Studies have demonstrated a positive correlation between inflammation, metastasis, or atherosclerosis and the unbalanced or culminated expression of matrix metalloproteinases (MMPs). The molecular imaging of locally upregulated MMP activity in vivo is a clinical challenge. Actually, radioligands based on nonpeptidyl MMP inhibitors (MMPIs) are currently in development as putative radiopharmaceutical agents for the noninvasive in vivo assessment of activated MMPs. Nonpeptidyl MMPIs bind to the zinc active site of the activated enzyme via mono- (e.g. carboxylate) or bidentate (e.g. hydroxamate) complexation thereby exhibiting a broad-spectrum MMP binding potency. Thus, these mentioned endopeptidase inhibitors should be useable lead compounds for the redevelopment as diagnostic MMPI radiotracers. Recently, the non-hydroxamate C-5-disubstituted pyrimidine-2,4,6-triones were disclosed as subgroup-selective MMP inhibitors. We here describe a set of fine-tuned barbiturates as a new class of MMPI radiotracers for the noninvasive in vivo visualization of activated MMPs using scintigraphic techniques such as SPECT or PET.

A systematic study of the direction of nucleophilic attack of the nucleophiles Me 3 MEMe 2 (M ϭ Si, Sn; E ϭ P, As), NaOMe, LiR (R ϭ Me, nBu, Ph) and PhMgBr on 5,6,7,8-tetrafluoroquinoline (1), 6-CF 3 -5,7,8-trifluoroquinoline (2) and 5,7,8-trifluoroquinoline (3) was performed with the aim to develop synthetic routes to specific functional derivatives and to gain a deeper insight into the mechanisms governing the regioselectivity. With the fairly "soft" nucleophiles Me 3 MEMe 2 in general mixtures of 7-Me 2 EC-(main product) and 6-Me 2 EC-derivatives (side product) are formed (Schemes 1, 2, 4). Sulfuration of the isomer mixtures with E ϭ P yields mixtures of the corresponding thiophosphano derivatives. The observed regioselectivity is explained by a concerted action of two factors: (i) The influence of the heteroatom N on the stabilization of the σ-complex type transition states and (ii) the collective effect of four fluorine substituents favouring 6-and 7-substitution.Ϫ The reaction of 1 with sodium methoxide (Scheme 3) was carried out to test the early conclusion on the exclusive formation of 7methoxy-5,6,8-trifluoroquinoline (14) [2], made on the basis of a GC-analysis. For that purpose the molar ratio 1 : MeO Ϫ was varied from 1 : 1.25 over 1 : 1 to 1 : 0.5. Ϫ In the reactions of the quinoline Regioselektivität von 5,6,7,8-Tetrafluorchinolin und der 6-X-Trifluorchinoline mit X ‫؍‬ CF 3 , H in Reaktionen mit Nucleophilen Inhaltsübersicht. Die Nucleophile Me 3 MEMe 2 (M ϭ Si, Sn; E ϭ P, As), NaOMe, LiR (R ϭ Me, nBu, Ph) und PhMgBr wurden hinsichtlich der Richtung des nucleophilen Angriffs auf 5,6,7,8-Tetrafluorchinolin (1), 6-CF 3 -5,7,8-trifluorchinolin (2) und 5,7,8-trifluorchinolin (3) untersucht mit dem Ziel, Synthesewege zu bestimmten funktionalisierten Derivaten zu entwickeln und einen tieferen Einblick in die Mechanismen der Regioselektivität zu gewinnen. Bei Verwendung der relativ "weichen" Nucleophile Me 3 MEMe 2 werden generell Gemische des 7-Me 2 EC-(Hauptprodukt) und 6-Me 2 EC-Derivats (Nebenprodukt) (Schemes 1, 2, 4) gebildet. Durch Sulfurierung der Isomerenmischungen mit E ϭ P entstehen Gemische der entsprechenden Thiophosphan-Verbindungen. Die beobachtete Regioselektivität wird mit einer konzertierten Aktion zweier Faktoren erklärt: 1) Dem Einfluss des Heteroatoms N auf die Stabilität der möglichen σ-Komplex-Intermediate und 2) der kollektiven Wirkung von vier Fluorsubstituenten, die 6-und 7-Substitution favorisieren. Ϫ Die Umsetzung von 1 mit Natriummethoxid (Scheme 3) wurde durchgeführt, um die früher [2] aus einer GC-Analyse des Reaktionsgemisches gefolgerte ausschließliche 71 precursors 1Ϫ3 with the organometallic reagents LiR (R ϭ Me, nBu, Ph) and PhMgBr (Scheme 5) products of the nucleophileaddition at position 2 were obtained in high yields, which with hydrochloric acid led to 2-R-1,2-dihydro-5,6,7,8-tetrafluoroquinolines. In contact with air or by reaction with MnO 2 , oxidation to aromatic 2-R-5,6,7,8-tetrafluoroquinolines occurred. To rationalize the observed differences between the "sof...

Die Komplexe ABF4, die sich beim Erhitzen nach ABF4,f,fl  AF,f + BF3 (A  LiCs) zersetzen, geben neben BF3 auch A2(BF4)2‐Moleküle (A  K, Rb, Cs) an die Gasphase ab. Auftrittspotentiale wurden bestimmt.

The isotypic carbides Ln4C7 (Ln = Ho, Er, Tm, Lu) were prepared by arc-melting of the elemental components, followed by annealing at 1300 °C. The positions of the metal and of some carbon atoms of the monoclinic crystal structure of LU4C7 were determined from X-ray powder data, and the last carbon positions were found and refined from neutron powder diffraction data: P21/c, a = 360.4(1), b = 1351.4(3), c = 629.0(2) pm, β = 104.97(2)°, Z = 2, R = 0.026 for 429 structure factors and 15 positional parameters. The structure contains isolated carbon atoms with octahedral lutetium coordination and linear C3-units, with C-C bond lengths of 132(1) and 135(1) pm. This carbide may therefore be considered as derived from methane and propadiene. The hydrolysis of LU4C7 with distilled water yields mainly methane and propine, while the hydrolyses of the corresponding holmium and erbium carbides resulted in relatively large amounts of saturated and unsaturated C2-hydrocarbons in addition to the expected products methane and propine. The structure comprises two-dimensionally infinite NaCl-type building elements, which are separated by the C3-units. It may be described as a stacking variant of a previously reported structure of HO4C7, now designated as the a-modification. The Lu4C7-type β -modification was obtained at higher temperatures. Its structure was refined by the Rietveld method from X-ray powder data to a residual R = 0.037 for 320 F values and 15 positional parameters. Lu4C7 is Pauli paramagnetic; β -HO4C7 and Er4C7 show Curie-Weiss behavior with magnetic ordering temperatures of less than 20 K.

Die massenspektroskopische Untersuchung des Systems CuCl,f/Al2Cl6,g ergab, daß nur Cu3Al2Cl8 als wesentliche Gaskomplexe auftreten. Die Ergebnisse von Mitführungsmessungen, die LAUGHLIN und Gregory (1976) veröffentlicht und irrtümlich dem Komplex CuAlCl4zugeordnet haben, lassen sich mit den Gleichgewichten und wiedergeben.Die Komplexe Cu3AlCl6 und Cu2Al2Cl8 haben wahrscheinlich (wie Cu4Cl4) eine Struktur mit würfelähnlichem Gerüst.