Nitrostyrene Derivatives of Adenosine 5′-Glutarates Modified with an Alkyl Spacer and their inhibitory activity on epidermal growth factor receptor protein tyrosine kinase

β-Nitrostyrene derivatives of adenosine 5′-glutarates are potent and selective bisubstrate-type inhibitors of the epidermal growth factor receptor protein tyrosine kinase (EGF-R PTK). In an attempt to improve the inhibitory activity, this type of compounds was modified with alkyl spacers of varying length between the nitrostyrene and the glutaryl units. The spacers consisted of 1, 3, 4, and 5 atoms to give compounds of the benzyl, oxyethyl, oxypropyl, and oxybutyl series, respectively (Schemes 1 and 2). Adenosine 5′-esters were prepared in the benzyl and oxypropyl series only. Compared to the compounds in the parent series without spacer (IC₅₀ = 0.7–12 μM ), most of the modified compounds inhibited the EGF-R PTK only marginally or were inactive (IC₅₀ ≥ 100 μM ). The only exceptions were the free acids 19 and 20 with IC₅₀ values of ca. 5 μM . It is noteworthy that esterification of these two hydrogen glutarates with either MeOH or adenosine yielded inactive compounds, which is in contrast to the corresponding substances without spacers.     

Synthesis of Benzazepine Analogues of Noscapine

The synthesis of benzazepine analogues of the opium alkaloid noscapine ( 1 ) is described. The benzazepines 2 and 3 were prepared starting from nornarceine ethyl ester ( 4 ; readily available from 1 ) in several steps. X-Ray analysis of compound 2 revealed that it is not a diastereosisomer mixture but a racemate of the threo-form and thus has the same configuration as 1 .     

Metallo‐supramolecular block copolymer micelles: Improved preparation and characterization

Micelles prepared from amphiphilic block copolymers in which a poly(styrene) segment is connected to a poly(ethylene oxide) block via a bis‐(2,2′:6′,2″‐terpyridine‐ruthenium) complex have been intensely studied. In most cases, the micelle populations were found to be strongly heterogeneous in size because of massive micelle/micelle aggregation. In the study reported in this article we tried to improve the homogeneity of the micelle population. The variant preparation procedure developed, which is described here, was used to prepare two “protomer”‐type micelles: PS₂₀‐[Ru]‐PEO₇₀ and PS₂₀‐[Ru]‐PEO₃₇₅. The dropwise addition of water to a solution of the compounds in dimethylformamide was replaced by the controlled addition of water by a syringe pump. The resulting micelles were characterized by sedimentation velocity and sedimentation equilibrium analyses in an analytical ultracentrifuge and by transmission electron microscopy of negatively stained samples. Sedimentation analysis showed virtually unimodal size distributions, in contrast to the findings on micelles prepared previously. PS₂₀‐[Ru]‐PEO₇₀ micelles were found to have an average molar mass of 318,000 g/mol (corresponding to 53 protomers per micelle, which is distinctly less than after micelle preparation by the standard method) and an average hydrodynamic diameter (d_h) of 18 nm. For PS₂₀‐[Ru]‐PEO₃₇₅ micelles, the corresponding values were M = 603,000 g/mol (31 protomers per micelle) and d_h = 34 nm. The latter particles were found to be identical to the “equilibrium” micelles prepared in pure water. Both micelle types had a very narrow molar mass distribution but a much broader distribution of s values and thus of hydrodynamic diameters. This indicates a conformational heterogeneity that is stable on the time scale of sedimentation velocity analysis. The findings from electron microscopy were in disagreement with those from the sedimentation analysis both in average micelle diameter and in the width of the distributions, apparently because of imperfections in the staining procedure. The preparation procedure described also may be useful in micelle formation from other types of protomers. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 4458–4465, 2004     

The magnetization behavior of nanocrystalline permanent magnets based on the Stoner–Wohlfarth Model

The magnetization behavior in nanocrystalline permanent magnets has been investigated using mean field Stoner–Wohlfarth model. The model is comparatively simple but allows the numerical treatment of extended nanostructures. The predominant intergrain exchange coupling is expressed by a mean field constant N_m in spite of no explicit relationship between N_m and the microstructure. By this model, the experimental phenomena, such as the remanence enhancement, the shape of demagnetization curve, the irreversible magnetization, the exchange bias field and their respective temperature dependence, can be well explained. The N_m dependence of magnetic properties has been extensively discussed in the present paper.     

Level of nodes in increasing trees revisited

Simply generated families of trees are described by the equation T(z) = ϕ(T(z)) for their generating function. If a tree has n nodes, we say that it is increasing if each node has a label ∈ { 1,…,n}, no label occurs twice, and whenever we proceed from the root to a leaf, the labels are increasing. This leads to the concept of simple families of increasing trees. Three such families are especially important: recursive trees, heap ordered trees, and binary increasing trees. They belong to the subclass of very simple families of increasing trees, which can be characterized in 3 different ways. This paper contains results about these families as well as about polynomial families (the function ϕ(u) is just a polynomial). The random variable of interest is the level of the node (labelled) j, in random trees of size n ≥ j. For very simple families, this is independent of n, and the limiting distribution is Gaussian. For polynomial families, we can prove this as well for j,n → ∞ such that n − j is fixed. Additional results are also given. These results follow from the study of certain trivariate generating functions and Hwang's quasi power theorem. They unify and extend earlier results by Devroye, Mahmoud, and others. © 2007 Wiley Periodicals, Inc. Random Struct. Alg., 2007