98809-69-9Relevant articles and documents
RHODIUM CATALYZED HYDROGENATION OF NITROGEN HETEROAROMATICS UNDER WATER GAS SHIFT CONDITIONS. SELECTIVE SYNTHESIS OF 1,2,3,4-TETRAHYDROQUINOLINES AND N-FORMYL-1,2,3,4-TETRAHYDROISOQUINOLINES
Murahashi, Shun-Ichi,Imada, Yasushi,Hirai, Yoshiaki
, p. 77 - 80 (1987)
Quinolines and isoquinolines are hydrogenated selectively in the nitrogen-containing ring by means of carbon monoxide and water in the presence of catalytic amount of rhodium carbonyl cluster.
Tetrahydroisoquinolinone-based steroidomimetic and chimeric microtubule disruptors
Leese, Mathew P.,Jourdan, Fabrice L.,Major, Meriel R.,Dohle, Wolfgang,Hamel, Ernest,Ferrandis, Eric,Fiore, Ann,Kasprzyk, Philip G.,Potter, Barry V. L.
, p. 85 - 108 (2014/01/17)
A structure-activity relationship (SAR) translation strategy was used for the discovery of tetrahydroisoquinoline (THIQ)-based steroidomimetic and chimeric microtubule disruptors based upon a steroidal starting point. A steroid A,B-ring-mimicking THIQ core was connected to methoxyaryl D-ring ring mimics through methylene, carbonyl and sulfonyl linkers to afford a number of steroidomimetic hits (e.g., 7-methoxy-2-(3- methoxybenzyl)-6-sulfamoyloxy-1,2,3, 4-tetrahydroisoquinoline (20 c) GI50=2.1 μM). Optimisation and control experiments demonstrate the complementary SAR of this series and the steroid derivatives that inspired its design. Linkage of the THIQ-based A,B-mimic with the trimethoxyaryl motif prevalent in colchicine site binding microtubule disruptors delivered a series of chimeric molecules whose activity (GI50=40 nM) surpasses that of the parent steroid derivatives. Validation of this strategy was obtained from the excellent oral activity of 7-methoxy-6-sulfamoyloxy-2-(3,4,5-trimethoxybenzyl)-1,2,3,4- tetrahydroisoquinoline (20 z) relative to a benchmark steroidal bis- sulfamate Copyright
Chimeric microtubule disruptors
Leese, Mathew P.,Jourdan, Fabrice,Kimberley, Meriel R.,Cozier, Gyles E.,Thiyagarajan, Nethaji,Stengel, Chloe,Regis-Lydi, Sandra,Foster, Paul A.,Newman, Simon P.,Acharya, K. Ravi,Ferrandis, Eric,Purohit, Atul,Reed, Michael J.,Potter, Barry V. L.
supporting information; experimental part, p. 2907 - 2909 (2010/08/04)
A chimeric approach is used to discover microtubule disruptors with excellent in vitro activity and oral bioavailability; a ligand-protein interaction with carbonic anhydrase that enhances bioavailability is characterised by protein X-ray crystallography. Dosing of a representative chimera in a tumour xenograft model confirms the excellent therapeutic potential of the class. The Royal Society of Chemistry 2010.
