Shonberg, Jeremy; Draper-Joyce, Christopher; Mistry, Shailesh N.; Christopoulos, Arthur; Scammells, Peter J.; Lane, J. Robert; Capuano, Ben published an article in Journal of Medicinal Chemistry. The title of the article was 《Structure-activity study of N-((trans)-4-(2-(7-cyano-3,4-dihydroisoquinolin-2(1H)-yl)ethyl)cyclohexyl)-1H-indole-2-carboxamide (SB269652), a bitopic ligand that acts as a negative allosteric modulator of the dopamine D2 receptor》.Name: 7-Fluoro-1,2,3,4-tetrahydroisoquinoline hydrochloride The author mentioned the following in the article:
The authors recently demonstrated that SB269652 I engages one protomer of a dopamine D2 receptor (D2R) dimer in a bitopic mode to allosterically inhibit the binding of dopamine at the other protomer. Herein, the authors investigate structural determinants for allostery, focusing on modifications to three moieties within I. The authors find that orthosteric “”head”” groups with small 7-substituents were important to maintain the limited neg. cooperativity of analogs of I, and replacement of the tetrahydroisoquinoline head group with other D2R “”privileged structures”” generated orthosteric antagonists. Addnl., replacement of the cyclohexylene linker with polymethylene chains conferred linker length dependency in allosteric pharmacol. The authors validated the importance of the indolic NH as a hydrogen bond donor moiety for maintaining allostery. Replacement of the indole ring with azaindole conferred a 30-fold increase in affinity while maintaining neg. cooperativity. Combined, these results provide novel SAR insight for bitopic ligands that act as neg. allosteric modulators of the D2R. In the experiment, the researchers used 7-Fluoro-1,2,3,4-tetrahydroisoquinoline hydrochloride(cas: 799274-06-9Name: 7-Fluoro-1,2,3,4-tetrahydroisoquinoline hydrochloride)
7-Fluoro-1,2,3,4-tetrahydroisoquinoline hydrochloride(cas: 799274-06-9) belongs to tetrahydroisoquinoline. Tetrahydroisoquinoline Reactions: As a secondary amine, tetrahydroisoquinoline has weakly basic properties and forms salts with strong acids.Name: 7-Fluoro-1,2,3,4-tetrahydroisoquinoline hydrochloride It can be dehydrogenated to give isoquinoline and hydrogenated to decahydroisoquinoline. Like other secondary amines, tetrahydroisoquinoline can be oxidized to the corresponding nitrone using hydrogen peroxide, catalyzed by selenium dioxide.
Referemce:
Tetrahydroisoquinoline – Wikipedia,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem