Synthesis of Heterocyclic Analogs of α‐aminoadipic Acid and its Esters Based on Imidazo[2,1‐b][1,3]Thiazole

A method for the preparation of heterocyclic analogs of α‐aminoadipic acid and its esters based on the imidazo[2,1‐b][1,3]thiazole ring system was developed. In this method, free‐radical bromination of ethyl 6‐methylimidazo[2,1‐b][1,3]thiazole‐5‐carboxylate with NBS afforded a versatile building block, ethyl 6‐bromomethylimidazo[2,1‐b][1,3]thiazole‐5‐carboxylate. Coupling of ethyl 6‐bromomethylimidazo[2,1‐b][1,3]thiazole‐5‐carboxylate with Schöllkopf's chiral auxiliary followed by acidic hydrolysis generated ethyl 6‐[(2S)‐2‐amino‐3‐methoxy‐3‐oxopropyl]imidazo[2,1‐b][1,3]thiazole‐5‐carboxylate. A similar procedure using diethyl (Boc‐amino)malonate yielded racemic 2‐amino‐3‐[(5‐ethoxycarbonyl)imidazo[2,1‐b][1,3]thiazol‐6‐yl]propanoic acid.     

Fragment‐Based De Novo Design Reveals a Small‐Molecule Inhibitor of Helicobacter Pylori HtrA

Sustained identification of innovative chemical entities is key for the success of chemical biology and drug discovery. We report the fragment‐based, computer‐assisted de novo design of a small molecule inhibiting Helicobacter pylori HtrA protease. Molecular binding of the designed compound to HtrA was confirmed through biophysical methods, supporting its functional activity in vitro. Hit expansion led to the identification of the currently best‐in‐class HtrA inhibitor. The results obtained reinforce the validity of ligand‐based de novo design and binding‐kinetics‐guided optimization for the efficient discovery of pioneering lead structures and prototyping drug‐like chemical probes with tailored bioactivity.     

Recent advances in oxidation catalysis using ionic liquids as solvents

Ionic liquids are an interesting alternative to classical solvents presenting several advantages. A variety of catalysts show good or even enhanced activities when applied in ionic liquids. Oxidation catalysis represents a large segment of industrial chemistry, providing both bulk chemicals and intermediates for high value added special products and pharmaceuticals. Particularly for the latter products organometallic and inorganic catalysts are being developed that can be applied in systems consisting of or containing ionic liquids. This work provides an overview on recent developments in this field.     

A new approach to the incorporation of servo constraints in multibody dynamics

A new index reduction approach is developed to solve the servo constraint problems [2] in the inverse dynamics simulation of underactuated mechanical systems. The servo constraint problem of underactuated systems is governed by differential algebraic equations (DAEs) with high index. The underlying equations of motion contain both holonomic constraints and servo constraints in which desired outputs (specified in time) are described in terms of state variables. The realization of servo constraints with the use of control forces can range from orthogonal to tangential [3]. Since the (differentiation) index of the DAEs is often higher than three for underactuated systems, in which the number of degrees of freedom is greater than the control outputs/inputs, we propose a new index reduction method [1] which makes possible the stable numerical integration of the DAEs. We apply the proposed method to differentially flat systems, such as cranes [1,4,5], and non-flat underactuated systems. (© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)     

Epothilone Analogues with Benzimidazole and Quinoline Side Chains: Chemical Synthesis,Antiproliferative Activity,and Interactions with Tubulin

A series of epothilone B and D analogues bearing isomeric quinoline or functionalized benzimidazole side chains has been prepared by chemical synthesis in a highly convergent manner. All analogues have been found to interact with the tubulin/microtubule system and to inhibit human cancer cell proliferation in vitro, albeit with different potencies (IC₅₀ values between 1 and 150 nM ). The affinity of quinoline‐based epothilone B and D analogues for stabilized microtubules clearly depends on the position of the N‐atom in the quinoline system, while the induction of tubulin polymerization in vitro appears to be less sensitive to N‐positioning. The potent inhibition of human cancer cell growth by epothilone analogues bearing functionalized benzimidazole side chains suggests that these systems might be conjugated with tumor‐targeting moieties to form tumor‐targeted prodrugs.     

Importance sampling of rare events in chaotic systems

The European Physical Journal B - A way to make financial models effective is by letting them to represent the so called “fat tails”, i.e., extreme changes in stock prices that are...