Synthetic Route of 82771-60-6, The reaction rate of a catalyzed reaction is faster than the reaction rate of the uncatalyzed reaction at the same temperature.82771-60-6, Name is 7-Chloro-1,2,3,4-tetrahydroisoquinoline, molecular formula is C9H10ClN. In a Article£¬once mentioned of 82771-60-6
Structure-Activity Study of N -((trans)-4-(2-(7-Cyano-3,4-dihydroisoquinolin-2(1 H)-yl)ethyl)cyclohexyl)-1 H -indole-2-carboxamide (SB269652), a Bitopic Ligand That Acts as a Negative Allosteric Modulator of the Dopamine D2 Receptor
We recently demonstrated that SB269652 (1) 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, we investigate structural determinants for allostery, focusing on modifications to three moieties within 1. We find that orthosteric “head” groups with small 7-substituents were important to maintain the limited negative cooperativity of analogues of 1, and replacement of the tetrahydroisoquinoline head group with other D2R “privileged structures” generated orthosteric antagonists. Additionally, replacement of the cyclohexylene linker with polymethylene chains conferred linker length dependency in allosteric pharmacology. We 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 negative cooperativity. Combined, these results provide novel SAR insight for bitopic ligands that act as negative allosteric modulators of the D2R.
We¡¯ll also look at important developments in the pharmaceutical industry because understanding organic chemistry is important in understanding health, medicine, the role of 82771-60-6, and how the biochemistry of the body works.Synthetic Route of 82771-60-6
Reference£º
Tetrahydroisoquinoline – Wikipedia,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem