Identification of potent, soluble, and orally active TRPV1 antagonists

Synthesis of 3,4,5‐Trisubstituted Isoxazoles from Morita–Baylis–Hillman Acetates by an NaNO2/I2‐Mediated Domino Reaction

“…Isoxazoles,aprivileged class of five-member nitrogen heterocycles,occupy an important place in organic chemistry because of their wide applications in pharmaceuticals,b iologically active molecules,advanced organic materials,and as intermediates in organic synthesis. [1][2][3][4][5] Owing to this ubiquity, their preparation has received remarkable attention and there are already scores of elegant methods which are general, regioselective,a nd high yielding. [6] As summarized by Carreira et al, [6m] the classical routes to isoxazole derivatives involve condensations with hydroxylamine,c yclization of ketoxime dianions,a nd propargylic oximes,a sw ell as 1,3dipolar cycloaddition reactions.Unfortunately,these methods were inefficient for the synthesis of 3-nitroisoxazoles,w hich are potent antimicrobials.…”

Medicinal Chemistry, Pharmacology, and Clinical Implications of TRPV1 Receptor Antagonists

“…In this series, the 4‐ iso butylmethylamino derivative 57 (pIC 50 = 9; Fig. ) demonstrated improved oral bioavailability (33%) as compared to compound 54 , demonstrating significant attenuation of the acute inflammatory thermal response in the rat capsaicin Hargreaves assay ( p < 0.01) …”

Three-Component Reactions of Alkynone o-Methyloximes, Element Selenium, and Boronic Acids Leading to 4-Organoselenylisoxazoles

“…Furthermore, 1a could react with diphenyldiselenide to provide the desired product in 95% yield (Scheme 2c). [1,1′-Biphenyl]-4-ol (6) and alcohol (8) could be isolated when substrate 5 or 7 was subjected to the standard conditions (Scheme 2d,e).…”

“…Isoxazoles 1 represent an important class of heterocycles, as their derivatives are shown to exhibit a wide range of promising pharmaceutical properties including anti-inflammatory, 2 antimicrobial, 3 anticancer, 4 COX-2 inhibitory, 5 and antinociceptive activity. 6 On the other hand, selenium is also a useful element in biologically active molecules, functional materials, synthetic intermediates, and organic catalysts. 7 Incorporation of the selenium atom into a heterocyclic skeleton can pose a certain degree of influence on physicochemical and biological properties as well as the reactivity.…”