The Oncolytic Efficacy and in Vivo Pharmacokinetics of [2-(4-Chlorophenyl)quinolin-4-yl](piperidine-2-yl)methanol (Vacquinol-1) Are Governed by Distinct Stereochemical Features Show others and affiliations
2016 (English) In: Journal of Medicinal Chemistry, ISSN 0022-2623, E-ISSN 1520-4804, Vol. 59, no 18, p. 8577-8592Article in journal (Refereed) Published
Abstract [en]
Glioblastoma remains an incurable brain cancer. Drugs developed in the past 20 years have not improved the prognosis for patients, necessitating the development of new treatments. We have previously reported the therapeutic potential of the quinoline methanol Vacquinol-1 (1) that targets glioblastoma cells and induces cell death by catastrophic vacuolization. Compound 1 is a mixture of four stereoisomers due to the two adjacent stereogenic centers in the molecule, complicating further development in the preclinical setting. This work describes the isolation and characterization of the individual isomers of 1 and shows that these display stereospecific pharmacokinetic and pharmacodynamic features. In addition, we present a stereoselective synthesis of the active isomers, providing a basis for further development of this compound series into a novel experimental therapeutic for glioblastoma.
Place, publisher, year, edition, pages 2016. Vol. 59, no 18, p. 8577-8592
National Category
Analytical Chemistry
Identifiers URN: urn:nbn:se:ri:diva-13637 DOI: 10.1021/acs.jmedchem.6b01009 Scopus ID: 2-s2.0-84988683885 OAI: oai:DiVA.org:ri-13637 DiVA, id: diva2:1033950
2016-10-102016-10-102025-09-23 Bibliographically approved