215790-43-5

Basic information

• Product Name: trans-2-(2-(1-4-(N-tert-butyloxycarbonyl)amino)cyclohexyl)ethyl-7-cyano-1,2,3,4-tetrahydroisoquinoline
• Synonyms: trans-2-(2-(1-4-(N-tert-butyloxycarbonyl)amino)cyclohexyl)ethyl-7-cyano-1,2,3,4-tetrahydroisoquinoline
• CAS NO: 215790-43-5
• Molecular Weight: 383.534
• Mol File: 215790-43-5.mol
• Article Data: 4

Chemical Properties

• CAS DataBase Reference: trans-2-(2-(1-4-(N-tert-butyloxycarbonyl)amino)cyclohexyl)ethyl-7-cyano-1,2,3,4-tetrahydroisoquinoline(CAS DataBase Reference)
• NIST Chemistry Reference: trans-2-(2-(1-4-(N-tert-butyloxycarbonyl)amino)cyclohexyl)ethyl-7-cyano-1,2,3,4-tetrahydroisoquinoline(215790-43-5)
• EPA Substance Registry System: trans-2-(2-(1-4-(N-tert-butyloxycarbonyl)amino)cyclohexyl)ethyl-7-cyano-1,2,3,4-tetrahydroisoquinoline(215790-43-5)

Safety Data

• Hazardous Substances Data: 215790-43-5(Hazardous Substances Data)

Upstream product

• 149355-52-2 7-cyano-1,2,3,4-tetrahydroisoquinoline 
• 215790-29-7 trans-2-(1-(4-(N-tert-butoxycarbonyl)amino)cyclohexyl)acetaldehyde 
• 76308-28-6 ethyl 2‐[(1r,4r)‐4‐aminocyclohexyl]acetate 
• 104-03-0 4-nitrobenzeneacetic acid 
• 2952-00-3 trans-2-(4-aminocyclohexyl)acetic acid 
• 946598-34-1 trans 2-{1-[4-(N-(tert-butoxycarbonyl))amino]cyclohexyl}ethyl acetate 
• 76308-27-5 trans-4-aminocyclohexylacetic acid methyl ester 
• 61502-37-2 trans-(4-amino)-cyclohexylacetic acid hydrogen sulfate 
• 215789-45-0 trans-2-(1-(4-(N-tert-butoxycarbonyl)amino)cyclohexyl)acetic acid methyl ester 

Downstream Products

• 215802-15-6 SB 269652 

Relevant articles and documents

Subtle Modifications to the Indole-2-carboxamide Motif of the Negative Allosteric Modulator N-((trans)-4-(2-(7-Cyano-3,4-dihydroisoquinolin-2(1 H)-yl)ethyl)cyclohexyl)-1 H-indole-2-carboxamide (SB269652) Yield Dramatic Changes in Pharmacological Activity at the Dopamine D2 Receptor

SB269652 (1) is a negative allosteric modulator of the dopamine D2 receptor. Herein, we present the design, synthesis, and pharmacological evaluation of "second generation" analogues of 1 whereby subtle modifications to the indole-2-carboxamide motif confer dramatic changes in functional affinity (5000-fold increase), cooperativity (100-fold increase), and a novel action to modulate dopamine efficacy. Thus, structural changes to this region of 1 allows the generation of a novel set of analogues with distinct pharmacological properties.

A structure-activity analysis of biased agonism at the dopamine D2 receptor

Biased agonism offers an opportunity for the medicinal chemist to discover pathway-selective ligands for GPCRs. A number of studies have suggested that biased agonism at the dopamine D2 receptor (D2R) may be advantageous for the treatment of neuropsychiatric disorders, including schizophrenia. As such, it is of great importance to gain insight into the SAR of biased agonism at this receptor. We have generated SAR based on a novel D2R partial agonist, tert-butyl (trans-4-(2-(3,4-dihydroisoquinolin- 2(1H)-yl)ethyl)cyclohexyl)carbamate (4). This ligand shares structural similarity to cariprazine (2), a drug awaiting FDA approval for the treatment of schizophrenia, yet displays a distinct bias toward two different signaling end points. We synthesized a number of derivatives of 4 with subtle structural modifications, including incorporation of cariprazine fragments. By combining pharmacological profiling with analytical methodology to identify and to quantify bias, we have demonstrated that efficacy and biased agonism can be finely tuned by minor structural modifications to the head group containing the tertiary amine, a tail group that extends away from this moiety, and the orientation and length of a spacer region between these two moieties.