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1.
Chempluschem ; 82(3): 433-441, 2017 Mar.
Article in English | MEDLINE | ID: mdl-31962017

ABSTRACT

Treatment of ß-naphthil dihydrazone, 1, with silver oxide yields di(ß-naphthyl)acetylene, 2, which undergoes Diels-Alder cycloaddition with tetra(ß-naphthyl)cyclopentadienone, 4, to give hexa(ß-naphthyl)benzene, 5, upon decarbonylation. Molecules 1, 2 and 4 have been characterised by X-ray crystallography, but hexa(ß-naphthyl)benzene exhibits rotational disorder of the peripheral substituents. Nevertheless, calculations at the density functional level reveal the favoured structure of 5 to be a molecular propeller, in which the eight possible rotamers are essentially iso-energetic. Variable-temperature NMR spectroscopy studies yield a naphthyl rotational barrier of approximately 17 kcal mol-1 , similar to that previously found for meta-substituted phenyl groups. Enantiomerisation of hexa(ß-naphthyl)benzene engendered by rotation of a single naphthyl ring has been studied by DFT calculations, and the process has been represented pictorially.

2.
Dalton Trans ; 41(12): 3523-35, 2012 Mar 28.
Article in English | MEDLINE | ID: mdl-22301566

ABSTRACT

Reaction of [PtCl(2)(COD)] and [PtI(2)(COD)] with 2,7-di-tert-butyl-5-diphenylboryl-4-diphenylphosphino-9,9-dimethylthioxanthene (TXPB) afforded square planar [PtCl(2)(TXPB)] (1B) and [PtI(2)(TXPB)] (4B), both of which were crystallographically characterized. Single-crystal X-ray quality crystals were also obtained for [PdCl(2)(TXPB)] (2B; Emslie et al., Organometallics, 2008, 27, 5317) as 2B·2CH(2)Cl(2) and solvent-free 2B. Both the chloro and iodo TXPB complexes exhibit metal-halide-borane bridging interactions similar to those in previously reported [RhCl(CO)(TXPB)] (3B) and [RhI(CO)(TXPB)] (5B) (Emslie et al., Organometallics, 2006, 25, 583 and Inorg. Chem., 2010, 49, 4060). To facilitate a more detailed analysis of M-X-BR(3) (X = Cl and I) interactions, a borane-free analogue of the TXPB ligand, 2,7-di-tert-butyl-4-diphenylphosphino-9,9-dimethylthioxanthene (TXPH), was prepared. Reaction with [PtX(2)(COD)] (X = Cl or I), [PdCl(2)(COD)] and 0.5 [{RhCl(CO)(2)}(2)] provided square planar [PtCl(2)(TXPH)] (1H), [PdCl(2)(TXPH)] (2H), [RhCl(CO)(TXPH)] (3H) and [PtI(2)(TXPH)] (4H). M-Cl-BR(3) and M-I-BR(3) bonding in 1B-5B was then probed through the use of structural comparisons, IR and NMR spectroscopy, cyclic voltammetry, and DFT calculations (Slater-type orbitals, Mayer bond orders, Hirshfeld charges, fragment analysis, SCF deformation density isosurfaces, and energy decomposition analysis).

3.
Chem Commun (Camb) ; 47(26): 7518-20, 2011 Jul 14.
Article in English | MEDLINE | ID: mdl-21625674

ABSTRACT

A new approach for preparing (99m)Tc-labelled compounds in high effective specific activity was developed by utilizing a novel fluorous ligand capture (FLC) agent and a chemoselective filtration strategy. This paradigm eliminates the need to use HPLC to obtain technetium(I) based molecular imaging probes free from residual precursor.


