Green photochemistry: photo-Friedel-Crafts acylations of 1,4-naphthoquinone in room temperature ionic liquids

The photo-Friedel-Crafts acylation of 1,4-naphthoquinone with various aldehydes was investigated in a series of room temperature ionic liquids. High conversions and selectivities were achieved in [C(2)mim](+)-based ionic liquids with the highest isolated yields found in [C(2)mim][NTf2]. The developed procedure allowed for a replacement of hazardous solvents such as benzene and acetonitrile which are commonly used for this transformation.

Synthesis and SAR of novel, 4-(phenylsulfamoyl)phenylacetamide mGlu(4) positive allosteric modulators (PAMs) identified by functional high-throughput screening (HTS)

Herein we disclose the synthesis and SAR of a series of 4-(phenylsulfamoyl)phenylacetamide compounds as mGlu(4) positive allosteric modulators (PAMs) that were identified via a functional HTS. An iterative parallel approach to these compounds culminated in the discovery of VU0364439 (11) which represents the most potent (19.8 nM) mGlu(4) PAM reported to date. (C) 2010 Elsevier Ltd. All rights reserved.

The soluble isoform of CTLA-4 as a regulator of T-cell responses

CTLA-4 is a crucial immune regulator that mediates both negative co-stimulation signals to T cells, and regulatory T (Treg) cell extrinsic control of effector responses. Here we present evidence supporting a novel mechanism for this extrinsic suppression, executed by the alternatively spliced soluble CTLA-4 isoform (sCTLA-4). Analyses of human T cells in vitro show that sCTLA-4 secretion can be increased during responses, and has potent inhibitory properties, since isoform-specific blockade of its activity significantly increased antigen-driven proliferation and cytokine (interferon-?, IL-17) secretion. Treg cells were demonstrated to be a prominent source of sCTLA-4, which contributed to suppression in vitro when their numbers were limiting. The soluble isoform was also produced by, and inhibited, murine T cells responding to antigen in vitro, and blockade of its activity in vivo protected against metastatic spread of melanoma in mice. We conclude that sCTLA-4 is an important immune regulator, responsible for at least some of the inhibitory effects previously ascribed to the membrane-bound isoform. These results suggest that the immune system exploits the different CTLA-4 isoforms for either intrinsic or extrinsic regulation of T-cell activity.

European Economic and Social Constitutionalism after the Treaty of Lisbon

European studies frequently regard the economic and social dimensions of EU integration as diametrically opposed, maintaining that this state of affairs is beyond change. This edited collection challenges this perceived wisdom, focusing on the post-Lisbon constitutional landscape. Taking the multi-layered polity that is Europe today as its central organising theme, it examines how the social and the economic might be reconciled under the Union's different forms of governance. The collection has a clear structure, opening with a theoretical appraisal of its theme, before considering three specific policy fields: migration policy and civic integration, company law and corporate social responsibility and the role of third sector providers in public healthcare. It concludes with three case studies in these fields, illustrating how the argument can be practically applied. Insightful and topical, with a unique interdisciplinary perspective, this is an important contribution to European Union law after the Lisbon Treaty

Determination of 3,4-methylenedioxyamphetamine analogues (''ecstasy'') by proton nuclear magnetic resonance spectrometry

A procedure for the determination of three commonly encountered ecstasy type drugs has been demonstrated using proton nuclear magnetic resonance spectrometry (H-1-NMR).

Oxidation of N-(4-methoxybenzyl)-2-pyrrolidinones to N-(4-methoxybenzoyl)-2-pyrrolidinones. Rapid entry to optically active Aniracetam analogues.

Oxidation of readily available N-(4-methoxybenzyl)-5-alkylpyrrolidin-2-ones to the corresponding N-(4-methoxybenzoyl)-5-alkylpyrrolidin-2-ones gives direct access to enantiomerically pure 5-alkyl analogues of the cognition activating agent Aniracetam. Copyright (C) 1996 Elsevier Science Ltd

ASYMMETRIC-SYNTHESIS OF S-(+)-4-AMINO-5-HEXYNOIC ACID

4-Amino-5-hexynoic acid is efficiently synthesised in eight steps (overall yield 10%) from commercially available (S)-glutamic acid. The key step was conversion of an aldehyde to an acetylene using diethylmethydiazophosphonate.

The Shifting Battleground of Article 4(2) TEU: Evolving National Identities and the corresponding need for EU management?

Article 4(2) TEU requires that the European Union (EU) respect the Member States’ national identities, creating a legal obligation enforceable before the CJEU and valuable in political negotiations. However, the concept of national identities is unclear, leaving open questions about the scope or parameters of the provision and its applicability. The CJEU appears likely to take a relatively flexible approach in light of Article 4(2) TEU’s relationship with national constitutional courts’ reserves. This flexible approach would enable Member States to rely upon a range of aspects as part of their national identity, including ones that were previously unidentified. This is a crucial feature if one considers that national identities may evolve gradually or even dramatically, including where Member States purposefully attempt to develop their national identities further. This possibility of an evolved national identity is exemplified by the French Charte de l’Environnement. It may thereby be possible for Member States to stretch the scope and application of Article 4(2) TEU through reference to these evolving national identities. This potential raises significant challenges for the EU regarding the management of Article 4(2) TEU, which it will need to address if it wishes to ensure harmonisation and uniformity in the relevant areas.