Metal-Free Coupling of Saturated Heterocyclic Sulfonylhydrazones with Boronic Acids

The coupling of aromatic moieties with saturated heterocyclic partners is currently an area of significant interest for the pharmaceutical industry. Herein, we present a procedure for the metal-free coupling of 4-, 5-, and 6-membered saturated heterocyclic <i>p</i>-methoxyphenyl (PMP) sulfonylhydrazones with aryl and heteroaromatic boronic acids. This procedure enables a simple, two-step synthesis of a range of functionalized sp²–sp³ linked bicyclic building blocks, including oxetanes, piperidines, and azetidines, from their parent ketones

Novel Amino-pyrazole Ureas with Potent In Vitro and In Vivo Antileishmanial Activity

Visceral leishmaniasis is a severe parasitic disease that is one of the most neglected tropical diseases. Treatment options are limited, and there is an urgent need for new therapeutic agents. Following an HTS campaign and hit optimization, a novel series of amino-pyrazole ureas has been identified with potent in vitro antileishmanial activity. Furthermore, compound <b>26</b> shows high levels of in vivo efficacy (>90%) against Leishmania infantum, thus demonstrating proof of concept for this series

General scheme for addition of different linkers to Hapten 7.

<p>General scheme for addition of different linkers to Hapten 7.</p

Anti-nicotine antibody titer and function in mice.

<p>Panel A: BALB/c mice (n = 12/gp) were immunized by IM injection with 10 µg of different nicotine Hapten-DT conjugates adjuvanted with Al(OH)₃ (40 µg Al³⁺) + CpG 24555 (50 µg) on days 0, 28 and 42. Plasma was collected on day 54 and anti-nicotine antibody levels determined by ELISA (Panel A). On day 56 animals received an IV injection of ³H-nicotine (0.05 mg/kg) and plasma and brains collected. Panel B shows nicotine levels in plasma (ng-eq/mL), and Panel C shows nicotine levels in brain (ng-eq/g).</p

Synthesis of Hapten 5.

<p>Synthesis of Hapten 5.</p

Synthesis of Hapten 9.

<p>Synthesis of Hapten 9.</p

Synthesis of Hapten 10.

<p>Synthesis of Hapten 10.</p

Structures of different linker-modified nicotine hapten.

<p>Structures of different linker-modified nicotine hapten.</p

Synthesis of Hapten 8.

<p>Synthesis of Hapten 8.</p

Nicotine and hapten structures.

<p>The thioacetate of Hapten 8 was deprotected to the thiol for coupling with DT.</p