645388-29-0

Upstream product

• 99-96-7 4-hydroxy-benzoic acid 
• 100-39-0 benzyl bromide 
• 645387-22-0 4-(allyloxy)-N-(3-(benzyloxy)phenethyl)-N-phenylbenzamide 
• 645386-00-1 2-[3-(benzyloxy)phenyl]-N-phenylacetamide 
• 645386-03-4 N-[2-(3-benzyloxyphenyl)ethyl]aniline 
• 59756-83-1 2-(3-(benzyloxy)phenyl)acetyl chloride 
• 36844-51-6 4-allyloxybenzoyl chloride 
• 27914-60-9 4-allyloxybenzoic acid 
• 1860-58-8 3-benzyloxyphenylacetic acid 
• 621-37-4 m-hydroxyphenylacetic acid 
• 645388-17-6 1-(4-allyloxyphenyl)-6-benzyloxy-2-phenyl-3,4-dihydro-1H-isoquinoline 

Downstream Products

• 645399-42-4 6-benzyloxy-2-phenyl-1-[4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-1,2,3,4-tetrahydro-isoquinoline 
• 645399-43-5 6-benzyloxy-2-phenyl-1-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-1,2,3,4-tetrahydro-isoquinoline 

Relevant academic research and scientific papers

TETRAHYDRONAPHTHALENE AND TETRAHYDROISOQUINOLINE DERIVATIVES AS ESTROGEN RECEPTOR DEGRADERS

The present disclosure relates to bifunctional compounds, which find utility as modulators of estrogen receptor (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end at least one of a Von Hippel-Lindau ligand, a cereblon ligand, Inhibitors of Apoptosis Proteins ligand, mouse double-minute homolog 2 ligand, or a combination thereof, which binds to the respective E3 ubiquitin ligase, and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

Estrogen receptor modulators: Identification and structure-activity relationships of potent ERα-selective tetrahydroisoquinoline ligands

As part of a program aimed at the development of selective estrogen receptor modulators (SERMs), tetrahydroisoquinoline derivative 27 was discovered by high throughput screening. Successive replacements of the p-F substituent of 27 by an aminoethoxy side chain and of the 1-H of the tetrahydroisoquinoline core by a 1-Me group provided analogues 19 and 20. These compounds showed potencies in a cell-based reporter gene assay (ERE assay) varying between 0.6 and 20 nM and displayed antagonist behaviors in the MCF-7 human breast adenocarcinoma cell line with IC50s in the range of 2-36 nM. The effect of N-phenyl substituents on the activity and pharmacokinetic properties of tetrahydroisoquinoline analogues was explored. As a result of this investigation, two potent derivatives bearing a p-F N-aryl group, 19c and 20c, were discovered as candidates suitable for further profiling. To gain insight into the ligand-receptor interaction, the X-ray crystallographic structure of the 1-H tetrahydroisoquinoline derivative (R)-18a in complex with ERα-ligand binding domain (LBD)301-553/C→S triple mutant was solved to 2.28 A?. An overlay of this X-ray crystal structure with that reported for the complex of ERαLBD301-553/carboxymethylated C and raloxifene (5) shows that both compounds bind to the same cleft of the receptor and display comparable binding modes, with differences being observed in the conformation of their "D-ring" phenyl groups.