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These included (+)\u2010(1<jats:italic>R<\/jats:italic>,2<jats:italic>R<\/jats:italic>)\u2010U50488, a weak opioid agonist with an EC<jats:sub>50<\/jats:sub> value of 59\u2005n<jats:sc>M<\/jats:sc> as determined in our <jats:italic>T.\u2005brucei<\/jats:italic> in\u2005vitro assay reported previously. This paper describes the modification of key structural elements of U50488 to investigate structure\u2013activity relationships (SAR) and to optimise the antiproliferative activity and pharmacokinetic properties of this compound.<\/jats:p>","DOI":"10.1002\/cmdc.201100278","type":"journal-article","created":{"date-parts":[[2011,8,10]],"date-time":"2011-08-10T09:57:19Z","timestamp":1312970239000},"page":"1832-1840","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Optimisation of the Anti\u2010<i>Trypanosoma brucei<\/i> Activity of the Opioid Agonist U50488"],"prefix":"10.1002","volume":"6","author":[{"given":"Victoria C.","family":"Smith","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura A. 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