15357-95-6Relevant academic research and scientific papers
New Dopamine D3-Selective Receptor Ligands Containing a 6-Methoxy-1,2,3,4-tetrahydroisoquinolin-7-ol Motif
Gadhiya, Satishkumar,Cordone, Pierpaolo,Pal, Rajat K.,Gallicchio, Emilio,Wickstrom, Lauren,Kurtzman, Tom,Ramsey, Steven,Harding, Wayne W.
, p. 990 - 995 (2018)
A series of analogues featuring a 6-methoxy-1,2,3,4-tetrahydroisoquinolin-7-ol unit as the arylamine "head" group of a classical D3 antagonist core structure were synthesized and evaluated for affinity at dopamine D1, D2, and D3 receptors (D1R, D2R, D3R). The compounds generally displayed strong affinity for D3R with very good D3R selectivity. Docking studies at D2R and D3R crystal structures revealed that the molecules are oriented such that their arylamine units are positioned in the orthosteric binding pocket of D3R, with the arylamide "tail" units residing in the secondary binding pocket. Hydrogen bonding between Ser 182 and Tyr 365 at D3R stabilize extracellular loop 2 (ECL2), which in turn contributes to ligand binding by interacting with the "tail" units of the ligands in the secondary binding pocket. Similar interactions between ECL2 and the "tail" units were absent at D2R due to different positioning of the D2R loop region. The presence of multiple H-bonds with the phenol moiety of the headgroup of 7 and Ser192 accounts for its stronger D3R affinity as compared to the 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-containing analogue 8.
Synthetic approaches to pallimamine and analogues using direct imine acylation
Ronson, Thomas O.,Kitsiou, Christiana,Unsworth, William P.,Taylor, Richard J.K.
, p. 6099 - 6106 (2016/09/14)
The use of Direct Imine Acylation (DIA) methodology for the total synthesis of pallimamine is described, with three different synthetic routes examined. The construction of three advanced δ-lactam precursors, all utilising DIA, is described, along with attempts to progress these compounds further, using three distinct desymmetrisation strategies, two involving alcohol-aryl coupling, and a third involving an unusual diastereoselective lactonisation.
Formal synthesis of the bisbenzylisoquinoline alkaloid berbamunine by asymmetric substitution of chiral organolithium compounds
Gawley, Robert E.,Smith, Gregory A.
, p. 167 - 179 (2011/07/07)
Asymmetric alkylation of enantiomeric tetrahydroisoquinolyl oxazolines was achieved with 96-97% diastereoselectivity. Removal of the oxazoline chiral auxiliary and further transformations provide a straightforward synthesis of the two synthetic intermediates that were previously synthesized by resolution, and which comprise a formal synthesis of berbamunine by Ullman coupling. ARKAT-USA, Inc.
Synthesis of protoberberines using a silyl-directed Pictet-Spengler cyclization
Cutter, Paul S,Miller, R.Bryan,Schore, Neil E
, p. 1471 - 1478 (2007/10/03)
Five naturally-occurring protoberberines have been synthesized in enantioenriched form by alkylation by two different 2-trimethylsilylbenzyl chlorides of four tetrahydroisoquinolines, derivatized with Meyers' formamidine valinol methyl ether chiral auxiliary. Silyl-directed Pictet-Spengler cyclization of the ensuing 3,4-dimethoxy-2-trimethylsilylbenzyl tetrahydroisoquinolines leads to four of the target protoberberines in excellent yield and complete regioselectivity. In the fifth case, the 3,4-methylenedioxy analog gives a mixture of protoberberine and a product of ring closure at C6 of the benzyl moiety in a 3:4 ratio.
A CONVENIENT SYNTHESIS OF SIMPLE TETRAHYDROISOQUINOLINES
Ruchirawat, S.,Chaisupakitsin, M.,Patranuwatana, N.,Cashaw, J. L.,Davis, V. E.
, p. 1221 - 1228 (2007/10/02)
Various simple tetrahydroisoquinoline alcaloids (Ia,b,c, IIa and IIIa,b,c) have been synthesized by the reaction of appropriate arylethylamines with paraformaldehyde or formaldehyde in formic acid.
