20249-16-5Relevant articles and documents
The exhaustive silylation of 5-nitro-pentan-2-one: Novel processes and opportunities
Tishkov, Alexander A.,Lyapkalo, Il'ya M.,Ioffe, Sema L.,Strelenko, Yuri A.,Tartakovsky, Vladimir A.
, p. 2221 - 2230 (2001)
Treatment of 5-nitro-pentan-2-one (1) with Me3SiOTf/Et3N leads to initial silylation of the C(O)Me-group to give regioisomeric silyl enol ethers 2a and 2b followed by double silylation of the NO2-group furnishing a mixture of N,N-bis(silyloxy)enamine 4a and enoxime TMS ether 6. Employment of a large excess of Me3SiOTf/Et3N triggers a cascade of eliminations and silylations to give a mixture of (E)-4-trimethylsilyloxy-2-trimethylsilyl-pent-2,4-dienenitrile (8) and 3-oxo-1-(1,1,1-trimethylsilyl)-1-cyclobutanecarbonitrile (9). The use of Me3SiCl/DBU changes the selectivity of silylation of 1 to give silyl nitronate 2c.
ISOXAZOLE DERIVATIVES FOR USE IN THE TREATMENT OF PULMONARY DISEASES AND DISORDERS
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Paragraph 0357, (2017/03/21)
The present disclosure features disclosed method of treating disorders such as COPD, bronchitis and/or asthma using disclosed compounds, optionally together with one or more additional active agents. Contemplated methods include administrating orally or by inhalation to a patient one or more disclosed compounds.
Synthesis and Pharmacology of (Pyridin-2-yl)methanol Derivatives as Novel and Selective Transient Receptor Potential Vanilloid 3 Antagonists
Gomtsyan, Arthur,Schmidt, Robert G.,Bayburt, Erol K.,Gfesser, Gregory A.,Voight, Eric A.,Daanen, Jerome F.,Schmidt, Diana L.,Cowart, Marlon D.,Liu, Huaqing,Altenbach, Robert J.,Kort, Michael E.,Clapham, Bruce,Cox, Phil B.,Shrestha, Anurupa,Henry, Rodger,Whittern, David N.,Reilly, Regina M.,Puttfarcken, Pamela S.,Brederson, Jill-Desiree,Song, Ping,Li, Bin,Huang, Susan M.,McDonald, Heath A.,Neelands, Torben R.,McGaraughty, Steve P.,Gauvin, Donna M.,Joshi, Shailen K.,Banfor, Patricia N.,Segreti, Jason A.,Shebley, Mohamad,Faltynek, Connie R.,Dart, Michael J.,Kym, Philip R.
, p. 4926 - 4947 (2016/06/13)
Transient receptor potential vanilloid 3 (TRPV3) is a Ca2+- and Na+-permeable channel with a unique expression pattern. TRPV3 is found in both neuronal and non-neuronal tissues, including dorsal root ganglia, spinal cord, and keratinocytes. Recent studies suggest that TRPV3 may play a role in inflammation, pain sensation, and skin disorders. TRPV3 studies have been challenging, in part due to a lack of research tools such as selective antagonists. Herein, we provide the first detailed report on the development of potent and selective TRPV3 antagonists featuring a pyridinyl methanol moiety. Systematic optimization of pharmacological, physicochemical, and ADME properties of original lead 5a resulted in identification of a novel and selective TRPV3 antagonist 74a, which demonstrated a favorable preclinical profile in two different models of neuropathic pain as well as in a reserpine model of central pain.
