115477-28-6Relevant academic research and scientific papers
3-Oxo-hexahydro-1H-isoindole-4-carboxylic Acid as a Drug Chiral Bicyclic Scaffold: Structure-Based Design and Preparation of Conformationally Constrained Covalent and Noncovalent Prolyl Oligopeptidase Inhibitors
Mariaule, Ga?lle,De Cesco, Stéphane,Airaghi, Francesco,Kurian, Jerry,Schiavini, Paolo,Rocheleau, Sylvain,Huski?, Igor,Auclair, Karine,Mittermaier, Anthony,Moitessier, Nicolas
, p. 4221 - 4234 (2016/06/01)
Bicyclic chiral scaffolds are privileged motifs in medicinal chemistry. Over the years, we have reported covalent bicyclic prolyl oligopeptidase inhibitors that were highly selective for POP over a number of homologous proteins. Herein, we wish to report the structure-based design and synthesis of a novel class of POP inhibitors based on hexahydroisoindoles. A docking study guided the selection of structures for synthesis. The stereochemistry, decoration, and position within the molecule of the bicyclic scaffolds were assessed virtually. Following the synthesis of the best candidates, in vitro assays revealed that one member of this chemical series was more active than any of our previous inhibitors with a Ki of 1.0 nM. Additional assays also showed that the scaffold of this potent inhibitor, in contrast to one of our previously reported chemical series, is highly metabolically stable, despite the foreseen potential sites of metabolism. Interestingly, computer docking calculations accurately predicted the optimal features of the inhibitors.
Synthesis of Hydroisoindoles via Intramolecular Diels-Alder Reactions of Functionalised Amido Trienes
Mellor, John M.,Wagland, Alison M.
, p. 997 - 1005 (2007/10/02)
Reactions of amino dienes with acryloyl chloride, maleic anhydride, bromomaleic anhydride, and dichloromaleic anhydride were studied.Acylation and intramolecular reaction by Diels-Alder cyclisation gave bicyclic adducts.Adducts of dichloromaleic anhydride
New features of the intramolecular Diels Alder route to hydroisoindoles
Mellor, John M.,Wagland, Alison M.
, p. 5339 - 5342 (2007/10/02)
Regio- and stereo- controlled routes to functionalised hydroisoindoles have been developed by reaction of aminodienes with unsaturated anhydrides or acid chlorides and subsequent elaboration of the Diels Alder adducts.
