2163-11-3

A selective synthesis of bis(3,5-diketo-1H-pyrazole)-[26]crown- 12 (1, L1) has been performed. Its deprotonation pKa values, and those of the acyclic analogues (3-5) have been measured. The disodium dipyrazolate salt of 1 (2, [L2]2- 2Na+) has been isolated, and mono- and di- nuclear complexes of Zn2+ obtained from 1 ([L1Zn]2+) and 2 ([L2Zn2]2+) have been studied by 13C NMR spectroscopy in DMSO-d6 solution.

We developed three novel positron-emission tomography (PET) probes, 2-tert-butyl-4-chloro-5-{6-[2-(2[18F]fluoroethoxy)-ethoxy]-pyridin-3- ylmethoxy}-2H-pyridazin-3-one ([18F]BCPP-EF), 2-tert-butyl-4-chloro- 5-[6-(4-[18F]fluorobutoxy)-pyridin-3-ylmethoxy]-2H-pyridazin-3-one ([18F]BCPP-BF), and 2-tert-butyl-4-chloro-5-{6-[2-(2-[ 11C]methoxy-ethoxy)-ethoxy]-pyridin-3-ylmethoxy}-2H-pyridazin-3-one ([11C]BCPP-EM), for quantitative imaging of mitochondrial complex 1 (MC-1) activity in vivo. These three PET probes were successfully labeled by nucleophilic [18F]fluorination or by [11C]methylation of their corresponding precursor with sufficient radioactivity yield, good radiochemical purity, and sufficiently high specific radioactivity for PET measurement. The specificity of these probes for binding to MC-1 was assessed with rotenone, a specific MC-1 inhibitor, by a rat brain slice imaging method in vitro. Rat whole-body imaging by small-animal PET demonstrated that all probes showed high uptake levels in the brain as well as in the heart sufficient to image them clearly. The rank order of uptake levels in the brain and the heart just after injection was as follows: high in [18F]BCPP-BF, intermediate in [11C]BCPP-EM, and low in [18F]BCPP-EF. The kinetics of [18F]BCPP-EF and [11C]BCPP-EM provided a reversible binding pattern, whereas [18F]BCPP-BF showed nonreversible accumulation-type kinetics in the brain and heart. Metabolite analyses indicated that these three compounds were rapidly metabolized in the plasma but relatively stable in the rat brain up to 60 min post-injection. The present study demonstrated that [18F]BCPP-EF could be a useful PET probe for quantitative imaging of MC-1 activity in the living brain by PET. Copyright

The design and assembly of new organophosphazene polymeric materials based on supramolecular "host-guest" interactions was accomplished by linkage of supramolecular coupling units to either the main-chain terminus or the side-chains of the parent phosphazene polymer. Noncovalent interactions at the main chain terminus were used to produce amphiphilic palm-Tree like pseudoblock copolymers via host-guest interactions between an adamantane end-functionalized polyphosphazene and a 4-armed β-cyclodextrin (β-CD) initiated poly[poly(ethylene glycol) methyl ether methacylate] branched-star type polymer. Moreover, noncovalent interactions involving polymer side-chains were achieved between polyphosphazenes with β-CD pendant units and other polyphosphazene molecules with adamantyl moieties on the side-chains. These new organo-phosphazene structures based on noncovalent "host-guest" interactions generate new opportunities for the macromolecular modification of polyphosphazenes. The resultant materials demonstrated useful properties including self-aggregation, supramolecular gelation, and stimulus-responsive behavior.

A series of densely grafted star- and comb-shaped molecular brushes composed of polystyrene, poly(tert-butyl acrylate), and poly(N- isopropylacrylamide) were prepared by atom transfer radical polymerization (ATRP) using either cyclotriphosphazenes or polyphosphazenes as initiators. The initiators were prepared by the introduction of a free hydroxyl group into the side chains of a phosphazene cyclic trimer and polymer, followed by esterification with 2-bromopropionyl bromide. The grafting conditions were optimized for various monomers. The kinetics of the reaction were first-order with respect to the monomer concentration in both cyclotriphosphazene and polyphosphazene systems. The molecular weights of the resulting polymers were estimated by gel permeation chromatography (GPC). The side chains of the brush polymers were cleaved from the backbone and analyzed by GPC to confirm the synthesis of well-defined polymer brushes. Brushes based on poly(tert-butyl acrylate) were subjected to hydrolysis to yield negatively charged brushes. In addition, the lower critical solution temperature (LCST) of poly(N- isopropylacrylamide) brush polymers was measured by both dynamic light scattering (DLS) and differential scanning calorimetry (DSC), exhibiting a sharp phase transition at 33 °C. Furthermore, star- and comb-block copolymers with a hard polystyrene core and a soft poly(tert-butyl acrylate) shell were also synthesized.

