruvegowda Kiran Kumar, Hemmige S Yathirajan, Nagaraj Manju, Balakrishna Kalluraya, Ravindranath S Rathore, Christopher Glidewell Acta Crystallogr C Struct Chem. 2019 Jun 1;75(Pt 6):768-776. doi: 10.1107/S2053229619006752. Epub 2019 May 23.
The reaction of 5-chloro-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde with phenols under basic conditions yields the corresponding 5-aryloxy derivatives; the subsequent reaction of these carbaldehydes with substituted acetophenones yields the corresponding chalcones, which in turn undergo cyclocondensation reactions with hydrazine in the presence of acetic acid to form N-acetylated reduced bipyrazoles. Structures are reported for three 5-aryloxycarbaldehydes and the 5-piperidino analogue, and for two reduced bipyrazole products. 5-(2-Chlorophenoxy)-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde, C17H13ClN2O2, (II), which crystallizes with Z' = 2 in the space group P-1, exhibits orientational disorder of the carbaldehyde group in each of the two independent molecules. Each of 3-methyl-5-(4-nitrophenoxy)-1-phenyl-1H-pyrazole-4-carbaldehyde, C17H13N3O4, (IV), 3-methyl-5-(naphthalen-2-yloxy)-1-phenyl-1H-pyrazole-4-carbaldehyde, C21H16N2O2, (V), and 3-methyl-1-phenyl-5-(piperidin-1-yl)-1H-pyrazole-4-carbaldehyde, C16H19N3O, (VI), (3RS)-2-acetyl-5-(4-azidophenyl)-5'-(2-chlorophenoxy)-3'-methyl-1'-phenyl-3,4-dihydro-1'H,2H-[3,4'-bipyrazole] C27H22ClN7O2, (IX) and (3RS)-2-acetyl-5-(4-azidophenyl)-3'-methyl-5'-(naphthalen-2-yloxy)-1'-phenyl-3,4-dihydro-1'H,2H-[3,4'-bipyrazole] C31H25N7O2, (X), has Z' = 1, and each is fully ordered. The new compounds have all been fully characterized by analysis, namely IR spectroscopy, 1H and 13C NMR spectroscopy, and mass spectrometry. In each of (II), (V) and (IX), the molecules are linked into ribbons, generated respectively by combinations of C-H...N, C-H...π and C-Cl...π interactions in (II), C-H...O and C-H...π hydrogen bonds in (V), and C-H...N and C-H...O hydrogen bonds in (IX). The molecules of compounds (IV) and (IX) are both linked into sheets, by multiple C-H...O and C-H...π hydrogen bonds in (IV), and by two C-H...π hydrogen bonds in (IX). A single C-H...N hydrogen bond links the molecules of (X) into centrosymmetric dimers. Comparisons are made with the structures of some related compounds.
2. Synthesis and biological study of a flavone acetic acid analogue containing an azido reporting group designed as a multifunctional binding site probe
Krishnan Malolanarasimhan, Christopher C Lai, James A Kelley, Lynn Iaccarino, Della Reynolds, Howard A Young, Victor E Marquez Bioorg Med Chem. 2005 Apr 15;13(8):2717-22. doi: 10.1016/j.bmc.2005.02.035.
Flavone-8-acetic acid (FAA) is a potent immunomodulatory small molecule that is uniquely characterized as being active on mouse but not human cells. Although FAA is a potent inducer of murine cytokine, chemokine and interferon gene expression, its mode of action remains unknown. In this report, we describe the synthesis of a new flavone acetic acid (FAA) analogue, (2-[2-(4-azidophenyl)-4-oxochromen-8-yl-]acetic acid (compound 2). We demonstrate that compound 2 is equally active as the parent FAA in inducing chemokine gene expression and that the azide functional group is capable of reacting with a reporter molecule, such as the FLAG peptide-phosphine, under mild conditions. This reaction will be useful for detecting the drug-bound protein active complex utilizing an anti-FLAG antibody.
3. Identification of a factor IX/IXa binding protein on the endothelial cell surface
S Rimon, R Melamed, N Savion, T Scott, P P Nawroth, D M Stern J Biol Chem. 1987 May 5;262(13):6023-31.
Endothelium provides a specific binding site for Factor IX/IXa which can propagate activation of coagulation by promoting Factor IXa-VIII-mediated activation of Factor X. In this report the endothelial cell Factor IX/IXa binding site has been identified and the coagulant function of the receptor blocked. Studies using [3H]Factor IX derivatized with the photoaffinity labeling agent N-succinimidyl-6-(4'-azido-2'-nitrophenylamino)hexanoate (SANPAH) and cultured bovine endothelial cells demonstrated cross-linking to a trypsin-sensitive cell surface protein of Mr approximately equal to 140,000. Immunoprecipitation of metabolically labeled endothelium with Factor IX derivatized with the cleavable cross-linking agent N-succinimidyl(4-azidophenyl)-1,3'-dithiopropionate and antibody to Factor IX demonstrated the endothelial cell origin of the Mr 140,000 cell surface protein. Blockade of the Factor IX/IXa binding protein by covalently linking SANPAH-5-dimethylaminonaphthalene-1-sulfonyl-Glu-Gly-Arg-Factor IXa or SANPAH-Factor IX prevented both specific Factor IXa binding and effective Factor IXa-VIII-mediated activation of Factor X on endothelium. Following extraction of endothelium with detergents, Factor IX/IXa binding activity was solubilized and could be assayed using a polyvinyl chloride plate binding assay. Western blots of cell extracts demonstrated binding of 125I-Factor IX at Mr approximately equal to 140,000 which was blocked by excess Factor IX, but not antisera to Factor VIII, von Willebrand factor, alpha 2-macroglobulin, or epidermal growth factor receptor. These data indicate that endothelium provides a distinct binding site for Factor IX/IXa consisting, at least in part, of a membrane protein which can modulate the coagulant activity of Factor IXa on the cell surface.
