109250-11-5Relevant articles and documents
Effect of 1-Substitution on Tetrahydroisoquinolines as Selective Antagonists for the Orexin-1 Receptor
Perrey, David A.,German, Nadezhda A.,Decker, Ann M.,Thorn, David,Li, Jun-Xu,Gilmour, Brian P.,Thomas, Brian F.,Harris, Danni L.,Runyon, Scott P.,Zhang, Yanan
, p. 599 - 614 (2015/04/27)
Selective blockade of the orexin-1 receptor (OX1) has been suggested as a potential approach to drug addiction therapy because of its role in modulating the brain's reward system. We have recently reported a series of tetrahydroisoquinoline-based OX1 selective antagonists. Aimed at elucidating structure-activity relationship requirements in other regions of the molecule and further enhancing OX1 potency and selectivity, we have designed and synthesized a series of analogues bearing a variety of substituents at the 1-position of the tetrahydroisoquinoline. The results show that an optimally substituted benzyl group is required for activity at the OX1 receptor. Several compounds with improved potency and/or selectivity have been identified. When combined with structural modifications that were previously found to improve selectivity, we have identified compound 73 (RTIOX-251) with an apparent dissociation constant (Ke) of 16.1 nM at the OX1 receptor and >620-fold selectivity over the OX2 receptor. In vivo, compound 73 was shown to block the development of locomotor sensitization to cocaine in rats. (Chemical Equation Presented).
Biocatalytic enantioselective oxidative C-C coupling by aerobic C-H activation
Schrittwieser, Joerg H.,Resch, Verena,Sattler, Johann H.,Lienhart, Wolf-Dieter,Durchschein, Katharina,Winkler, Andreas,Gruber, Karl,MacHeroux, Peter,Kroutil, Wolfgang
, p. 1068 - 1071 (2011/04/22)
Bridging the gap: The berberine bridge enzyme (BBE) was employed for the first preparative oxidative biocatalytic C-C coupling that leads to a new intramolecular bond. This unique transformation requires O2 as sole stoichiometric oxidant and gives access to novel optically pure (S)-berbine 2 and (R)-1-benzyl-1,2,3,4-tetrahydroisoquinoline 1 alkaloid derivatives by kinetic resolution.
