445026-27-7Relevant academic research and scientific papers
NEW THIADIAZOLE DERIVATIVES
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Page/Page column 79, (2011/04/24)
The present invention relates to thiadiazole derivatives of formula (I), to processes for their preparation and to pharmaceutical compositions containing them. These compounds are potent agonists of S1P1 receptors and thus, they are useful In the treatment, prevention or suppression of diseases and disorders known to be susceptible to improvement by sphingosine-1-phosphate receptors agonists (S1P1), such as autoimmune diseases, chronic immune and inflammatory diseases, transplant rejection, malignant neoplastic diseases, angiogenic-related disorders, pain, neurological diseases, viral and infectious diseases.
CHEMICAL COMPOUNDS
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Page/Page column 31-32, (2008/12/07)
The invention provides compounds Formula (I), their preparation, and their use as pharmaceutically active immunosuppressive agents for the treatment of autoimmune disorders, organ transplant rejection, disorders associated with an activated immune system, as well as other disorders modulated by lymphopenia or SlP receptors.
AGONISTS OF THE SPHINGOSINE- 1- PHOSPHATE RECEPTOR (SLP)
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Page/Page column 82, (2008/06/13)
The invention provides compounds of formula I and formula II, their preparation, a their use as pharmaceutically active immunosuppressive agents for the treatment of autoimmune disorders, organ transplant rejection, disorders associated with an activated immune system, as well as other disorders modulated by lymphopenia or SlP receptors.
CHEMICAL COMPOUNDS
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Page/Page column 94, (2008/06/13)
The invention provides compounds formula I, their preparation, and their use as pharmaceutically active immunosuppressive agents for the treatment of autoimmune disorders, organ transplant rejection, disorders associated with an activated immune system, a
Potent, novel in vitro inhibitors of the Pseudomonas aeruginosa deacetylase LpxC
Kline, Toni,Andersen, Niels H.,Harwood, Eric A.,Bowman, Jason,Malanda, Andre,Endsley, Stephanie,Erwin, Alice L.,Doyle, Michael,Fong, Susan,Harris, Alex L.,Mendelsohn, Brian,Mdluli, Khisimuzi,Raetz, Christian R. H.,Stover, C. Kendall,Witte, Pamela R.,Yabannavar, Asha,Zhu, Shuguang
, p. 3112 - 3129 (2007/10/03)
Deacetylation of uridyldiphospho-3-O-(R-hydroxydecanoyl)-N-acetylglucosamine by LpxC is the first committed step in the Pseudomonas aeruginosa biosynthetic pathway to lipid A; homologous enzymes are found widely among Gram-negative bacteria. As an essential enzyme for which no inhibitors have yet been reported, the P. aeruginosa LpxC represents a highly attractive target for a novel antibacterial drug. We synthesized several focused small-molecule libraries, each composed of a variable aromatic ring, one of four heterocyclic/spacer moieties, and a hydroxamic acid and evaluated the LpxC inhibition of these compounds against purified P. aeruginosa enzyme. To ensure that the in vitro assay would be as physiologically relevant as possible, we synthesized a tritiated form of the specific P. aeruginosa glycolipid substrate and measured directly the enzymatically released acetate. Several of our novel compounds, predominantly those having fluorinated substituents on the aromatic ring and an oxazoline as the heterocyclic moiety, demonstrated in vitro IC50 values less than 1 μM. We now report the synthesis and in vitro evaluation of these P. aeruginosa LpxC inhibitors.
