Selective 5-Hydroxytryptamine 2C Receptor Agonists Derived from the Lead Compound Tranylcypromine: Identification of Drugs with Antidepressant-Like Action

We report here the design, synthesis, and pharmacological properties of a series of compounds related to tranylcypromine (9), which itself was discovered as a lead compound in a high-throughput screening campaign. Starting from 9, which shows modest activity as a 5-HT2C agonist, a series of 1-aminomethyl-2-phenylcyclopropanes was investigated as 5-HT2C agonists through iterative structural modifications. Key pharmacophore feature of this new class of ligands is a 2-aminomethyl-trans-cyclopropyl side chain attached to a substituted benzene ring. Among the tested compounds, several were potent and efficacious 5-HT2C receptor agonists with selectivity over both 5-HT2A and 5-HT2B receptors in functional assays. The most promising compound is 37 with 120- and 14-fold selectivity over 5-HT2A and 5-HT2B, respectively (EC50 = 585, 65, and 4.8 nM at the 2A, 2B, and 2C subtypes, respectively). In animal studies, compound 37 (10–60 mg/kg) decreased immobility time in the mouse forced swim test

Enantioselective total synthesis of the antifungal agent (6S)-5,6-dihydro-6-[(2R)-2-hydroxy-6-phenylhexyl]-2H-pyran-2-one

An enantioselective route for the synthesis of (6S)-5,6-dihydro-6-[(2R)-2-hydroxy-6-phenylhexyl]-2H-pyran-2-one is reported. The synthesis is based on epoxide ring opening with a Grignard reagent and stereoselective reduction employing catecholborane as key reactions

Synthesis, characterization and photocatalytic activity studies of tellurium containing defect pyrochlores, MSn_0.5Te_1.5O₆ (M = K, Ag, Cu_0.5 and Sn_0.5)

1174-1181Four new metal tin tellurites, MSn0.5Te1.5O6 (M = K, Ag, Cu0.5 and Sn0.5), have been synthesized by standard solid-state and facile ion exchange reactions and characterized by powder X-ray diffraction, FTIR, SEM-EDS and UV-vis diffuse reflectance spectroscopic techniques. All the compositions crystallize in cubic lattice with Fdmspace group, and are isomorphous with KTi0.5Te1.5O6. The photocatalytic activity of the as prepared materials for methylene blue and methyl violet degradation has been investigated under visible light irradiation. The AgSn0.5Te1.5O6 photocatalyst exhibits higher photocatalytic activity than MSn0.5Te1.5O6 (M = K, Cu0.5 and Sn0.5) for photodegradation of methylene blue and methyl violet. The higher photocatalytic performance of AgSn0.5Te1.5O6 is ascribed to its low band gap energy, which endows it with a very strong photooxidation ability to produce OH● and O2●- radicals as active species. The catalyst stability and mechanism of photocatalysis is also discussed

Stereoselective total synthesis of paecilomycin E and F and its two congeners Cochliomycin C and 6-epi-Cochliomycin C

<p>An efficient and concise approach to the total synthesis of Paecilomycins E (<b>1</b>) and F (<b>2</b>), Cochliomycin C (<b>4</b>) and 6-epi-Cochliomycin C (<b>3</b>) is described. The synthesis involves novel route to the synthesis of Paecilomycin E and F and further conversion to Cochliomycin C and 6-epi-Cochliomycin C. Olefin metathesis and base promoted macro lactonization being the key reactions followed by chlorination to achieve target Cochliomycin C and 6-epi-Cochliomycin C.</p