544467-05-2Relevant academic research and scientific papers
INHIBITORS OF HEPATITIS C VIRUS POLYMERASE
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Paragraph 401; 402, (2016/10/11)
The present invention provides, among other things, compounds represented by the general Formula I: (I) and pharmaceutically acceptable salts thereof, wherein L and A (and further substituents) are as defined in classes and subclasses herein and compositions (e.g., pharmaceutical compositions) comprising such compounds, which compounds are useful as inhibitors of hepatitis C virus polymerase, and thus are useful, for example, as medicaments for the treatment of HCV infection.
Competition between azido cleavage and triplet nitrene formation in azidomethylacetophenones
Ranaweera, Ranaweera A. A. Upul,Zhao, Yu,Muthukrishnan, Sivaramakrishnan,Keller, Christopher,Gudmundsdottir, Anna D.
experimental part, p. 1645 - 1655 (2011/09/14)
Photolysis of p- and m-azidomethylacetophenone (1a, 1b) in argon-saturated solutions yields predominantly imine 2a, 2b, whereas irradiation of 1a, 1b in oxygen-saturated solutions results in heterocycles 3a, 3b, aldehydes 4a, 4b and nitriles 5a, 5b. Density functional theory calculations place the energy of the first and second excited state of the triplet ketones (T1K and T 2K) in 1a, 1b in close proximity to each other. The triplet transition state for cleaving the CN bond in 1a, 1b to form azido and benzyl radicals 1aB, 1bB is located only 3 kcal mol-1 (1 kcal = 4.184 kJ) above T1K, indicating that azido cleavage is feasible. The calculations place the energy of the triplet azido group (TA) in 1a, 1b ～25 kcal mol-1 below T1K; thus, this process is also easily accessible via energy transfer. Further, the transition state barrier for TA to expel N2 and form triplet nitrenes is less than 1 kcal mol-1 above TA in 1a, 1b. Laser flash photolysis of 1a, 1b reveals the formation of the triplet excited ketones of 1a, 1b, which decay to form benzyl radicals 1aB, 1bB and triplet alkylnitrenes. The triplet ketones and the benzyl radicals are quenched with molecular oxygen at rates close to diffusion, whereas the triplet nitrenes react more slowly with oxygen (～5 × 105 M-1s-1). We conclude that the triplet alkylnitrenes intercept the benzyl radicals to form 2 in argon-saturated solution, whereas the benzyl radicals are trapped to form 4 in oxygen-saturated solution; thus, the triplet nitrenes react with oxygen to form 3. CSIRO 2010.
Substituted isoxazolines, pharmaceutical compositions containing the same, methods of preparing the same, and uses of the same
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Page/Page column 21, (2008/06/13)
The invention relates to substituted isoxazolines according to the general formula (I) : in which A, R1, R2, R3, R4, Z, X, m, n, and p, are given in the claims, and salts thereof, to pharmaceutical compositions comprising said substituted isoxazolines, to methods of preparing said substituted isoxazolines as well as the use thereof for manufacturing a pharmaceutical composition for the treatment of diseases known to be at least in part mediated by HDAC activity or whose symptoms are known to be alleviated by HDAC inhibitors.
Azido-containing aryl β-diketo acid HIV-1 integrase inhibitors
Zhang, Xuechun,Pais, Godwin C.G.,Svarovskaia, Evguenia S.,Marchand, Christophe,Johnson, Allison A.,Karki, Rajeshri G.,Nicklaus, Marc C.,Pathak, Vinay K.,Pommier, Yves,Burke Jr., Terrence R.
, p. 1215 - 1219 (2007/10/03)
Aryl β-diketo acids (ADK) comprise a general class of potent HIV-1 integrase (IN) inhibitors, which can exhibit selective inhibition of strand transfer reactions in extracellular recombinant IN assays and provide potent antiviral effects in HIV-infected cells. Recent studies have shown that polycyclic aryl or aryl rings bearing aryl-containing substituents are components of potent members of this class. Reported herein is the first use of azido functionality as an aryl replacement in β-diketo acid IN inhibitors. The ability of azido-containing inhibitors to exhibit potent inhibition of IN and antiviral protection in HIV-infected cells, renders the azide group of potential value in the further development of ADK-based IN inhibitors.