Provided herein are compounds of Formula A, B or C that can inhibit the replication of influenza viruses, reduce the amount of influenza viruses, and/or treat influenza.

Methods of inhibiting the replication of influenza viruses in a biological sample or patient, of reducing the amount of influenza viruses in a biological sample or patient, and of treating influenza in a patient, comprises administering to said biological sample or patient a safe and effective amount of a compound represented by any of Formulas l-lll, or a pharmaceutically acceptable salt thereof. A pharmaceutical composition comprises a safe and effective amount of such a compound or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, adjuvant or vehicle.

The present invention provides a diagnostic agent for a therapeutic effect on cancer, containing a compound represented by formula (1-0). (In formula (1-0), R represents —O(CH2)n—, —O(CH2)nOC2H4—, —CH2O(CH2)n—, or —CH2O(CH2)nOC2H4—, n represents an integer of 1 to 5, and Q1 represents F or —OCH3.)

The present invention provides, among other things, compounds represented by the general Formula I: (I) and pharmaceutically acceptable salts thereof, wherein L and A (and further substituents) are as defined in classes and subclasses herein and compositions (e.g., pharmaceutical compositions) comprising such compounds, which compounds are useful as inhibitors of hepatitis C virus polymerase, and thus are useful, for example, as medicaments for the treatment of HCV infection.

P-Stereogenic diphosphacrowns containing naphthalene and pyridine rings were synthesized. Facile incorporation of aromatic rings, and chains of different lengths, into the diphosphacrown skeleton was achieved by altering the electrophile in our previously

Novel types of symmetric bis-7-methoxytacrines connected by oligoethyleneoxy chains 3-5 and nonsymmetric monomeric 7-methoxytacrines containing hydroxyl-terminated oligoethyleneoxy chains 6-8 were prepared, and their in vitro/in silico effects on human recombinant AChE (hAChE) and human plasmatic butyrylcholinesterase (hBChE) were compared, with 7-MEOTA (2) as the standard compound. The symmetric bis-7-MEOTA derivatives 3-5 showed hAChE inhibition similar to that of 2. On the other hand, their effects on hBChE revealed an increasing inhibition trend when the oligoethyleneoxy units between the two 7-MEOTA moieties became longer. Accordingly, compounds 4 and 5 showed better selectivity towards hBChE. The most effective in the inhibition hAChE and hBChE was compound 8 with the longest oligoethyleneglycol chain, whereas compounds 6 and 7 resulted in similar IC50 values. A molecular modeling study using substrates 5 and 8 showed a possible binding conformation and protein-ligand interaction between the substrates and AChE/BChE.

Provided is a compound represented by formula (1-0): wherein in formula (1-0), R represents —O(CH2)n—, —O(CH2)nOC2H4—, —CH2O(CH2)n— or —CH2O(CHs

The present invention provides for monodispersed dendrimers having a core, branches and periphery ends, wherein the number of branches increases exponentially from the core to the periphery end and the length of the branches increases exponentially from t

Making defect-free macromolecules is a challenging issue in chemical synthesis. This challenge is especially pronounced in dendrimer synthesis where exponential growth quickly leads to steric congestion. To overcome this difficulty, proportionate branchin

The design, synthesis, and structural characterization, both in solution by 1H NMR and in the solid state by X-ray diffraction on single crystals, of a series of molecular gates based on Sn-porphyrin derivatives are presented. The molecular systemis based on a porphyrin core bearing at the meso positions either phenyl or pyridyl groups as a stator, octahedral Sn(IV) cation located at the center of the porphyrin as a hinge, and different handles connected to the porphyrin through Sn-O axial bonds. The stability of the complexes in the presence of different acids is also reported.

The easily accessible and multi-functionalized 5,8-dimethoxy-6,7-dihydroxy methyl-1,4-dihydro-1,4-methanonaphthalene (1) has been utilized as the basic building material to synthesize the symmetric bis-methanonaphthalene-fused crown ethers 14a-d (BMN-16-crown-4, BMN-22-crown-6, BMN-28-crown-8, and BMN-34-crown-10), that are constructed based on the connection between the α,β-bis-benzylic carbon atoms of diol 1 and oligoethylene glycols (9a-d) via two synthetic routes keyed upon the method of Williamson ether synthesis.