Subject(s)
Chemical Fractionation/methods , Organotechnetium Compounds/chemistry , Organotechnetium Compounds/isolation & purification , Chromatography, High Pressure Liquid , Ligands , Solutions , Substrate Specificity
4.
Acta Crystallogr Sect E Struct Rep Online ; 64(Pt 2): o463, 2008 Jan 16.
Article in English | MEDLINE | ID: mdl-21201489

ABSTRACT

The title compound, C(16)H(12)N(2)O(2)S, was prepared by a Neigishi cross-coupling reaction to investigate the coordination chemistry of thio-phene-containing ligands. In the mol-ecule, the pyridine rings are twisted from the thio-phene ring by 20.6 (1) and 4.1 (2)°. The six-membered dihydro-dioxine ring is in a half-chair conformation.

5.
Acta Crystallogr Sect E Struct Rep Online ; 64(Pt 4): o719, 2008 Mar 14.
Article in English | MEDLINE | ID: mdl-21202109

ABSTRACT

The title compound, C(11)H(9)N(3)OS, was prepared to investigate the coordination chemistry of thio-phene-containing ligands as precursors to inter-esting metallopolymers. The mol-ecule is nearly planar. The angle between the thio-phene and pyridine rings is 8.63 (4)° and features the expected trans configuration about the imine bond. The structure is stabilized by a weak inter-molecular N-H⋯O hydrogen bond. The distance between centroids of adjacent thio-phene rings [3.67 (8) Å] suggests the presence of π-π inter-actions.

6.
Mol Cancer Ther ; 6(7): 2012-21, 2007 Jul.
Article in English | MEDLINE | ID: mdl-17620431

ABSTRACT

With the development of targeted therapeutics, especially for small-molecule inhibitors, it is important to understand whether the observed in vivo efficacy correlates with the modulation of desired/intended target in vivo. We have developed a small-molecule inhibitor of all three vascular endothelial growth factor (VEGF) receptors (VEGFR), platelet-derived growth factor receptor, and c-Kit tyrosine kinases, pazopanib (GW786034), which selectively inhibits VEGF-induced endothelial cell proliferation. It has good oral exposure and inhibits angiogenesis and tumor growth in mice. Because bolus administration of the compound results in large differences in C(max) and C(trough), we investigated the effect of continuous infusion of a VEGFR inhibitor on tumor growth and angiogenesis. GW771806, which has similar enzyme and cellular profiles to GW786034, was used for these studies due to higher solubility requirements for infusion studies. Comparing the pharmacokinetics by two different routes of administration (bolus p.o. dosing and continuous infusion), we showed that the antitumor and antiangiogenic activity of VEGFR inhibitors is dependent on steady-state concentration of the compound above a threshold. The steady-state concentration required for these effects is consistent with the concentration required for the inhibition of VEGF-induced VEGFR2 phosphorylation in mouse lungs. Furthermore, the steady-state concentration of pazopanib determined from preclinical activity showed a strong correlation with the pharmacodynamic effects and antitumor activity in the phase I clinical trial.


Subject(s)
Antineoplastic Agents/pharmacology , Antineoplastic Agents/pharmacokinetics , Indazoles/pharmacology , Indazoles/pharmacokinetics , Neovascularization, Pathologic/pathology , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/pharmacokinetics , Pyrimidines/pharmacology , Pyrimidines/pharmacokinetics , Sulfonamides/pharmacology , Sulfonamides/pharmacokinetics , Sulfones/pharmacology , Sulfones/pharmacokinetics , Animals , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/blood , Cell Line, Tumor , Cell-Free System , Cornea/pathology , Dose-Response Relationship, Drug , Female , Fibroblast Growth Factor 2/pharmacology , Humans , Indazoles/administration & dosage , Indazoles/blood , Inhibitory Concentration 50 , Mice , Mice, Nude , Phosphorylation/drug effects , Phosphotyrosine/metabolism , Protein Kinase Inhibitors/administration & dosage , Protein Kinase Inhibitors/blood , Pyrimidines/administration & dosage , Pyrimidines/blood , Receptors, Vascular Endothelial Growth Factor/antagonists & inhibitors , Sulfonamides/administration & dosage , Sulfonamides/blood , Sulfones/administration & dosage , Sulfones/blood , Vascular Endothelial Growth Factor A/pharmacology
7.
Inorg Chem ; 45(15): 5727-9, 2006 Jul 24.
Article in English | MEDLINE | ID: mdl-16841972

