The rational engineering of photoresponsive materials, e.g., light-driven molecular motors, is a challenging task. Here, we use structure-related design rules to prepare a prototype molecular rotary ...motor capable of completing an entire revolution using, exclusively, the sequential absorption of two photons; i.e., a photon-only two-stroke motor. The mechanism of rotation is then characterised using a combination of non-adiabatic dynamics simulations and transient absorption spectroscopy measurements. The results show that the rotor moiety rotates axially relative to the stator and produces, within a few picoseconds at ambient T, an intermediate with the same helicity as the starting structure. We discuss how such properties, that include a 0.25 quantum efficiency, can help overcome the operational limitations of the classical overcrowded alkene designs.
Nitrostilbenes characterized by two different or differently substituted aryl moieties can be obtained from the initial ring-opening of 3-nitrobenzo
thiophene with amines. Such versatile building ...blocks couple the well-recognized double electrophilic reactivity of the nitrovinyl moiety (addition to the double bond, followed by, e.g., intramolecular replacement of the nitro group) with the possibility to exploit a conjugated system of double bonds within an electrocyclization process. Herein, nitrostilbenes are reacted with different aromatic enols provided by a double (carbon and oxygen) nucleophilicity, leading to novel, interesting naphthodihydrofurans. From these, as a viable application, aromatization and electrocyclization lead in turn to valuable polycondensed, fully aromatic
-heterocycles.
Selective ligands of the CB2 receptor are receiving considerable attention due to their potential as therapeutic agents for a variety of diseases. Recently, 7-hydroxy-5-oxopyrazolo4,3-
...pyridine-6-carboxamide derivatives were shown to act at the CB2 receptor either as agonists or as inverse agonists/antagonists in vitro and to have anti-osteoarthritic activity in vivo. In this article, we report the synthesis, pharmacological profile, and molecular modeling of a series of twenty-three new 7-hydroxy-5-oxopyrazolo4,3-
pyridine-6-carboxamides with the aim of further developing this new class of selective CB2 ligands. In addition to these compounds, seven other analogs that had been previously synthesized were included in this study to better define the structure-activity relationship (SAR). Ten of the new compounds studied were found to be potent and selective ligands of the CB2 receptor, with
values ranging from 48.46 to 0.45 nM and CB1/CB2 selectivity indices (SI) ranging from >206 to >4739. In particular, compounds
and
were found to be high-affinity CB2 inverse agonists that were not active at all at the CB1 receptor, whereas
acted as an agonist. The functional activity profile of the compounds within this structural class depends mainly on the substitution pattern of the pyrazole ring.
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•Design, synthesis and biological evaluation of novel COX-2 selective inhibitors.•COX-2 inhibitors are efficacious as analgesic agents in vivo.•In silico studies highlight the binding ...mode of the compounds into COX-2 enzyme.
A novel series of 1,5-diarylpyrrol-3-sulfur derivatives (10–12) was synthesized and characterized by NMR and mass spectroscopy and x-ray diffraction. The biological activity of these compounds was evaluated in in vitro and in vivo tests to assess their COX-2 inhibitory activity along with anti-inflammatory and antinociceptive effect.
Results showed that the bioisosteric transformation of previously reported alkoxyethyl ethers (9a-c) into the corresponding alkyl thioethers (10a-c) still leads to selective and active compounds being the COX-2 inhibitory activity for most of them in the low nanomolar range. The oxidation products of 10a,b were also investigated and both couple of sulfoxides (11a,b) and sulfones (12a,b) showed an appreciable COX-2 inhibitory activity. Molecular modeling studies were performed to investigate the binding mode of the representative compounds 10b, 11b, and 12b into COX-2 enzyme and to explore the potential site of metabolism of 10a and 10b due to the different in vivo efficacy. Among the developed compounds, compound 10b showed a significant in vivo anti-inflammatory and antinociceptive activity paving the way to develop novel anti-inflammatory drugs.
Belladine
-oxides active against influenza A virus have been synthetized by a novel laccase-catalyzed 1,4-dioxane-mediated oxidation of aromatic and side-chain modified belladine derivatives. ...Electron paramagnetic resonance (EPR) analysis confirmed the role of 1,4-dioxane as a co-oxidant. The reaction was chemo-selective, showing a high functional-group compatibility. The novel belladine
-oxides were active against influenza A virus, involving the early stage of the virus replication life cycle.
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