Heat shock protein 90 inhibitors. A text book example of medicinal chemistry?: Heat shock protein 90 inhibitors. A text book example of medicinal chemistry?

International audienc

ATPase inhibitors of heat-shock protein 90, second season.

International audienceIn the past four years, the ATP-dependent heat-shock protein 90 has remained the focus of much interest. Phase I and phase II anticancer clinical trials with first-generation inhibitors, although sometimes disappointing, have yet to report a forbidding side-effect inherent to the inhibition of this chaperone, which has a very complex and widespread role in cell biochemistry. Research in the field has started to unravel an elaborate regulation picture leading to the proper folding of many proteins. On the medicinal chemistry side, a second wave of inhibitors has been reported. This review attempts to describe all the ATPase inhibitors of HSP90 reported since our last survey

Preparation and chemistry of 3/5-halogenopyrazoles.

International audienc

Synthetic Accesses to 3/5-pyrazole Carboxylic Acids

International audienceThis review attempts to sum up all the synthetic accesses to 3/5-pyrazole carboxylic acids or esters published, or patented, in the last 120 years. Many of them have demonstrated their robustness as well as quite large scopes. However, a majority are relying on the regioselectivity of reactions such as ketones deprotonations,cyclocondensations or [2+3] cycloadditions. For this reason, the preparation of original 3/5-carboxypyrazoles featuring a structure departing from the inherent regioselectivity of these synthetic accesses could be problematic. Moreover, a large scale synthesis of some 3/5-carboxypyrazoles could be a real challenge. It is thus reasonable to forecast that even more synthetic methodologies should be reported in the future in attempts to meet such requirements

Antituberculosis drugs: ten years of research.: Antituberculosis drugs: ten years of research.

International audienceTuberculosis is today amongst the worldwide health threats. As resistant strains of Mycobacterium tuberculosis have slowly emerged, treatment failure is too often a fact, especially in countries lacking the necessary health care organisation to provide the long and costly treatment adapted to patients. Because of lack of treatment or lack of adapted treatment, at least two million people will die of tuberculosis this year. Due to this concern, this infectious disease was the focus of renewed scientific interest in the last decade. Regimens were optimized and much was learnt on the mechanisms of action of the antituberculosis drugs used. Moreover, the quest for original drugs overcoming some of the problems of current regimens also became the focus of research programmes and many new series of M. tuberculosis growth inhibitors were reported. This review presents the drugs currently used in antituberculosis treatments and the most advanced compounds undergoing clinical trials. We then provide a description of their mechanism of action along with other series of inhibitors known to act on related biochemical targets. This is followed by other inhibitors of M. tuberculosis growth, including recently reported compounds devoid of a reported mechanism of action

Optimized palladium-based approaches to analogues of PK 11195

International audienceThe peripheral-type benzodiazepine receptor ligands such as PK 11195 and Ro 5-4864 were found more than twenty years ago in the course of research on neurobiology. These ligands were instrumental in pointing out an involvement of the peripheral-type benzodiazepine receptor (PBR) in apoptosis processes. With in mind an improvement of the solubility of PK 11195 in biological media, we report here improved reaction conditions for the palladium-based arylation reaction of alkyl 1-bromoisoquinoline-3-carboxylates and its ethyl 4-bromoquinoline-2-carboxylate isomer. The use of [1,1'-bis(diphenylphosphino) ferrocene] dichloropalladium as a precatalyst enabled a much improved preparation of an array of the 1-arylisoquinoline-3-carboxylates as well as 4-arylquinoline-3-carboxylates. This work should pave the way for the design of chemical probes aiming at the elucidation of the PBR biological role(s)

New alkoxypyrazoles

The present invention relates to a process for the preparation of alkoxypyrazoles and new alkoxypyrazole compounds

An Improved Preparation of 3-Alkoxypyrazoles

International audienc

Non-quinolone Inhibitors of Bacterial Type IIA Topoisomerases: A Feat of Bioisosterism

Non-quinolone Inhibitors of Bacterial Type IIA Topoisomerases: A Feat of Bioisosteris