| Literature DB >> 30457865 |
Ana Guardia1, Jessica Baiget2, Mónica Cacho1, Arancha Pérez1, Montserrat Ortega-Guerra1, Winston Nxumalo1, Setshaba D Khanye1, Joaquín Rullas1, Fátima Ortega1, Elena Jiménez1, Esther Pérez-Herrán1, María Teresa Fraile-Gabaldón1, Jorge Esquivias1, Raquel Fernández1, Esther Porras-De Francisco1, Lourdes Encinas1, Marta Alonso1, Ilaria Giordano1, Cristina Rivero1, Juan Miguel-Siles1, Javier G Osende2, Katrina A Badiola2, Peter J Rutledge2, Matthew H Todd2,3, Modesto Remuiñán1, Carlos Alemparte1.
Abstract
Society urgently needs new, effective medicines for the treatment of tuberculosis. To kick-start the required hit-to-lead campaigns, the libraries of pharmaceutical companies have recently been evaluated for starting points. The GlaxoSmithKline (GSK) library yielded many high-quality hits, and the associated data were placed in the public domain to stimulate engagement by the wider community. One such series, the spiro compounds, are described here. The compounds were explored by a combination of traditional in-house research and open source methods. The series benefits from a particularly simple structure and a short associated synthetic chemistry route. Many members of the series displayed striking potency and low toxicity, and highly promising in vivo activity in a mouse model was confirmed with one of the analogues. Ultimately the series was discontinued due to concerns over safety, but the associated data remain public domain, empowering others to resume the series if the perceived deficiencies can be overcome.Entities:
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Year: 2018 PMID： 30457865 DOI： 10.1021/acs.jmedchem.8b01533
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446