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A careful exploration of the pharmacophores related to both targets, which in principle had few common characteristics, led to the design of novel compounds exhibiting both activities. The construction of the dual ligands started from published Ca<jats:sub>v<\/jats:sub>\u03b12\u03b4\u20101 ligands, onto which MOR ligand pharmacophoric elements were added. This exercise led to new amino\u2010acidic substances with good affinities on both targets as well as good metabolic and physicochemical profiles and low potential for drug\u2010drug interactions. A representative compound, (2<jats:italic>S<\/jats:italic>,4<jats:italic>S<\/jats:italic>)\u20104\u2010(4\u2010chloro\u20103\u2010(((<jats:italic>cis<\/jats:italic>)\u20104\u2010(dimethylamino)\u20104\u2010phenylcyclohexyl)methyl)\u20105\u2010fluorophenoxy)pyrrolidine\u20102\u2010carboxylic acid, displayed promising analgesic activities in several in\u2005vivo pain models as well as a reduced side\u2010effect profile in relation to morphine.<\/jats:p>","DOI":"10.1002\/cmdc.202300473","type":"journal-article","created":{"date-parts":[[2024,1,17]],"date-time":"2024-01-17T07:49:41Z","timestamp":1705477781000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Towards Multitargeted Ligands as Pain Therapeutics: Dual Ligands of the Ca<sub>v<\/sub>\u03b12\u03b4\u20101\u2009Subunit of Voltage\u2010Gated Calcium Channel and the \u03bc\u2010Opioid 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