ABSTRACT

Microwave heating was used to prepare eta5-rhenium carborane complexes in aqueous reaction media. For carboranes bearing sterically demanding substituents, isomerization of the cage from 3,1,2 to 2,1,8 derivatives occurred concomitantly with complexation. Microwave heating was equally effective at the tracer level using technetium-99m, affording access to a new class of synthons for designing novel molecular imaging agents.


Subject(s)
Carbon/chemistry , Chemistry/methods , Microwaves , Organotechnetium Compounds/chemical synthesis , Radiopharmaceuticals/chemical synthesis , Rhenium/chemistry , Technetium/chemistry , Metals/chemistry , Models, Chemical , Molecular Conformation , Organotechnetium Compounds/chemistry , Radiopharmaceuticals/chemistry
8.
Chemistry ; 12(12): 3275-86, 2006 Apr 12.
Article in English | MEDLINE | ID: mdl-16470883

ABSTRACT

1-Phenyl-3,3-biphenyleneallene (2), the base-catalyzed rearrangement product of 9-phenylethynylfluorene (1) yields a yellow, head-to-tail dimer 6 that, upon gentle warming, is converted to the red tail-to-tail isomer trans-3,4-diphenyl-1,2-bis(fluorenylidene)cyclobutane (7), in which the two fluorenylidene moieties severely overlap. The helical sense of the fluorenylidene moieties in 7 matches that of the phenyl substituents, and the interplanar angle between the fluorenylidene moieties is 41 degrees . At 80 degrees C, 6 isomerizes to orange cis-3,4-diphenyl-1,2-bis(fluorenylidene)cyclobutane (8), which at 110 degrees C is converted to orange trans diastereomer 9, whereby the helicity of the overlapping fluorenylidene moieties is reversed from that in 7 such that they are aligned with the ring hydrogen atoms, and the interplanar angle between the fluorenylidene moieties is now 60 degrees . At 180 degrees C, 6 rearranges to dispirodihydrotetracene 3 and blue, electroluminescent diindenotetracene 4, which is readily oxidized to peroxide 5. In the solid state, both 3 and 4 adopt structures with Ci symmetry (only an inversion center) such that the central polycyclic framework is nonplanar. Deprotonation of yellow head-to-tail allene dimer 6 with tBuOK in DMSO and reprotonation with HOAc yields the [1,3]-hydrogen migration product 10, in which the proton originally on the cyclobutane ring is now sited at C9 on the exocyclic fluorenyl substituent. Analogously, deprotonation and reprotonation of orange dimer 9 furnishes [1,3]-hydrogen migration product 11. Side product 17, formed during the synthesis of 1 from 9-phenylethynylfluoren-9-ol, BF3 and Et3SiH, was shown to be a silyl-indene spiro-linked to C9 of fluorene. All products were characterized by NMR spectroscopy and X-ray crystallography, and the mechanisms of these interconversions are discussed.

9.
Org Lett ; 6(5): 787-90, 2004 Mar 04.
Article in English | MEDLINE | ID: mdl-14986975

ABSTRACT

The attempted Diels-Alder reaction between 9-phenylethynylfluorene and tetracyclone yields instead three products resulting from the dimerization of the isomeric allene. The major product is 8,16-diphenyl-diindeno[1,2,3-de:1',2',3'-mn]naphthacene, in which each terminal ring is derived from a fluorenyl unit; aerial oxidation then yields a peroxide. A dihydronaphthacene bearing fluorenyl moieties spiro-bonded at the C(5) and C(11) positions was also identified. The structures of the naphthacenes were elucidated by X-ray crystallography, and a mechanistic rationale is offered. [reaction: see text]

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