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This opioid receptor antagonist pharmacophore was used as a lead structure to design and develop several interesting and useful opioid receptor antagonists. In this review we describe: 1)\u2005early SAR studies that led to the discovery of LY255582 and analogues that are nonselective opioid receptor antagonists developed for the treatment of obesity; 2)\u2005the discovery and commercialization of LY246736 (alvimopan; ENTEREG\u00ae), a peripherally selective opioid receptor antagonist that accelerates the time to upper and lower GI recovery following surgeries that include partial bowel resection with primary anastomosis; and 3)\u2005the discovery and development of the potent and selective \u03ba opioid receptor antagonist JDTic and analogues as potential pharmacotherapies for treating depression, anxiety, and substance abuse (nicotine, alcohol, and cocaine). In addition, the use of JDTic for obtaining the X\u2010ray structure of the human \u03ba opioid receptor is discussed.<\/jats:p>","DOI":"10.1002\/cmdc.201402142","type":"journal-article","created":{"date-parts":[[2014,7,1]],"date-time":"2014-07-01T10:47:57Z","timestamp":1404211677000},"page":"1638-1654","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["The Discovery and Development of the <i>N<\/i>\u2010Substituted <i>trans<\/i>\u20103,4\u2010Dimethyl\u20104\u2010(3\u2032\u2010hydroxyphenyl)piperidine Class of Pure Opioid Receptor Antagonists"],"prefix":"10.1002","volume":"9","author":[{"given":"F. 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