Furo[2,3‐d]pyrimidines and Oxazolo[5,4‐d]pyrimidines as Inhibitors of Receptor Tyrosine Kinases (RTK)

Receptor tyrosine kinases such as VEGFR2 (vascular endothelial growth factor receptor 2, KDR) or EGFR (epidermal growth factor receptor) play crucial roles in a variety of diseases, such as cancer. Recently, some pyrrolopyrimidines were shown to be potent EGFR inhibitors. Therefore, new types of oxazolo[5,4‐d]pyrimidines and furo[2,3‐d]pyrimidines were synthesized (Schemes 1 and 2). Appropriately substituted derivatives of these classes of compounds inhibited VEGFR2 and EGFR with IC₅₀ values in the low nanomolar range (see Table). Generally, the furopyrimidines were somewhat more active than the oxazolopyrimidines. The best inhibitors, 20m, 20p , and 20r , had an IC₅₀ of 3 nM towards EGFR and showed a good selectivity, being distinctly less active towards VEGFR2.     

Hamiltonian dynamics on convex symplectic manifolds

We study the dynamics of Hamiltonian diffeomorphisms on convex symplectic manifolds. To this end we first establish an explicit isomorphism between the Floer homology and the Morse homology of such a manifold, and then use this isomorphism to construct a biinvariant metric on the group of compactly supported Hamiltonian diffeomorphisms analogous to the metrics constructed by Viterbo, Schwarz and Oh. These tools are then applied to prove and reprove results in Hamiltonian dynamics. Our applications comprise a uniform lower estimate for the slow entropy of a compactly supported Hamiltonian diffeomorphism, the existence of infinitely many non-trivial periodic points of a compactly supported Hamiltonian diffeomorphism of a subcritical Stein manifold, new cases of the Weinstein conjecture, and, most noteworthy, new existence results for closed trajectories of a charge in a magnetic field on almost all small energy levels. We shall also obtain some new Lagrangian intersection results. Partially supported by the Swiss National Foundation. Supported by the Swiss National Foundation and the von Roll Research Foundation.     

Structural characterization of radiation‐grafted block copolymer films,using SANS technique

We report small‐angle neutron scattering studies of grafted copolymer films of perfluorinated poly(ethylene propylene), FEP, base polymer and polystyrene, PS, grafted blocks. The films show highly anisotropic scattering patterns, revealing nematic‐like ordering of the crystalline domain structure as a consequence of the processing conditions. Upon grafting, the styrene swells the amorphous domains in the copolymer formation. For styrene content beyond roughly 15%, the amorphous regimes increase on the cost of crystalline domains. To stabilize the rather well‐defined domain structure already given by the original FEP base material, the samples need to be cross‐linked. Without cross‐linking, the nanometer length scale domains vanish, and some large scale structure takes over, likely driven by the immiscibility between FEP and PS. © 2008 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 46: 1660–1668, 2008     

A structural investigation of the antibiotic rubiflavin. Preliminary communication

Rubiflavin is shown to be a mixture of antibiotics. The main components have been named rubiflavin A (3) and rubiflavin B (2) and are identified by NMR. spectroscopy as desacetylpluramycin A and kidamycin, respectively.     

KCd2[N(CN)2]5(H2O)4: an enmeshed honeycomb grid

The title compound, poly[potassium [diaquapenta‐μ₂‐dicyanamido‐dicadmium(II)] dihydrate], {K[Cd₂(C₂N₃)₅(H₂O)₂]·2H₂O}_n, contains two‐dimensional anionic sheets of {[Cd₂{N(CN)₂}(H₂O)₂]⁻}_n with a modified (6,3)‐net (layer group , No. 35). Two sets of equivalent sheets interpenetrate orthogonally to form a tetragonal enmeshed grid.     

Synthese von Triafulven-Vorstufen aus trisubstituierten Cyclopropanen

Synthesis of Triafulvene-Precursors from Trisubstituted Cyclopropanes Trisubstituted cyclopropanes 5a–f are prepared by carbene addition to the appropriate olefins. While 5a (Y = OAc) and 5c (Y = Cl) rearrange in the presence of BuLi, 5d (Y = SPh) is stable enough to allow the envisaged sequence for triafulvene (Scheme 2) : halogen-Li exchange, followed by methylation of 6d , gives 7d in a 93% yield; after base-induced elimination of HB r from 7d , the key precursor 1-methylene-2-(phenylthio)cyclopropane ( 9 , 70% yield) is isolated. Compound 9 is transformed into the corresponding sulfoxide 10 (83%), sulfone 11 (80%), and sulfonium fluoroborate 12 (95% yield) by subsequent oxidation and methylation, respectively. Some ¹H-NMR results of cyclopropanes 5a–f and 7d as well as of methylidene-cyclopropanes 9–11 are discussed.     

Isolation and Structure of a New Antibiotic Related to Rubiflavin A

A novel antibiotic, PD 121,222, was isolated from a complex of pluramycin-like compounds containing mostly kidamycin and neopluramycin. Spectral analyses showed that this compound is the 14,16-dihydroxy analog of rubiflavin A.     

Triplet-triplet absorption spectra of quinoline and isoquinoline

The difference between the singlet-singlet and the triplet-triplet absorption spectra of quinoline and isoquinoline has been measured from 45 000 to 15 000 cm^?1, in a rigid hydrocarbon glass at 77 K, using a newly constructed computer controlled spectrograph. Both molecules show strong new triplet-triplet absorption bands in the ultraviolet region. Similar bands have recently been found in naphthalene and were assigned to transitions from the lowest triplet state to a triplet state which is doubly excited with respect to the closed shell ground state.