14113-01-0Relevant articles and documents
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Hubbell,W.L.,McConnell,H.M.
, p. 314 - 326 (1971)
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Ni-Catalyzed β-Alkylation of Cyclopropanol-Derived Homoenolates
Mills, L. Reginald,Zhou, Cuihan,Fung, Emily,Rousseaux, Sophie A. L.
, p. 8805 - 8809 (2019/11/03)
Metal homoenolates are valuable synthetic intermediates which provide access to β-functionalized ketones. In this report, we disclose a Ni-catalyzed β-alkylation reaction of cyclopropanol-derived homoenolates using redox-active N-hydroxyphthalimide (NHPI) esters as the alkylating reagents. The reaction is compatible with 1°, 2°, and 3° NHPI esters. Mechanistic studies imply radical activation of the NHPI ester and 2e β-carbon elimination occurring on the cyclopropanol.
Validating Eaton's Hypothesis: Cubane as a Benzene Bioisostere
Chalmers, Benjamin A.,Xing, Hui,Houston, Sevan,Clark, Charlotte,Ghassabian, Sussan,Kuo, Andy,Cao, Benjamin,Reitsma, Andrea,Murray, Cody-Ellen P.,Stok, Jeanette E.,Boyle, Glen M.,Pierce, Carly J.,Littler, Stuart W.,Winkler, David A.,Bernhardt, Paul V.,Pasay, Cielo,De Voss, James J.,McCarthy, James,Parsons, Peter G.,Walter, Gimme H.,Smith, Maree T.,Cooper, Helen M.,Nilsson, Susan K.,Tsanaktsidis, John,Savage, G. Paul,Williams, Craig M.
supporting information, p. 3580 - 3585 (2016/03/23)
Pharmaceutical and agrochemical discovery programs are under considerable pressure to meet increasing global demand and thus require constant innovation. Classical hydrocarbon scaffolds have long assisted in bringing new molecules to the market place, but an obvious omission is that of the Platonic solid cubane. Eaton, however, suggested that this molecule has the potential to act as a benzene bioisostere. Herein, we report the validation of Eaton's hypothesis with cubane derivatives of five molecules that are used clinically or as agrochemicals. Two cubane analogues showed increased bioactivity compared to their benzene counterparts whereas two further analogues displayed equal bioactivity, and the fifth one demonstrated only partial efficacy. Ramifications from this study are best realized by reflecting on the number of bioactive molecules that contain a benzene ring. Substitution with the cubane scaffold where possible could revitalize these systems, and thus expedite much needed lead candidate identification.
PYRIDIN-2YL SULFANYL ACID ESTERS AND PROCESS FOR THE PREPARATION THEREOF
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, (2013/06/04)
The present invention relates to Pyridin-2-yl sulfanyl acid ester compounds having antiinflammatory properties. The present invention particularly relates to novel anti-inflammatory heterocyclic acid esters of Pyridin-2-yl sulfanyl having the structure of general formula 1 which have been screened for their antiinflammatory activity with respect to inhibition of adhesion of neutrophils, isolated from human peripheral blood, onto the surface of human umbilical vein endothelial cells (HU-VEC) as a result of inhibition of the cytokine-stimulated expression of cell adhesion molecule ICAM-1. The compound RS—Z, 3-(Pyridin-2-yl sulfanyl)-propionic acid pentyl ester (structure 1a, R1=H, R2=H, R3=CH2-COOC5H11) was found to be most effective for ICAM-1 and neutrophil adhesion inhibition and was found to effectively alleviate inflammation mediated by excessive leukocyte infiltration leading to inflammatory disorders or like conditions, such as acute lung injury and acute respiratory distress syndrome in mice.
