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Recently, their use as E3 ligase recruiting elements for small\u2010molecule\u2010induced protein degradation has led to a resurgence in interest in IMiD synthesis and functionalization. Traditional IMiD synthesis follows a stepwise route with multiple purification steps. Herein we describe a novel one\u2010pot synthesis without purification that provides rapid access to a multitude of IMiD analogues. Binding studies with the IMiD target protein cereblon (CRBN) reveals a narrow structure\u2013activity relationship with only a few compounds showing sub\u2010micromolar binding affinity in the range of pomalidomide and lenalidomide. However, anti\u2010proliferative activity as well as Aiolos degradation could be identified for two IMiD analogues. This study provides useful insight into the structure\u2013degradation relationships for molecules of this type as well as a rapid and robust method for IMiD synthesis.<\/jats:p>","DOI":"10.1002\/cmdc.201800271","type":"journal-article","created":{"date-parts":[[2018,6,5]],"date-time":"2018-06-05T12:08:07Z","timestamp":1528200487000},"page":"1508-1512","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Efficient Synthesis of Immunomodulatory Drug Analogues Enables Exploration of Structure\u2013Degradation Relationships"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2812-983X","authenticated-orcid":false,"given":"George M.","family":"Burslem","sequence":"first","affiliation":[{"name":"Department of Molecular, Cellular and Developmental Biology Yale University  219 Prospect Street New Haven CT 06520-8103 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