Synthesis and Structure–Activity Relationships of Triazaspirodecanone Derivatives as Nociceptin/Orphanin FQ Receptor Ligands. (20th January 2015)

• Record Type: Journal Article
• Authors: Corrado, Sandra; Battisti, Umberto M.; Sorbi, Claudia; Tait, Annalisa; Malfacini, Davide; Camarda, Valeria; Calò, Girolamo; Brasili, Livio
• Is Part Of: Chemical biology & drug design. Volume 86:Number 4(2015:Oct.)
• Page Start: 447
• Page End: 458
• Publication Date: 2015-01-20
• Subjects: Drugs -- Design -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; 615.19005
• DOI: 10.1111/cbdd.12505
• Languages: English
• ISSNs: 1747-0277

Abstract

<abstract abstract-type="main" id="cbdd12505-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Several spiroxatrine derivatives were synthesized and evaluated as potential NOP receptor ligands. Structural modifications of the 1, 4‐benzodioxane moiety of spiroxatrine have been the focus of this research project. The structure–activity relationships that emerged indicate that the presence of an <italic>H‐bond donor group</italic> (hydroxyl group) is more favorable for NOP activity when it is positioned α with respect to the CH₂ linked to the 1‐phenyl‐1, 3, 8‐triaza‐spiro[4.5]decan‐4‐one portion. Moreover, <italic>cis</italic> diastereoisomers of the <italic>hydroxyl derivatives</italic><bold>4</bold> and <bold>22</bold> show a moderately higher degree of stereoselectivity than <italic>trans</italic> isomers. In particular, the spiropiperidine derivative <italic><bold>cis</bold></italic>‐<bold>4</bold> has submicromolar agonistic activity, and it will be the reference compound for the design and synthesis of new NOP agonists.</p> </abstract>