40604-49-7Relevant articles and documents
SELECTIVE NON-CYCLIC NUCLEOTIDE ACTIVATORS FOR THE CAMP SENSOR EPAC1
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Page/Page column 00165; 00166; 00198; 00217, (2021/09/26)
The invention relates generally to novel EPAC1 activators, such as Formula (I) and (II) and the preparation thereof as well as the use of EPAC1 activators disclosed herein as to selectively activate EPAC1 in cells.
GLYCOLATE OXIDASE INHIBITORS FOR THE TREATMENT OF DISEASE
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, (2021/01/22)
Described herein are compounds, methods of making such compounds, pharmaceutical compositions and medicaments containing such compounds, and methods of using such compounds to treat or prevent diseases or disorders associated with a defect in glyoxylate metabolism, for example a disease or disorder associated with the enzyme glycolate oxidase (GO) or alterations in oxalate metabolism. Such diseases or disorders include, for example, disorders of glyoxylate metabolism, including primary hyperoxaluria, that are associated with production of excessive amounts of oxalate.
Synthesis and Biochemical Evaluation of Noncyclic Nucleotide Exchange Proteins Directly Activated by cAMP 1 (EPAC1) Regulators
Wang, Pingyuan,Luchowska-Stańska, Urszula,Van Basten, Boy,Chen, Haiying,Liu, Zhiqing,Wiejak, Jolanta,Whelan, Padraic,Morgan, David,Lochhead, Emma,Barker, Graeme,Rehmann, Holger,Yarwood, Stephen J.,Zhou, Jia
, p. 5159 - 5184 (2020/06/03)
Exchange proteins directly activated by cAMP (EPAC) play a central role in various biological functions, and activation of the EPAC1 protein has shown potential benefits for the treatment of various human diseases. Herein, we report the synthesis and biochemical evaluation of a series of noncyclic nucleotide EPAC1 activators. Several potent EPAC1 binders were identified including 25g, 25q, 25n, 25u, 25e, and 25f, which promote EPAC1 guanine nucleotide exchange factor activity in vitro. These agonists can also activate EPAC1 protein in cells, where they exhibit excellent selectivity toward EPAC over protein kinase A and G protein-coupled receptors. Moreover, 25e, 25f, 25n, and 25u exhibited improved selectivity toward activation of EPAC1 over EPAC2 in cells. Of these, 25u was found to robustly inhibit IL-6-activated signal transducer and activator of transcription 3 (STAT3) and subsequent induction of the pro-inflammatory vascular cell adhesion molecule 1 (VCAM1) cell-adhesion protein. These novel EPAC1 activators may therefore act as useful pharmacological tools for elucidation of EPAC function and promising drug leads for the treatment of relevant human diseases.
GLYCOLATE OXIDASE INHIBITORS FOR THE TREATMENT OF DISEASE
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Paragraph 00530; 00531; 00534; 00891; 00892; 00897, (2019/07/17)
Described herein are compounds, methods of making such compounds, pharmaceutical compositions and medicaments containing such compounds, and methods of using such compounds to treat or prevent diseases or disorders associated with the enzyme glycolate oxidase (GO). Such diseases or disorders include, for example, disorders of glyoxylate metabolism, including primary hyperoxaluria, that are associated with production of excessive amounts of oxalate.
Ene Reductase Enzymes for the Aromatisation of Tetralones and Cyclohexenones to Naphthols and Phenols
Kelly, Paul P.,Lipscomb, David,Quinn, Derek J.,Lemon, Ken,Caswell, Jill,Spratt, Jenny,Kosjek, Birgit,Truppo, Matthew,Moody, Thomas S.
supporting information, p. 731 - 736 (2016/03/09)
Ene reductases (EREDs) have great potential as oxidation biocatalysts, as demonstrated by their efficient conversion of a number of tetralones to the corresponding naphthols. Of 96 enzymes tested, 57 were able to produce 2-naphthol in this way. Further tests with substituted tetralones revealed typically high conversions up to >99%. The reactions were performed under mild conditions in aqueous buffer with only co-solvent, biocatalyst and oxidation substrate required for conversion. Production of a methoxy-substituted naphthol was also successfully performed on a gram scale, with 91% yield. This methodology provides a new avenue to produce substituted naphthols as valuable building blocks, with the possibility to extend the approach to the production of phenols also being demonstrated.
Carboxylic acids and acylsulfonamides, compositions containing such compounds and methods of treatment
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, (2008/06/13)
Compounds of formula I: as well as pharmaceutically acceptable salts, hydrates and esters thereof, are disclosed. The compounds are useful for treating or preventing prostaglandin mediated diseases. Pharmaceutical compositions containing such compounds and methods of treatment are also included.
Kinetics and mechanism of ammonolysis and alkaline hydrolysis of naphthyl acetates in aqueous medium: Part II - 6-substituted 2-naphthyl acetates
Ananthakrishna Nadar,Rajarathinam
, p. 342 - 345 (2007/10/03)
Several 6-substituted 2-naphthyl acetates have been prepared and kinetics of their ammonolysis and alkaline hydrolysis studied at 20°, 25° and 30°C at various pH values in water with 1% dioxan at a definite ionic strength. The ammonolysis is first order in [free ammonia] and the process proceeds through a simple unassisted nucleophilic substitution pathway, which includes the zwitterionic tetrahedral intermediate (T±). In no case, is the catalysed pathway visible The reason for the absence of expected-catalysis in the case of ester with methyl substituent is discussed.
